Posttraumatic stress disorder (PTSD) is a syndrome that occurs after exposure to a significant traumatic event and is characterized by persistent, debilitating symptoms that fall into four “diagnostic clusters” as outlined in the Diagnostic and Statistical Manual of Mental Disorders-Version V (DSM-V). Patients may experience intrusive thoughts, avoidance of distressing stimuli, persistent negative mood, and hypervigilance, all of which last longer than 1 month.¹

A national survey of United States households conducted during 2001-2003 estimated the 12-month prevalence of PTSD among adults to be 3.5%.² Lifetime prevalence has been found to be between 6.8%³ and 7.8%.⁴ PTSD is more common in veterans. The prevalence of PTSD in veterans differs depending on the conflict in which the veteran participated. Vietnam veterans have an estimated lifetime prevalence of approximately 30%,^5,6 Gulf War veterans approximately 15%,⁷ and veterans of more recent conflicts in Afghanistan and Iraq of approximately 21%.⁸ With the MISSION Act moving more veteran care into the private sector, non-VA inpatient providers will need to become better versed in PTSD.⁹

Patients with PTSD have more contact with the healthcare system, even for non–mental health problems,^8,10-13 and a significantly higher burden of medical comorbities,¹⁴ such as diabetes mellitus, liver disease, gastritis and gastric ulcers, HIV, arthritis,¹⁵ and coronary heart disease.¹⁶ Veterans with PTSD are hospitalized three times more often than are those with no mental health diagnoses,⁸ and patients with psychiatric comorbidities have higher lengths of stay.¹⁷ More than 1.4 million hospitalizations occurring during 2002-2011 had either a primary or secondary associated diagnosis of PTSD, with total inflation-­adjusted charges of 34.9 billion dollars.¹⁸ In the inpatient sample from this study, greater than half were admitted for a primary diagnosis of mental diseases and disorders (Major Diagnostic Category [MDC] 19). Following mental illness, the most common primary diagnoses for men were MDC 5 (Circulatory System, 12.1%), MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 9.2%), and MDC 4 (Respiratory System, 7.4%), while the most common categories for women were MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 5.8%), MDC 21 (Injuries, Poison, and Toxic Effect of Drugs, 4.9%), and MDC 6 (Digestive System, 4.5%).¹⁸

In both the inpatient and outpatient settings, a fundamental challenge to comprehensive PTSD management is correctly diagnosing this condition.¹⁹ Confounding the difficulties in diagnosis are numerous comorbidities. In addition to the physical comorbidities described above, more than 70% of patients with PTSD have another psychological comorbidity such as affective disorders, anxiety disorders, or substance use disorder/dependency.²⁰

Given that PTSD may be an underrecognized burden on the healthcare system, we sought to better understand how PTSD could affect hospitalized patients admitted for medical problems by conducting this narrative review. Additionally, three of the authors collaborated with the VA Employee Education Service to conduct a needs assessment of VA hospitalists in 2013. Respondents identified managing and educating patients and families about PTSD as a major educational need (unpublished data available upon request from the corresponding author). Therefore, our aims were to present a synthesis of existing literature, familiarize readers with the tenets of trauma-­informed care as a framework to guide care for these patients, and generate ideas for changes that inpatient providers could implement now. We began by consulting a research librarian at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin, who searched the following databases: PsycInfo, CINAHL, MEDLINE, and PILOTS (a PTSD/trauma specific database). Search terms included hospital, hospitalized, and hospitalization, as well as traumatic stress, posttraumatic stress, and PTSD. Pertinent guidelines and the reference lists from included papers were examined. We focused on papers that described patients admitted for medical problems other than PTSD because those patients who are admitted for PTSD-­related problems should be primarily ma­naged by psychiatry (not hospitalists) with the primary focus of their hospitalization being their PTSD. We also excluded papers about patients developing PTSD secondary to hospitalization, which already has a well-developed literature.^21-23

The literature is sparse describing frequency or type of problems encountered by hospitalized medical patients with PTSD. A recent small survey study reported that 40% of patients anticipated triggers for their PTSD symptoms in the hospital; such triggers included loud noises and being shaken awake.²⁴ Two papers describe case vignettes of patients who had exacerbations of their PTSD while in the Intensive Care Unit (ICU), although neither contain frequency or severity data.^25,26 Approximately 8% of patients in VA ICUs have PTSD,²⁷ and a published abstract suggests that they appear to require more sedation than do patients without PTSD.²⁸ Another published case report describes a patient with recurrent PTSD symptoms (nightmares) after moving into a nursing home.²⁹ These papers suggest other providers have recognized and are concerned about hospitalized patients with PTSD. At present, there are no data to quantify how often hospitalized patients have PTSD exacerbations or how troublesome such exacerbations are to these patients.

Given that there is little empiric literature to guide inpatient management of PTSD as a comorbidity in hospitalized medical patients, we extrapolate some information from the outpatient setting. PTSD is often underdiagnosed and underreported by individual patients in the outpatient setting.³⁰ Failure to have an associated diagnosis of PTSD may lead to underrecognition and undertreatment of these patients by inpatient providers in the hospital setting. Additionally, the numerous psychological and physical comorbidities in PTSD can create unique challenges in properly managing any single problem in these patients.²⁰ Armed with this knowledge, providers should be vigilant in the recognition, assessment, and treatment of PTSD.

Trauma-Informed Care: A Conceptual Model

Trauma-informed care is a mindful and sensitive approach to caring for patients who have suffered trauma.³¹ It requires understanding that many people have suffered trauma in their lives and that the trauma continues to impact many aspects of their lives.³² Trauma-informed care has many advocates and has been implemented across myriad health and social services settings.³³ Its principles can be applied in both the inpatient and outpatient hospital settings. While it is an appropriate approach to patients with PTSD, it is not specific to PTSD. People who have suffered sexual trauma, intimate partner violence, child abuse, or other exposures would also be included in the group of people for whom trauma-informed care is a suitable approach. There are four key assumptions to a trauma-­informed approach to care (the 4 R’s): (1) realization that trauma affects an individual’s coping strategies, relationships, and health; (2) recognition of the signs of trauma; (3) having an appropriate, planned response to patients identified as having suffered a trauma; and (4) resisting retraumatization in the care setting.^31,32

General Approach to Treating Medical Patients With PTSD in the Inpatient Setting

Recognition

Consistent with a trauma-informed care approach, inpatient providers should be able to recognize patients who may have PTSD. First, careful review of the past medical history may show some patients already carry this diagnosis. Second, patients with PTSD often have other comorbidities that could offer a clue that PTSD could be present as well; for example, risk for PTSD is increased when mood, anxiety, or substance use disorders are present.²⁰ When PTSD is suspected, screening is a reasonable next step.

The Primary Care-PTSD-5 (PC-PTSD-5) is a validated screening tool used in the outpatient setting.³⁴ It is easily administered and has good predictive validity (positive likelihood ratio [LR+] of 6.33 and LR– of 0.06). It begins with a question of whether the patient has ever experienced a trauma. A positive initial response triggers a series of five yes/no questions. Answering “yes” to three or more questions is a positive screen. A positive screen should result in consultation to psychiatry to conduct more formal evaluation and guide longer-term management.

Collaboration

Individual trauma-focused psychotherapy is the primary treatment of choice for PTSD with strong evidence supporting its practice.³⁵ This treatment is administered by a psychiatrist or psychologist and will be limited in the inpatient medical setting. Current recommendations suggest pharmacotherapy only when individualized trauma-focused psychotherapy is not available, the patient declines it, or as an adjunct when psychotherapy alone is not effective.³⁶ Therefore, inpatient providers may see patients who are prescribed selective serotonin reuptake inhibitors (eg, paroxetine, fluoxetine) or serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine).³⁶ In the past, PTSD-related nightmares were often treated with prazosin.³⁷ However, a recent randomized controlled trial of prazosin in veterans with PTSD failed to show significant improvement in nightmares.³⁸ Hence, current guidelines do not recommend prazosin as a first-line therapy.³⁹ For hospitalized patients with PTSD symptoms refractory to the interventions outlined herein, particularly those patients with possible borderline personality traits (as suggested by severe anger and impulsivity), we strongly recommend partnering with psychiatry. Finally, given the high prevalence of substance use disorders (SUDs) in PTSD patients, awareness and treatment of comorbidities such as opioid and alcohol dependence must be concurrently addressed.

Individualizing Care

It is essential for the healthcare team to identify ways to meet each patient’s immediate needs. Many of the ideas proposed below are not specific to PTSD; many require an interprofessional approach to care.⁴⁰ From a trauma-informed care standpoint, this is akin to having a planned response for patients who have suffered trauma. Assessing the individual’s needs and incorporating therapeutic modalities such as reflective listening, broadening safe opportunities for control, and providing complementary and integrative medicine (IM) therapies may help manage symptoms and establish rapport.⁴¹ Through reflective listening, a collaborative approach can be established to identify background, triggers, and a safe approach for managing PTSD and its comorbid conditions. Ensuring frequent communication and allowing the patient to be at the center of decision-making establishes a safe environment and promotes positive rapport between the patient and healthcare team.³⁶ Providing a sense of control by involving the patients in their healthcare decisions and in the structure of care delivery may benefit the patients’ well-being. Furthermore, incorporating IM encourages rest and relaxation in the chaotic hospital environment. Suggested IM interventions include deep breathing, aromatherapy, guided imagery, muscle relaxation, and music therapy.^42,43

Key Inpatient Issues Affecting PTSD

In the following sections, we outline common clinical situations that may exacerbate PTSD symptoms and propose some evidence-based responses (Table). In general, nonpharmacologic approaches are favored over pharmacologic approaches for patients with PTSD.

Sleep Hygiene

Sleep problems are very common in patients with PTSD, with nightmares occurring in more than 70% of patients and insomnia in 80%.⁴⁴ In PTSD, sleep problems are linked to poor physical health and other health outcomes^45,46 and may exacerbate other PTSD symptoms.⁴

Treating the sleep problems that occur with PTSD is an important aspect of PTSD care. Usually administered in the outpatient setting, the treatment of choice is cognitive-behavioral therapy (CBT).⁴⁸ Sleep-specific CBT focuses, among other things, on strategies that encourage good sleep hygiene,⁴⁹ which includes promoting regular sleep/wake-up times and specific bedtime routines, avoiding stimulation (eg, light, noise, TV) or excessive liquids before bed, refraining from daytime naps, and using relaxation techniques. Many of these recommendations seem at odds with hospital routines, which may contribute to decompensation of hospitalized patients with PTSD.

While starting sleep-specific CBT in the hospital may not be realistic, we suggest the following goals and strategies as a starting place for promoting healthy sleep for hospitalized patients with PTSD. To begin, factors affecting sleep hygiene should be addressed. Inpatient providers could pay more attention to intravenous (IV) fluid orders, perhaps adjusting them to run only during the daytime hours. Medications can be scheduled at times conducive to maintaining home routines. Avoiding the administration of diuretics close to bedtime may decrease the likelihood of frequent nighttime wakening. Grouping patient care activities, such as bathing or wound care, during daytime hours may allow more opportunities for rest at night. Incorporating uninterrupted sleep protocols, such as quiet hours between 10pm and 6am, may enhance sleep quality in the appropriately selected patient.⁵⁰ Although pharmacological interventions to improve sleep in the hospital may be initially beneficial, nonpharmacological interventions as described above should be incorporated for long-term maintenance of enhanced sleep quality.

Second, providers need to ask about established home bedtime routines and facilitate implementation in the hospital. Through collaboration with patients, providers can incorporate an individualized plan of care for sleep early in hospitalization.⁵⁰ Partnering with nurses is also essential to creating a sleep-friendly environment that can improve patient experiences.⁵¹ Breathing exercises, meditating, listening to music and praying are all examples of “bedtime wind down” strategies recommended in sleep-specific CBT.⁴⁹ Many of these could be successfully implemented in the hospital and may benefit other hospitalized patients too.⁵² In patients with PTSD and obstructive sleep apnea, continuous positive airway pressure (CPAP) reduces nightmares, and if inpatients are on CPAP at home, it should be continued in the hospital.⁵³

Pain

If sleep disturbance is the hallmark of PTSD,⁴⁷ chronic pain is its coconspirator.¹⁵ Uncontrolled pain can make it much more difficult to treat patients with PTSD, which in turn may lead to further decompensation from a mental health standpoint.⁵⁴ SUDs such as alcohol or opioid dependencies are highly comorbid with PTSD⁴⁵ and introduce a layer of complexity when managing painin these patients. Providers should be thoughtful when electing to treat acute or chronic pain with opioids and take particular care to establish realistic therapeutic goals if doing so. While patients with PTSD have a greater likelihood of having an SUD, undertreating pain risks exacerbating underlying PTSD symptoms.

Nonpharmacologic therapies, which include communicating, listening, and expressing compassion and understanding, should be utilized by inpatient providers as a first-line treatment in patients with PTSD who suffer from pain. Additionally, relaxation techniques, physical therapy, and physical activity⁵⁵ can be offered. Pharmacologically, nonopioid medications such as acetaminophen or NSAIDs should always be considered first. Should the use of opioids be deemed necessary, inpatient providers should preferentially use oral over intravenous medications and consider establishing a fixed timeframe for short-term opioids, which should be limited to a few days. Providers should communicate clear expectations with their patients to maximize the desired effect of any specific treatment while minimizing the risk of medication side effects with the goal of agreeing on a short yet effective treatment course.

Anxiety and Anger

One of the most challenging situations for the inpatient provider is encountering a patient who is anxious, angry, or hypervigilant. Mismatch between actual and expected communication between the provider and the patient can lead to frustration and anxiety. A trauma-informed care approach would suggest that frequent and thorough communication with patients may prevent or ameliorate the stresses and anxieties of hospitalization that may manifest as anger because of retraumatization. Hospitalizations usually lead to disruption of normal routine (eg, unpredictable meal times or medication administration), interrupted sleep (eg, woken up for blood draws or provider evaluation), and lack of control of schedule (eg, unsure of exact time when a procedure may be occurring), any of which may trigger symptoms of anxiety and anger in patients with PTSD and lead to hypervigilance.

If situations involving patient anxiety do arise, employ compassion and communication. Extra time spent with the patient, while challenging in the hectic hospital environment, is critical, and nonpharmacological treatments should be the priority. Engaging patients by asking about their PTSD triggers²⁴ may help prevent exacerbations. For example, some patients may specify how they prefer to be woken up to prevent startle reactions. PTSD triggers can be reduced via effective communication with the entire healthcare team. Some immediate yet effective strategies are listening, validation, and negotiation. Benzodiazepine or antipsychotic usage should be avoided.³⁶ Inpatient social work and comanagement with psychiatry involvement may be helpful in more severe exacerbations. A small observational study of patients hospitalized for severe PTSD found an association between walking more during hospitalization and fewer PTSD symptoms,⁵⁶ suggesting that staying active could be helpful for inpatients with PTSD who are able to safely ambulate.

PTSD is a common comorbidity among hospitalized patients in the United States. Typical hospital routines may exacerbate symptoms of PTSD such as anxiety and anger. Inpatient providers can play an important role in making hospitalizations go more smoothly for these patients by using principles consistent with trauma-informed care. Specifically, partnering with patients to construct a plan that preserves their sleep routines and accounts for potential triggers for decompensation can improve the hospital experience for patients with PTSD. Some PTSD interventions require additional investment from the healthcare system to deploy, such as staff training in trauma-­informed care and reflective listening techniques. Electronic health record–based protocols and order sets for patients with PTSD can leverage available resources. Further research should evaluate hospital outcomes that result from a more tailored approach to the care of patients with PTSD. More effective, patient-centered PTSD care could lower rates of leaving against medical advice and improve the inpatient experience for patients and providers alike.

Posttraumatic stress disorder (PTSD) is a syndrome that occurs after exposure to a significant traumatic event and is characterized by persistent, debilitating symptoms that fall into four “diagnostic clusters” as outlined in the Diagnostic and Statistical Manual of Mental Disorders-Version V (DSM-V). Patients may experience intrusive thoughts, avoidance of distressing stimuli, persistent negative mood, and hypervigilance, all of which last longer than 1 month.¹

A national survey of United States households conducted during 2001-2003 estimated the 12-month prevalence of PTSD among adults to be 3.5%.² Lifetime prevalence has been found to be between 6.8%³ and 7.8%.⁴ PTSD is more common in veterans. The prevalence of PTSD in veterans differs depending on the conflict in which the veteran participated. Vietnam veterans have an estimated lifetime prevalence of approximately 30%,^5,6 Gulf War veterans approximately 15%,⁷ and veterans of more recent conflicts in Afghanistan and Iraq of approximately 21%.⁸ With the MISSION Act moving more veteran care into the private sector, non-VA inpatient providers will need to become better versed in PTSD.⁹

Patients with PTSD have more contact with the healthcare system, even for non–mental health problems,^8,10-13 and a significantly higher burden of medical comorbities,¹⁴ such as diabetes mellitus, liver disease, gastritis and gastric ulcers, HIV, arthritis,¹⁵ and coronary heart disease.¹⁶ Veterans with PTSD are hospitalized three times more often than are those with no mental health diagnoses,⁸ and patients with psychiatric comorbidities have higher lengths of stay.¹⁷ More than 1.4 million hospitalizations occurring during 2002-2011 had either a primary or secondary associated diagnosis of PTSD, with total inflation-­adjusted charges of 34.9 billion dollars.¹⁸ In the inpatient sample from this study, greater than half were admitted for a primary diagnosis of mental diseases and disorders (Major Diagnostic Category [MDC] 19). Following mental illness, the most common primary diagnoses for men were MDC 5 (Circulatory System, 12.1%), MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 9.2%), and MDC 4 (Respiratory System, 7.4%), while the most common categories for women were MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 5.8%), MDC 21 (Injuries, Poison, and Toxic Effect of Drugs, 4.9%), and MDC 6 (Digestive System, 4.5%).¹⁸

In both the inpatient and outpatient settings, a fundamental challenge to comprehensive PTSD management is correctly diagnosing this condition.¹⁹ Confounding the difficulties in diagnosis are numerous comorbidities. In addition to the physical comorbidities described above, more than 70% of patients with PTSD have another psychological comorbidity such as affective disorders, anxiety disorders, or substance use disorder/dependency.²⁰

Given that PTSD may be an underrecognized burden on the healthcare system, we sought to better understand how PTSD could affect hospitalized patients admitted for medical problems by conducting this narrative review. Additionally, three of the authors collaborated with the VA Employee Education Service to conduct a needs assessment of VA hospitalists in 2013. Respondents identified managing and educating patients and families about PTSD as a major educational need (unpublished data available upon request from the corresponding author). Therefore, our aims were to present a synthesis of existing literature, familiarize readers with the tenets of trauma-­informed care as a framework to guide care for these patients, and generate ideas for changes that inpatient providers could implement now. We began by consulting a research librarian at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin, who searched the following databases: PsycInfo, CINAHL, MEDLINE, and PILOTS (a PTSD/trauma specific database). Search terms included hospital, hospitalized, and hospitalization, as well as traumatic stress, posttraumatic stress, and PTSD. Pertinent guidelines and the reference lists from included papers were examined. We focused on papers that described patients admitted for medical problems other than PTSD because those patients who are admitted for PTSD-­related problems should be primarily ma­naged by psychiatry (not hospitalists) with the primary focus of their hospitalization being their PTSD. We also excluded papers about patients developing PTSD secondary to hospitalization, which already has a well-developed literature.^21-23

The literature is sparse describing frequency or type of problems encountered by hospitalized medical patients with PTSD. A recent small survey study reported that 40% of patients anticipated triggers for their PTSD symptoms in the hospital; such triggers included loud noises and being shaken awake.²⁴ Two papers describe case vignettes of patients who had exacerbations of their PTSD while in the Intensive Care Unit (ICU), although neither contain frequency or severity data.^25,26 Approximately 8% of patients in VA ICUs have PTSD,²⁷ and a published abstract suggests that they appear to require more sedation than do patients without PTSD.²⁸ Another published case report describes a patient with recurrent PTSD symptoms (nightmares) after moving into a nursing home.²⁹ These papers suggest other providers have recognized and are concerned about hospitalized patients with PTSD. At present, there are no data to quantify how often hospitalized patients have PTSD exacerbations or how troublesome such exacerbations are to these patients.

Given that there is little empiric literature to guide inpatient management of PTSD as a comorbidity in hospitalized medical patients, we extrapolate some information from the outpatient setting. PTSD is often underdiagnosed and underreported by individual patients in the outpatient setting.³⁰ Failure to have an associated diagnosis of PTSD may lead to underrecognition and undertreatment of these patients by inpatient providers in the hospital setting. Additionally, the numerous psychological and physical comorbidities in PTSD can create unique challenges in properly managing any single problem in these patients.²⁰ Armed with this knowledge, providers should be vigilant in the recognition, assessment, and treatment of PTSD.

Trauma-Informed Care: A Conceptual Model

Trauma-informed care is a mindful and sensitive approach to caring for patients who have suffered trauma.³¹ It requires understanding that many people have suffered trauma in their lives and that the trauma continues to impact many aspects of their lives.³² Trauma-informed care has many advocates and has been implemented across myriad health and social services settings.³³ Its principles can be applied in both the inpatient and outpatient hospital settings. While it is an appropriate approach to patients with PTSD, it is not specific to PTSD. People who have suffered sexual trauma, intimate partner violence, child abuse, or other exposures would also be included in the group of people for whom trauma-informed care is a suitable approach. There are four key assumptions to a trauma-­informed approach to care (the 4 R’s): (1) realization that trauma affects an individual’s coping strategies, relationships, and health; (2) recognition of the signs of trauma; (3) having an appropriate, planned response to patients identified as having suffered a trauma; and (4) resisting retraumatization in the care setting.^31,32

General Approach to Treating Medical Patients With PTSD in the Inpatient Setting

Recognition

Consistent with a trauma-informed care approach, inpatient providers should be able to recognize patients who may have PTSD. First, careful review of the past medical history may show some patients already carry this diagnosis. Second, patients with PTSD often have other comorbidities that could offer a clue that PTSD could be present as well; for example, risk for PTSD is increased when mood, anxiety, or substance use disorders are present.²⁰ When PTSD is suspected, screening is a reasonable next step.

The Primary Care-PTSD-5 (PC-PTSD-5) is a validated screening tool used in the outpatient setting.³⁴ It is easily administered and has good predictive validity (positive likelihood ratio [LR+] of 6.33 and LR– of 0.06). It begins with a question of whether the patient has ever experienced a trauma. A positive initial response triggers a series of five yes/no questions. Answering “yes” to three or more questions is a positive screen. A positive screen should result in consultation to psychiatry to conduct more formal evaluation and guide longer-term management.

Collaboration

Individual trauma-focused psychotherapy is the primary treatment of choice for PTSD with strong evidence supporting its practice.³⁵ This treatment is administered by a psychiatrist or psychologist and will be limited in the inpatient medical setting. Current recommendations suggest pharmacotherapy only when individualized trauma-focused psychotherapy is not available, the patient declines it, or as an adjunct when psychotherapy alone is not effective.³⁶ Therefore, inpatient providers may see patients who are prescribed selective serotonin reuptake inhibitors (eg, paroxetine, fluoxetine) or serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine).³⁶ In the past, PTSD-related nightmares were often treated with prazosin.³⁷ However, a recent randomized controlled trial of prazosin in veterans with PTSD failed to show significant improvement in nightmares.³⁸ Hence, current guidelines do not recommend prazosin as a first-line therapy.³⁹ For hospitalized patients with PTSD symptoms refractory to the interventions outlined herein, particularly those patients with possible borderline personality traits (as suggested by severe anger and impulsivity), we strongly recommend partnering with psychiatry. Finally, given the high prevalence of substance use disorders (SUDs) in PTSD patients, awareness and treatment of comorbidities such as opioid and alcohol dependence must be concurrently addressed.

Individualizing Care

It is essential for the healthcare team to identify ways to meet each patient’s immediate needs. Many of the ideas proposed below are not specific to PTSD; many require an interprofessional approach to care.⁴⁰ From a trauma-informed care standpoint, this is akin to having a planned response for patients who have suffered trauma. Assessing the individual’s needs and incorporating therapeutic modalities such as reflective listening, broadening safe opportunities for control, and providing complementary and integrative medicine (IM) therapies may help manage symptoms and establish rapport.⁴¹ Through reflective listening, a collaborative approach can be established to identify background, triggers, and a safe approach for managing PTSD and its comorbid conditions. Ensuring frequent communication and allowing the patient to be at the center of decision-making establishes a safe environment and promotes positive rapport between the patient and healthcare team.³⁶ Providing a sense of control by involving the patients in their healthcare decisions and in the structure of care delivery may benefit the patients’ well-being. Furthermore, incorporating IM encourages rest and relaxation in the chaotic hospital environment. Suggested IM interventions include deep breathing, aromatherapy, guided imagery, muscle relaxation, and music therapy.^42,43

Key Inpatient Issues Affecting PTSD

In the following sections, we outline common clinical situations that may exacerbate PTSD symptoms and propose some evidence-based responses (Table). In general, nonpharmacologic approaches are favored over pharmacologic approaches for patients with PTSD.

Sleep Hygiene

Sleep problems are very common in patients with PTSD, with nightmares occurring in more than 70% of patients and insomnia in 80%.⁴⁴ In PTSD, sleep problems are linked to poor physical health and other health outcomes^45,46 and may exacerbate other PTSD symptoms.⁴

Treating the sleep problems that occur with PTSD is an important aspect of PTSD care. Usually administered in the outpatient setting, the treatment of choice is cognitive-behavioral therapy (CBT).⁴⁸ Sleep-specific CBT focuses, among other things, on strategies that encourage good sleep hygiene,⁴⁹ which includes promoting regular sleep/wake-up times and specific bedtime routines, avoiding stimulation (eg, light, noise, TV) or excessive liquids before bed, refraining from daytime naps, and using relaxation techniques. Many of these recommendations seem at odds with hospital routines, which may contribute to decompensation of hospitalized patients with PTSD.

While starting sleep-specific CBT in the hospital may not be realistic, we suggest the following goals and strategies as a starting place for promoting healthy sleep for hospitalized patients with PTSD. To begin, factors affecting sleep hygiene should be addressed. Inpatient providers could pay more attention to intravenous (IV) fluid orders, perhaps adjusting them to run only during the daytime hours. Medications can be scheduled at times conducive to maintaining home routines. Avoiding the administration of diuretics close to bedtime may decrease the likelihood of frequent nighttime wakening. Grouping patient care activities, such as bathing or wound care, during daytime hours may allow more opportunities for rest at night. Incorporating uninterrupted sleep protocols, such as quiet hours between 10pm and 6am, may enhance sleep quality in the appropriately selected patient.⁵⁰ Although pharmacological interventions to improve sleep in the hospital may be initially beneficial, nonpharmacological interventions as described above should be incorporated for long-term maintenance of enhanced sleep quality.

Second, providers need to ask about established home bedtime routines and facilitate implementation in the hospital. Through collaboration with patients, providers can incorporate an individualized plan of care for sleep early in hospitalization.⁵⁰ Partnering with nurses is also essential to creating a sleep-friendly environment that can improve patient experiences.⁵¹ Breathing exercises, meditating, listening to music and praying are all examples of “bedtime wind down” strategies recommended in sleep-specific CBT.⁴⁹ Many of these could be successfully implemented in the hospital and may benefit other hospitalized patients too.⁵² In patients with PTSD and obstructive sleep apnea, continuous positive airway pressure (CPAP) reduces nightmares, and if inpatients are on CPAP at home, it should be continued in the hospital.⁵³

Pain

If sleep disturbance is the hallmark of PTSD,⁴⁷ chronic pain is its coconspirator.¹⁵ Uncontrolled pain can make it much more difficult to treat patients with PTSD, which in turn may lead to further decompensation from a mental health standpoint.⁵⁴ SUDs such as alcohol or opioid dependencies are highly comorbid with PTSD⁴⁵ and introduce a layer of complexity when managing painin these patients. Providers should be thoughtful when electing to treat acute or chronic pain with opioids and take particular care to establish realistic therapeutic goals if doing so. While patients with PTSD have a greater likelihood of having an SUD, undertreating pain risks exacerbating underlying PTSD symptoms.

Nonpharmacologic therapies, which include communicating, listening, and expressing compassion and understanding, should be utilized by inpatient providers as a first-line treatment in patients with PTSD who suffer from pain. Additionally, relaxation techniques, physical therapy, and physical activity⁵⁵ can be offered. Pharmacologically, nonopioid medications such as acetaminophen or NSAIDs should always be considered first. Should the use of opioids be deemed necessary, inpatient providers should preferentially use oral over intravenous medications and consider establishing a fixed timeframe for short-term opioids, which should be limited to a few days. Providers should communicate clear expectations with their patients to maximize the desired effect of any specific treatment while minimizing the risk of medication side effects with the goal of agreeing on a short yet effective treatment course.

Anxiety and Anger

One of the most challenging situations for the inpatient provider is encountering a patient who is anxious, angry, or hypervigilant. Mismatch between actual and expected communication between the provider and the patient can lead to frustration and anxiety. A trauma-informed care approach would suggest that frequent and thorough communication with patients may prevent or ameliorate the stresses and anxieties of hospitalization that may manifest as anger because of retraumatization. Hospitalizations usually lead to disruption of normal routine (eg, unpredictable meal times or medication administration), interrupted sleep (eg, woken up for blood draws or provider evaluation), and lack of control of schedule (eg, unsure of exact time when a procedure may be occurring), any of which may trigger symptoms of anxiety and anger in patients with PTSD and lead to hypervigilance.

If situations involving patient anxiety do arise, employ compassion and communication. Extra time spent with the patient, while challenging in the hectic hospital environment, is critical, and nonpharmacological treatments should be the priority. Engaging patients by asking about their PTSD triggers²⁴ may help prevent exacerbations. For example, some patients may specify how they prefer to be woken up to prevent startle reactions. PTSD triggers can be reduced via effective communication with the entire healthcare team. Some immediate yet effective strategies are listening, validation, and negotiation. Benzodiazepine or antipsychotic usage should be avoided.³⁶ Inpatient social work and comanagement with psychiatry involvement may be helpful in more severe exacerbations. A small observational study of patients hospitalized for severe PTSD found an association between walking more during hospitalization and fewer PTSD symptoms,⁵⁶ suggesting that staying active could be helpful for inpatients with PTSD who are able to safely ambulate.

PTSD is a common comorbidity among hospitalized patients in the United States. Typical hospital routines may exacerbate symptoms of PTSD such as anxiety and anger. Inpatient providers can play an important role in making hospitalizations go more smoothly for these patients by using principles consistent with trauma-informed care. Specifically, partnering with patients to construct a plan that preserves their sleep routines and accounts for potential triggers for decompensation can improve the hospital experience for patients with PTSD. Some PTSD interventions require additional investment from the healthcare system to deploy, such as staff training in trauma-­informed care and reflective listening techniques. Electronic health record–based protocols and order sets for patients with PTSD can leverage available resources. Further research should evaluate hospital outcomes that result from a more tailored approach to the care of patients with PTSD. More effective, patient-centered PTSD care could lower rates of leaving against medical advice and improve the inpatient experience for patients and providers alike.

Posttraumatic stress disorder (PTSD) is a syndrome that occurs after exposure to a significant traumatic event and is characterized by persistent, debilitating symptoms that fall into four “diagnostic clusters” as outlined in the Diagnostic and Statistical Manual of Mental Disorders-Version V (DSM-V). Patients may experience intrusive thoughts, avoidance of distressing stimuli, persistent negative mood, and hypervigilance, all of which last longer than 1 month.¹

A national survey of United States households conducted during 2001-2003 estimated the 12-month prevalence of PTSD among adults to be 3.5%.² Lifetime prevalence has been found to be between 6.8%³ and 7.8%.⁴ PTSD is more common in veterans. The prevalence of PTSD in veterans differs depending on the conflict in which the veteran participated. Vietnam veterans have an estimated lifetime prevalence of approximately 30%,^5,6 Gulf War veterans approximately 15%,⁷ and veterans of more recent conflicts in Afghanistan and Iraq of approximately 21%.⁸ With the MISSION Act moving more veteran care into the private sector, non-VA inpatient providers will need to become better versed in PTSD.⁹

Patients with PTSD have more contact with the healthcare system, even for non–mental health problems,^8,10-13 and a significantly higher burden of medical comorbities,¹⁴ such as diabetes mellitus, liver disease, gastritis and gastric ulcers, HIV, arthritis,¹⁵ and coronary heart disease.¹⁶ Veterans with PTSD are hospitalized three times more often than are those with no mental health diagnoses,⁸ and patients with psychiatric comorbidities have higher lengths of stay.¹⁷ More than 1.4 million hospitalizations occurring during 2002-2011 had either a primary or secondary associated diagnosis of PTSD, with total inflation-­adjusted charges of 34.9 billion dollars.¹⁸ In the inpatient sample from this study, greater than half were admitted for a primary diagnosis of mental diseases and disorders (Major Diagnostic Category [MDC] 19). Following mental illness, the most common primary diagnoses for men were MDC 5 (Circulatory System, 12.1%), MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 9.2%), and MDC 4 (Respiratory System, 7.4%), while the most common categories for women were MDC 20 (Alcohol/Drug Use or Induced Mental Disorder, 5.8%), MDC 21 (Injuries, Poison, and Toxic Effect of Drugs, 4.9%), and MDC 6 (Digestive System, 4.5%).¹⁸

In both the inpatient and outpatient settings, a fundamental challenge to comprehensive PTSD management is correctly diagnosing this condition.¹⁹ Confounding the difficulties in diagnosis are numerous comorbidities. In addition to the physical comorbidities described above, more than 70% of patients with PTSD have another psychological comorbidity such as affective disorders, anxiety disorders, or substance use disorder/dependency.²⁰

Given that PTSD may be an underrecognized burden on the healthcare system, we sought to better understand how PTSD could affect hospitalized patients admitted for medical problems by conducting this narrative review. Additionally, three of the authors collaborated with the VA Employee Education Service to conduct a needs assessment of VA hospitalists in 2013. Respondents identified managing and educating patients and families about PTSD as a major educational need (unpublished data available upon request from the corresponding author). Therefore, our aims were to present a synthesis of existing literature, familiarize readers with the tenets of trauma-­informed care as a framework to guide care for these patients, and generate ideas for changes that inpatient providers could implement now. We began by consulting a research librarian at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin, who searched the following databases: PsycInfo, CINAHL, MEDLINE, and PILOTS (a PTSD/trauma specific database). Search terms included hospital, hospitalized, and hospitalization, as well as traumatic stress, posttraumatic stress, and PTSD. Pertinent guidelines and the reference lists from included papers were examined. We focused on papers that described patients admitted for medical problems other than PTSD because those patients who are admitted for PTSD-­related problems should be primarily ma­naged by psychiatry (not hospitalists) with the primary focus of their hospitalization being their PTSD. We also excluded papers about patients developing PTSD secondary to hospitalization, which already has a well-developed literature.^21-23

The literature is sparse describing frequency or type of problems encountered by hospitalized medical patients with PTSD. A recent small survey study reported that 40% of patients anticipated triggers for their PTSD symptoms in the hospital; such triggers included loud noises and being shaken awake.²⁴ Two papers describe case vignettes of patients who had exacerbations of their PTSD while in the Intensive Care Unit (ICU), although neither contain frequency or severity data.^25,26 Approximately 8% of patients in VA ICUs have PTSD,²⁷ and a published abstract suggests that they appear to require more sedation than do patients without PTSD.²⁸ Another published case report describes a patient with recurrent PTSD symptoms (nightmares) after moving into a nursing home.²⁹ These papers suggest other providers have recognized and are concerned about hospitalized patients with PTSD. At present, there are no data to quantify how often hospitalized patients have PTSD exacerbations or how troublesome such exacerbations are to these patients.

Given that there is little empiric literature to guide inpatient management of PTSD as a comorbidity in hospitalized medical patients, we extrapolate some information from the outpatient setting. PTSD is often underdiagnosed and underreported by individual patients in the outpatient setting.³⁰ Failure to have an associated diagnosis of PTSD may lead to underrecognition and undertreatment of these patients by inpatient providers in the hospital setting. Additionally, the numerous psychological and physical comorbidities in PTSD can create unique challenges in properly managing any single problem in these patients.²⁰ Armed with this knowledge, providers should be vigilant in the recognition, assessment, and treatment of PTSD.

Trauma-Informed Care: A Conceptual Model

Trauma-informed care is a mindful and sensitive approach to caring for patients who have suffered trauma.³¹ It requires understanding that many people have suffered trauma in their lives and that the trauma continues to impact many aspects of their lives.³² Trauma-informed care has many advocates and has been implemented across myriad health and social services settings.³³ Its principles can be applied in both the inpatient and outpatient hospital settings. While it is an appropriate approach to patients with PTSD, it is not specific to PTSD. People who have suffered sexual trauma, intimate partner violence, child abuse, or other exposures would also be included in the group of people for whom trauma-informed care is a suitable approach. There are four key assumptions to a trauma-­informed approach to care (the 4 R’s): (1) realization that trauma affects an individual’s coping strategies, relationships, and health; (2) recognition of the signs of trauma; (3) having an appropriate, planned response to patients identified as having suffered a trauma; and (4) resisting retraumatization in the care setting.^31,32

General Approach to Treating Medical Patients With PTSD in the Inpatient Setting

Recognition

Consistent with a trauma-informed care approach, inpatient providers should be able to recognize patients who may have PTSD. First, careful review of the past medical history may show some patients already carry this diagnosis. Second, patients with PTSD often have other comorbidities that could offer a clue that PTSD could be present as well; for example, risk for PTSD is increased when mood, anxiety, or substance use disorders are present.²⁰ When PTSD is suspected, screening is a reasonable next step.

The Primary Care-PTSD-5 (PC-PTSD-5) is a validated screening tool used in the outpatient setting.³⁴ It is easily administered and has good predictive validity (positive likelihood ratio [LR+] of 6.33 and LR– of 0.06). It begins with a question of whether the patient has ever experienced a trauma. A positive initial response triggers a series of five yes/no questions. Answering “yes” to three or more questions is a positive screen. A positive screen should result in consultation to psychiatry to conduct more formal evaluation and guide longer-term management.

Collaboration

Individual trauma-focused psychotherapy is the primary treatment of choice for PTSD with strong evidence supporting its practice.³⁵ This treatment is administered by a psychiatrist or psychologist and will be limited in the inpatient medical setting. Current recommendations suggest pharmacotherapy only when individualized trauma-focused psychotherapy is not available, the patient declines it, or as an adjunct when psychotherapy alone is not effective.³⁶ Therefore, inpatient providers may see patients who are prescribed selective serotonin reuptake inhibitors (eg, paroxetine, fluoxetine) or serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine).³⁶ In the past, PTSD-related nightmares were often treated with prazosin.³⁷ However, a recent randomized controlled trial of prazosin in veterans with PTSD failed to show significant improvement in nightmares.³⁸ Hence, current guidelines do not recommend prazosin as a first-line therapy.³⁹ For hospitalized patients with PTSD symptoms refractory to the interventions outlined herein, particularly those patients with possible borderline personality traits (as suggested by severe anger and impulsivity), we strongly recommend partnering with psychiatry. Finally, given the high prevalence of substance use disorders (SUDs) in PTSD patients, awareness and treatment of comorbidities such as opioid and alcohol dependence must be concurrently addressed.

Individualizing Care

It is essential for the healthcare team to identify ways to meet each patient’s immediate needs. Many of the ideas proposed below are not specific to PTSD; many require an interprofessional approach to care.⁴⁰ From a trauma-informed care standpoint, this is akin to having a planned response for patients who have suffered trauma. Assessing the individual’s needs and incorporating therapeutic modalities such as reflective listening, broadening safe opportunities for control, and providing complementary and integrative medicine (IM) therapies may help manage symptoms and establish rapport.⁴¹ Through reflective listening, a collaborative approach can be established to identify background, triggers, and a safe approach for managing PTSD and its comorbid conditions. Ensuring frequent communication and allowing the patient to be at the center of decision-making establishes a safe environment and promotes positive rapport between the patient and healthcare team.³⁶ Providing a sense of control by involving the patients in their healthcare decisions and in the structure of care delivery may benefit the patients’ well-being. Furthermore, incorporating IM encourages rest and relaxation in the chaotic hospital environment. Suggested IM interventions include deep breathing, aromatherapy, guided imagery, muscle relaxation, and music therapy.^42,43

Key Inpatient Issues Affecting PTSD

In the following sections, we outline common clinical situations that may exacerbate PTSD symptoms and propose some evidence-based responses (Table). In general, nonpharmacologic approaches are favored over pharmacologic approaches for patients with PTSD.

Sleep Hygiene

Sleep problems are very common in patients with PTSD, with nightmares occurring in more than 70% of patients and insomnia in 80%.⁴⁴ In PTSD, sleep problems are linked to poor physical health and other health outcomes^45,46 and may exacerbate other PTSD symptoms.⁴

Treating the sleep problems that occur with PTSD is an important aspect of PTSD care. Usually administered in the outpatient setting, the treatment of choice is cognitive-behavioral therapy (CBT).⁴⁸ Sleep-specific CBT focuses, among other things, on strategies that encourage good sleep hygiene,⁴⁹ which includes promoting regular sleep/wake-up times and specific bedtime routines, avoiding stimulation (eg, light, noise, TV) or excessive liquids before bed, refraining from daytime naps, and using relaxation techniques. Many of these recommendations seem at odds with hospital routines, which may contribute to decompensation of hospitalized patients with PTSD.

While starting sleep-specific CBT in the hospital may not be realistic, we suggest the following goals and strategies as a starting place for promoting healthy sleep for hospitalized patients with PTSD. To begin, factors affecting sleep hygiene should be addressed. Inpatient providers could pay more attention to intravenous (IV) fluid orders, perhaps adjusting them to run only during the daytime hours. Medications can be scheduled at times conducive to maintaining home routines. Avoiding the administration of diuretics close to bedtime may decrease the likelihood of frequent nighttime wakening. Grouping patient care activities, such as bathing or wound care, during daytime hours may allow more opportunities for rest at night. Incorporating uninterrupted sleep protocols, such as quiet hours between 10pm and 6am, may enhance sleep quality in the appropriately selected patient.⁵⁰ Although pharmacological interventions to improve sleep in the hospital may be initially beneficial, nonpharmacological interventions as described above should be incorporated for long-term maintenance of enhanced sleep quality.

Second, providers need to ask about established home bedtime routines and facilitate implementation in the hospital. Through collaboration with patients, providers can incorporate an individualized plan of care for sleep early in hospitalization.⁵⁰ Partnering with nurses is also essential to creating a sleep-friendly environment that can improve patient experiences.⁵¹ Breathing exercises, meditating, listening to music and praying are all examples of “bedtime wind down” strategies recommended in sleep-specific CBT.⁴⁹ Many of these could be successfully implemented in the hospital and may benefit other hospitalized patients too.⁵² In patients with PTSD and obstructive sleep apnea, continuous positive airway pressure (CPAP) reduces nightmares, and if inpatients are on CPAP at home, it should be continued in the hospital.⁵³

Pain

If sleep disturbance is the hallmark of PTSD,⁴⁷ chronic pain is its coconspirator.¹⁵ Uncontrolled pain can make it much more difficult to treat patients with PTSD, which in turn may lead to further decompensation from a mental health standpoint.⁵⁴ SUDs such as alcohol or opioid dependencies are highly comorbid with PTSD⁴⁵ and introduce a layer of complexity when managing painin these patients. Providers should be thoughtful when electing to treat acute or chronic pain with opioids and take particular care to establish realistic therapeutic goals if doing so. While patients with PTSD have a greater likelihood of having an SUD, undertreating pain risks exacerbating underlying PTSD symptoms.

Nonpharmacologic therapies, which include communicating, listening, and expressing compassion and understanding, should be utilized by inpatient providers as a first-line treatment in patients with PTSD who suffer from pain. Additionally, relaxation techniques, physical therapy, and physical activity⁵⁵ can be offered. Pharmacologically, nonopioid medications such as acetaminophen or NSAIDs should always be considered first. Should the use of opioids be deemed necessary, inpatient providers should preferentially use oral over intravenous medications and consider establishing a fixed timeframe for short-term opioids, which should be limited to a few days. Providers should communicate clear expectations with their patients to maximize the desired effect of any specific treatment while minimizing the risk of medication side effects with the goal of agreeing on a short yet effective treatment course.

Anxiety and Anger

One of the most challenging situations for the inpatient provider is encountering a patient who is anxious, angry, or hypervigilant. Mismatch between actual and expected communication between the provider and the patient can lead to frustration and anxiety. A trauma-informed care approach would suggest that frequent and thorough communication with patients may prevent or ameliorate the stresses and anxieties of hospitalization that may manifest as anger because of retraumatization. Hospitalizations usually lead to disruption of normal routine (eg, unpredictable meal times or medication administration), interrupted sleep (eg, woken up for blood draws or provider evaluation), and lack of control of schedule (eg, unsure of exact time when a procedure may be occurring), any of which may trigger symptoms of anxiety and anger in patients with PTSD and lead to hypervigilance.

If situations involving patient anxiety do arise, employ compassion and communication. Extra time spent with the patient, while challenging in the hectic hospital environment, is critical, and nonpharmacological treatments should be the priority. Engaging patients by asking about their PTSD triggers²⁴ may help prevent exacerbations. For example, some patients may specify how they prefer to be woken up to prevent startle reactions. PTSD triggers can be reduced via effective communication with the entire healthcare team. Some immediate yet effective strategies are listening, validation, and negotiation. Benzodiazepine or antipsychotic usage should be avoided.³⁶ Inpatient social work and comanagement with psychiatry involvement may be helpful in more severe exacerbations. A small observational study of patients hospitalized for severe PTSD found an association between walking more during hospitalization and fewer PTSD symptoms,⁵⁶ suggesting that staying active could be helpful for inpatients with PTSD who are able to safely ambulate.

PTSD is a common comorbidity among hospitalized patients in the United States. Typical hospital routines may exacerbate symptoms of PTSD such as anxiety and anger. Inpatient providers can play an important role in making hospitalizations go more smoothly for these patients by using principles consistent with trauma-informed care. Specifically, partnering with patients to construct a plan that preserves their sleep routines and accounts for potential triggers for decompensation can improve the hospital experience for patients with PTSD. Some PTSD interventions require additional investment from the healthcare system to deploy, such as staff training in trauma-­informed care and reflective listening techniques. Electronic health record–based protocols and order sets for patients with PTSD can leverage available resources. Further research should evaluate hospital outcomes that result from a more tailored approach to the care of patients with PTSD. More effective, patient-centered PTSD care could lower rates of leaving against medical advice and improve the inpatient experience for patients and providers alike.

A previously healthy 4-year-old boy presented to his pediatrician for nasal congestion, left ear pain, and intermittent fevers, which he’d been experiencing for 2 days. His exam was consistent with acute otitis media. Cefdinir was prescribed given a rash allergy to amoxicillin. His fever, congestion, and otalgia improved the next day.

Three days later he developed abdominal pain, fever, and labored breathing; his mother brought him to the emergency department (ED). His temperature was 38.0 °C, heart rate 141 beats per minute, blood pressure 117/71 mm Hg, respiratory rate 22 breaths per minute; he had oxygen saturation of 96% on ambient air. Despite mild accessory muscle use, he appeared comfortable and interactive. His left tympanic membrane was bulging without erythema. His neck was supple and mucous membranes moist. He had neither cervical lymphadenopathy nor conjunctival pallor. The cardiopulmonary exam was normal except for tachycardia. His abdomen was soft and not distended without organomegaly or tenderness.

Upper respiratory tract symptoms are commonly encountered in pediatrics and most often result from self-limited viral processes. Evaluation of a child with upper respiratory tract symptoms aims to identify serious causes like meningitis, as well as assessing the need for antimicrobial therapy. Supportive management is often appropriate in otitis media. His new, more concerning symptoms portend either a progression of the original process causing his upper respiratory tract symptoms or a separate etiology. It is key to determine which signs and symptoms are associated with the primary process and which are compensatory or secondary. If he were to be more ill appearing, for example, it is possible that his respiratory distress may be related to an underlying systemic illness rather than a primary lung process. Respiratory distress, abdominal pain, and fever could be a result of sepsis from an intrabdominal process such as ruptured appendicitis, intussusception, or malrotation with volvulus. Other causes of sepsis, such as meningitis or severe mastoiditis, both rare complications of otitis media, should be considered, although he does not appear severely ill. Acute myelogenous leukemia or other malignancies and illnesses associated with immunodeficiency can present with sepsis and chloromas in the middle ear that can be misconstrued as otitis media.

A chest radiograph demonstrated left lower lobe patchy opacities concerning for pneumonia. Rapid respiratory syncytial virus and influenza antigen test results were negative. Laboratory testing for general bloodwork was not obtained. He was administered a single dose of intramuscular ceftriaxone, prescribed a 5-day course of azithromycin, and discharged home. The child’s breathing gradually improved, but he continued to have subjective fevers. Two days later, he developed dark red urine. His mother brought him back to the outpatient clinic.

At the time of the ED visit, a diagnosis of community-acquired pneumonia was plausible given fever, mildly increased work of breathing, and an opacification on chest radiography. Most community-acquired pneumonia is caused by viruses; common bacterial causes for his age include Streptococcus pneumoniae and Moraxella catarrhalis. The first-line treatment for uncomplicated community-acquired pneumonia in children is amoxicillin, but this was appropriately avoided given his allergy.

The persistent fevers are surprising. The improvement in breathing corresponds to the treatment (and resolution) of community-acquired pneumonia. However, the development of dark urine does not. Red urine—in the absence of ingested pigments (such as those found in beets)—usually results from hematuria, hemoglobinuria, or myoglobinuria. Gross hematuria can originate from the kidneys to the urethral meatus. Abdominal masses, kidney trauma, or underlying kidney disease may all present with gross hematuria (or microscopic hematuria, seen only on urinalysis). The urine should be examined for the presence of heme, protein, and for evidence of infection; microscopy should be performed to examine for cellular casts and dysmorphic red cells. Tests of renal function, a comprehensive metabolic panel, evaluation of hematologic indexes, and assessments of inflammatory markers should be performed.

The child lived with his parents and had no siblings. He experienced no physical trauma, and there was no family history of kidney disease or hematuria. His father had a persistent cough and fever for 1 month, but recovered around the time the patient began to experience his initial symptoms. This was the patient’s third diagnosis of pneumonia. He had not traveled and was up to date with immunizations. He attended day care.

The fact that this is not the first episode of “pneumonia” raises important possibilities. The most likely one is that the child has had multiple viral infections; however, he could have an underlying primary immunodeficiency (PI) that predisposes him to recurrent infections. More severe PIs often present with recurrent sepsis, bacteremia, and failure to thrive, none of which were present in this case. Less severe PIs (such as selective IgA deficiency) could be possible. Another possibility is that these recurrent episodes of pneumonia are a relapsing and remitting noninfectious process, such as an antineutrophil cytoplasmic antibodies–associated vasculitis or anti–glomerular basement membrane disease. The patient’s father’s recent prolonged respiratory symptoms may be suggestive of pertussis or a “walking pneumonia” potentially caused by Mycoplasma or another atypical bacterium.

His temperature was 36.9 °C, heart rate 107 beats per minute, blood pressure was 106/67 mm Hg, and respiratory rate was 24 breaths per minute with oxygen saturation of 100% on ambient air. He was well appearing. His mucous membranes were moist, and oropharynx was clear. He had scleral icterus. The cardiopulmonary exam was normal. He had no significant lymphadenopathy, hepatosplenomegaly, or rashes.

The finding of jaundice is an important diagnostic pivot point, especially when combined with hematuria. The next step is determining if the jaundice is resulting from unconjugated or conjugated hyperbilirubinemia; the former most often stems from hemolysis or impairment in conjugation, while the latter results from intrahepatic or extrahepatic biliary defects. Tests for hepatobiliary injury including evaluations of alanine and aspartate aminotransferases and alkaline phosphatase, as well as for hepatic function such as tests of coagulation, should be performed.

The patient was referred to the ED and admitted for further evaluation. A complete blood count revealed a white blood cell (WBC) count of 10,700/µL (61% polymorphonuclear neutrophils, 30% lymphocytes, 5% monocytes, 3% eosinophils, 1% basophils), hemoglobin count was 10.3 g/dL (reticulocyte 2% with absolute reticulocyte count 58,400/μL), and platelet count was 265,000/µL. Components of the basic metabolic panel were within reference ranges except for a mildly elevated blood urea nitrogen level of 14 mg/dL with normal creatinine level of 0.3 mg/dL. Total protein was 6.7 g/dL (reference range, 6.4-8.3) and albumin 3.9 g/dL (reference range, 3.4-4.8). Alkaline phosphatase level was 188 U/L (reference range, 44-147), aspartate aminotransferase level 76 U/L (reference range, 0-40), and alanine aminotransferase level 12 U/L (reference range, 7-40). Total bilirubin level was 2.4 mg/dL (reference range, less than 1.5) with direct bilirubin level of 0.4 mg/dL. His C-reactive protein level was 1.5 mg/mL (reference range, 0-0.75). Creatinine kinase (CK) level was 2,550 U/L (reference range, 2-198). International Normalized Ratio (INR) was 1.0. Urinalysis was notable for 2+ proteinuria, large hemoglobin pigment, and 6 red blood cells per high power field (reference range, 0-4).

His blood urea nitrogen is elevated, reflecting either prerenal azotemia or increased absorption of nitrogenous products. Unconjugated hyperbilirubinemia may result from impaired hepatic bilirubin uptake (such as in heart failure or portosystemic shunts), impaired bilirubin conjugation (resulting from genetic conditions or drugs), or excess bilirubin production (such as in hemolysis); his anemia and lack of other evidence of hepatic dysfunction point to hemolysis as the etiology. The reticulocyte production index is approximately 1%, which suggests that an increase in erythrocyte generation is present but inadequate. This, however, does not mean that an erythrocyte production abnormality is present since reticulocytosis can be delayed in many cases of acute hemolytic anemia. It is also possible that the same hemolytic process is affecting mature and immature erythrocytes. A peripheral blood smear should be reviewed for evidence of intravascular hemolysis and testing for autoimmune hemolysis should be performed. Notably, his white blood cell and platelet counts are preserved, which makes a bone marrow–involved malignancy or infiltrative process less likely. The alkaline phosphatase elevation may result from either intrahepatic or extrahepatic biliopathy; bone damage is also possible. The elevation of aspartate aminotransferase, CK, and potassium, along with marked urinary heme pigment, may indicate muscle damage; the most common myositis in children is benign acute childhood myositis resulting from viral infection. However, the moderate level of CK elevation seen in this case is nonspecific and can result from many different etiologies. A metabolic myopathy, such as carnitine palmitoyltransferase II deficiency, can be made worse by metabolic stress and result in rhabdomyolysis; the presentations of inborn errors of metabolism are varied and a planned-out, stepwise approach in evaluation is fundamental.

Lactic acid dehydrogenase (LDH) level was 1,457 U/L (reference range, 140-280), and haptoglobin level was less than 6 mg/dL (reference range, 30-200). Peripheral blood smear demonstrated occasional atypical, reactive-appearing lymphocytes with red cell clumping and agglutination, as well as rare target, burr, and fragmented red cells. Test results for urine myoglobin were negative. Results of urine culture were negative. No blood culture was collected.

The elevated LDH, decreased haptoglobin, and findings on the peripheral blood smear confirm hemolysis. The clumping of erythrocytes can be artifactual in the preparation of peripheral smears, but when considered in the context of hemolysis, may be clinically important. Clumping of erythrocytes on the peripheral smear indicates the binding of a protein to antigens on the erythrocyte membrane; when this occurs below body temperature, this is consistent with the presence of a “cold agglutinin,” usually an IgM antibody directed at erythrocyte surface antigens that causes agglutination and destruction, especially in cooler areas of the body. This is a well-known complication of Mycoplasma pneumoniae infections as well as Epstein-Barr virus (EBV) infections; it may also occur with lymphoid malignancies or autoimmune disease.

Direct Coombs IgG test findings were negative, direct Coombs C3 test was positive, and direct Coombs polyspecific test was positive. M pneumoniae IgG antibody level was 1.4 mg/dL (reference ranges: <0.9, negative; 0.91-1.09, equivocal; >1.1, positive); M pneumoniae IgM level was 529 U/mL (reference range: <770, negative). EBV capsid IgM and IgG levels were undetectable. EBV nuclear antigen IgG level was also undetectable. EBV viral load was fewer than 10 copies/mL. Antinuclear antibodies (ANA) level was negative. General IgE and IgM levels were normal, at 11 and 81 mg/dL, respectively. Repeat complete blood count showed WBC of 7,800/µL, hemoglobin of 8.7 g/dL, and platelet count of 341,000/µL. The patient’s hemoglobin remained stable during hospitalization.

This directed testing is helpful in further classifying the patient’s hemolytic anemia. Autoimmune hemolytic anemias are classified into warm antibody–mediated, cold antibody–mediated, and mixed-type forms; drug-induced and alloimmune hemolytic anemias also occur. In addition, both systemic lupus erythematosus and antiphospholipid antibody syndrome can have hemolytic anemia with variable Coombs testing results; neither fit well in this case. The absence of red blood cell–directed IgG antibodies substantially decreases the likelihood of warm antibody–mediated hemolytic anemia. In cold antibody–mediated hemolytic anemia, antibodies bind to the erythrocyte membrane and then adhere to complement C3, which leads to both intravascular and extravascular hemolysis. Important types of cold antibody–mediated hemolytic anemia in children are primary and secondary cold agglutinin disease, along with paroxysmal cold hemoglobinuria. The Donath-Landsteiner test can be helpful in differentiating these conditions. Antibodies to Mycoplasma may be delayed in response to acute infection, and a child who is reinfected may only produce IgG antibodies. Given the patient’s clinical stability and previous health, the most likely diagnosis is Mycoplasma-induced cold antibody–mediated hemolytic anemia. It may be helpful to check convalescent titers to Mycoplasma in 2 to 4 weeks.

Donath-Landsteiner (D-L) antibody test results were positive. Medication-derived hemolytic anemia testing was conducted, but the presence of positive D-L antibody makes the test results inconclusive. This ultimately led to a diagnosis of paroxysmal cold hemoglobinuria (PCH), presumably triggered by a viral syndrome. Convalescent titers to Mycoplasma were not checked given clinical improvement. Because the patient’s hemoglobin was stable during hospitalization, he was not treated with steroids. His parents were counseled on avoiding cold temperatures for several days. Within 1 month, his hemoglobin had recovered without further evidence of hemolysis.

Hemolytic anemia refers to the accelerated destruction of red blood cells and can be further classified as acquired or hereditary.¹ Hereditary conditions causing hemolytic anemia include enzymopathies (eg, glucose-6-phosphate dehydrogenase deficiency), hemoglobinopathies (eg, sickle cell disease), and membrane abnormalities (eg, hereditary spherocytosis). Acquired pathologies include microangiopathic hemolytic anemia (MAHA), anemias directly caused by certain infections such as malaria, and immune-mediated (Coombs-positive) hemolytic anemias.

MAHA can sometimes be life-threatening and is therefore important to identify quickly. In the right clinical context, such processes may be rapidly recognized by the presence of schistocytes on blood smear in addition to an elevated serum LDH level. Schistocytes suggest mechanical destruction of erythrocytes in the vasculature, the hallmark of MAHA. Important MAHAs include thrombocytopenic purpura, hemolytic-uremic syndrome, and disseminated intravascular coagulation. Though this patient did have a mildly elevated LDH, MAHA was less likely because there were no schistocytes on the blood smear.

Autoimmune hemolytic anemias (AIHAs) are another important subset of acquired hemolytic anemias. AIHAs occur when there is antibody-mediated destruction of erythrocytes. The direct Coombs test evaluates for antibody- or complement-­coated erythrocytes. After administration of anti-IgG and anti-­C3 serum, the test evaluates for agglutination of the red cells caused by attached antibodies or complement. Coombs-­positive AIHA can also be categorized by the temperature of agglutination. “Warm” hemolysis often involves IgG autoantibodies (ie, warm agglutinins), while “cold” antibodies, usually IgM autoantibodies, bind at colder temperatures (0-4 °C) and activate complements, including C3. In this patient, the Coombs C3 was positive while the Coombs IgG was negative, which is more suggestive of a cold complement–mediated pathway.

Cold AIHA can be further categorized into primary cold agglutinin disease, secondary cold agglutinin disease, and PCH. Primary cold agglutinin disease is an autoimmune disorder that mostly occurs in adults. Secondary cold AIHA can often be triggered by bacterial infection (commonly M pneumoniae) or viruses including EBV, measles, and mumps.² Medications, including penicillin and cephalosporins, can also be implicated. Secondary cold AIHA is also linked with autoimmune diseases, such as systemic lupus erythematosus and lymphoproliferative disorders. PCH can be identified with the unique presence of a specific autoantibody (ie, D-L autoantibody) that agglutinates at cold temperatures but dissociates on subsequent rewarming.³ Complement remains affixed and activates hemolysis.

The D-L antibody responsible for PCH is an IgG antibody to the P-antigen present on the erythrocyte surface. Since the Coombs test is conducted at normal temperature, it will be positive for the affixed complement but not for IgG. The underlying mechanism for PCH was proposed by Julius Donath, MD, and Karl Landsteiner, MD, in 1904 and is considered to be the first description of autoimmune disease being precipitated by antibodies.⁴ The D-L antibody test itself is uncommonly performed and somewhat difficult to interpret, particularly in adults, and may lead to false-negative results.⁵

PCH is an acquired, cold AIHA more common to children^6,7 and may account for up to 33% of pediatric AIHA cases.⁸ Typical presentation is after an upper respiratory tract illness; however, the trigger is often not identified. Implicated triggers include a number of viruses.⁹ Clinical presentation includes findings of intravascular hemolysis similar to those in our patient. The pathogenic IgG autoantibody is polyclonal and is likely formed because of immune stimulation, which is consistent with the predominance of nonmalignant triggers of this disease process.¹⁰ Hemolysis and associated symptoms are often exacerbated with cold exposure; both typically resolve within 2 weeks. In recurrent cases, which are a minority, immunosuppression may be considered.¹⁰

PCH remains an often-understated cause of hemolytic anemia particularly in children. Lacking obvious pathognomonic clinical symptoms, it may be overlooked for other forms of AIHA or MAHA. However, with a structured approach to evaluation, as with this patient who had hematuria and jaundice, early diagnosis can prevent an unnecessarily extensive workup and can provide reassurance to patient and parents. By understanding the basic categories of hemolytic anemia, the relevant blood testing available, and interpretation of Coombs test results, clinicians can ensure that PCH is a diagnosis that is not left out in the cold.

• Examination for schistocytes on a blood smear can help identify life-threatening causes of hemolytic anemia.
• Characterization of cold AIHA includes defining the underlying etiology as primary cold agglutinin disease, secondary cold agglutinin disease, or PCH.
• PCH is a cold AIHA that is an underrecognized cause of hemolytic anemia in children. The diagnosis of PCH is made by testing for the presence of the D-L antibody.

A previously healthy 4-year-old boy presented to his pediatrician for nasal congestion, left ear pain, and intermittent fevers, which he’d been experiencing for 2 days. His exam was consistent with acute otitis media. Cefdinir was prescribed given a rash allergy to amoxicillin. His fever, congestion, and otalgia improved the next day.

Three days later he developed abdominal pain, fever, and labored breathing; his mother brought him to the emergency department (ED). His temperature was 38.0 °C, heart rate 141 beats per minute, blood pressure 117/71 mm Hg, respiratory rate 22 breaths per minute; he had oxygen saturation of 96% on ambient air. Despite mild accessory muscle use, he appeared comfortable and interactive. His left tympanic membrane was bulging without erythema. His neck was supple and mucous membranes moist. He had neither cervical lymphadenopathy nor conjunctival pallor. The cardiopulmonary exam was normal except for tachycardia. His abdomen was soft and not distended without organomegaly or tenderness.

Upper respiratory tract symptoms are commonly encountered in pediatrics and most often result from self-limited viral processes. Evaluation of a child with upper respiratory tract symptoms aims to identify serious causes like meningitis, as well as assessing the need for antimicrobial therapy. Supportive management is often appropriate in otitis media. His new, more concerning symptoms portend either a progression of the original process causing his upper respiratory tract symptoms or a separate etiology. It is key to determine which signs and symptoms are associated with the primary process and which are compensatory or secondary. If he were to be more ill appearing, for example, it is possible that his respiratory distress may be related to an underlying systemic illness rather than a primary lung process. Respiratory distress, abdominal pain, and fever could be a result of sepsis from an intrabdominal process such as ruptured appendicitis, intussusception, or malrotation with volvulus. Other causes of sepsis, such as meningitis or severe mastoiditis, both rare complications of otitis media, should be considered, although he does not appear severely ill. Acute myelogenous leukemia or other malignancies and illnesses associated with immunodeficiency can present with sepsis and chloromas in the middle ear that can be misconstrued as otitis media.

A chest radiograph demonstrated left lower lobe patchy opacities concerning for pneumonia. Rapid respiratory syncytial virus and influenza antigen test results were negative. Laboratory testing for general bloodwork was not obtained. He was administered a single dose of intramuscular ceftriaxone, prescribed a 5-day course of azithromycin, and discharged home. The child’s breathing gradually improved, but he continued to have subjective fevers. Two days later, he developed dark red urine. His mother brought him back to the outpatient clinic.

At the time of the ED visit, a diagnosis of community-acquired pneumonia was plausible given fever, mildly increased work of breathing, and an opacification on chest radiography. Most community-acquired pneumonia is caused by viruses; common bacterial causes for his age include Streptococcus pneumoniae and Moraxella catarrhalis. The first-line treatment for uncomplicated community-acquired pneumonia in children is amoxicillin, but this was appropriately avoided given his allergy.

The persistent fevers are surprising. The improvement in breathing corresponds to the treatment (and resolution) of community-acquired pneumonia. However, the development of dark urine does not. Red urine—in the absence of ingested pigments (such as those found in beets)—usually results from hematuria, hemoglobinuria, or myoglobinuria. Gross hematuria can originate from the kidneys to the urethral meatus. Abdominal masses, kidney trauma, or underlying kidney disease may all present with gross hematuria (or microscopic hematuria, seen only on urinalysis). The urine should be examined for the presence of heme, protein, and for evidence of infection; microscopy should be performed to examine for cellular casts and dysmorphic red cells. Tests of renal function, a comprehensive metabolic panel, evaluation of hematologic indexes, and assessments of inflammatory markers should be performed.

The child lived with his parents and had no siblings. He experienced no physical trauma, and there was no family history of kidney disease or hematuria. His father had a persistent cough and fever for 1 month, but recovered around the time the patient began to experience his initial symptoms. This was the patient’s third diagnosis of pneumonia. He had not traveled and was up to date with immunizations. He attended day care.

The fact that this is not the first episode of “pneumonia” raises important possibilities. The most likely one is that the child has had multiple viral infections; however, he could have an underlying primary immunodeficiency (PI) that predisposes him to recurrent infections. More severe PIs often present with recurrent sepsis, bacteremia, and failure to thrive, none of which were present in this case. Less severe PIs (such as selective IgA deficiency) could be possible. Another possibility is that these recurrent episodes of pneumonia are a relapsing and remitting noninfectious process, such as an antineutrophil cytoplasmic antibodies–associated vasculitis or anti–glomerular basement membrane disease. The patient’s father’s recent prolonged respiratory symptoms may be suggestive of pertussis or a “walking pneumonia” potentially caused by Mycoplasma or another atypical bacterium.

His temperature was 36.9 °C, heart rate 107 beats per minute, blood pressure was 106/67 mm Hg, and respiratory rate was 24 breaths per minute with oxygen saturation of 100% on ambient air. He was well appearing. His mucous membranes were moist, and oropharynx was clear. He had scleral icterus. The cardiopulmonary exam was normal. He had no significant lymphadenopathy, hepatosplenomegaly, or rashes.

The finding of jaundice is an important diagnostic pivot point, especially when combined with hematuria. The next step is determining if the jaundice is resulting from unconjugated or conjugated hyperbilirubinemia; the former most often stems from hemolysis or impairment in conjugation, while the latter results from intrahepatic or extrahepatic biliary defects. Tests for hepatobiliary injury including evaluations of alanine and aspartate aminotransferases and alkaline phosphatase, as well as for hepatic function such as tests of coagulation, should be performed.

The patient was referred to the ED and admitted for further evaluation. A complete blood count revealed a white blood cell (WBC) count of 10,700/µL (61% polymorphonuclear neutrophils, 30% lymphocytes, 5% monocytes, 3% eosinophils, 1% basophils), hemoglobin count was 10.3 g/dL (reticulocyte 2% with absolute reticulocyte count 58,400/μL), and platelet count was 265,000/µL. Components of the basic metabolic panel were within reference ranges except for a mildly elevated blood urea nitrogen level of 14 mg/dL with normal creatinine level of 0.3 mg/dL. Total protein was 6.7 g/dL (reference range, 6.4-8.3) and albumin 3.9 g/dL (reference range, 3.4-4.8). Alkaline phosphatase level was 188 U/L (reference range, 44-147), aspartate aminotransferase level 76 U/L (reference range, 0-40), and alanine aminotransferase level 12 U/L (reference range, 7-40). Total bilirubin level was 2.4 mg/dL (reference range, less than 1.5) with direct bilirubin level of 0.4 mg/dL. His C-reactive protein level was 1.5 mg/mL (reference range, 0-0.75). Creatinine kinase (CK) level was 2,550 U/L (reference range, 2-198). International Normalized Ratio (INR) was 1.0. Urinalysis was notable for 2+ proteinuria, large hemoglobin pigment, and 6 red blood cells per high power field (reference range, 0-4).

His blood urea nitrogen is elevated, reflecting either prerenal azotemia or increased absorption of nitrogenous products. Unconjugated hyperbilirubinemia may result from impaired hepatic bilirubin uptake (such as in heart failure or portosystemic shunts), impaired bilirubin conjugation (resulting from genetic conditions or drugs), or excess bilirubin production (such as in hemolysis); his anemia and lack of other evidence of hepatic dysfunction point to hemolysis as the etiology. The reticulocyte production index is approximately 1%, which suggests that an increase in erythrocyte generation is present but inadequate. This, however, does not mean that an erythrocyte production abnormality is present since reticulocytosis can be delayed in many cases of acute hemolytic anemia. It is also possible that the same hemolytic process is affecting mature and immature erythrocytes. A peripheral blood smear should be reviewed for evidence of intravascular hemolysis and testing for autoimmune hemolysis should be performed. Notably, his white blood cell and platelet counts are preserved, which makes a bone marrow–involved malignancy or infiltrative process less likely. The alkaline phosphatase elevation may result from either intrahepatic or extrahepatic biliopathy; bone damage is also possible. The elevation of aspartate aminotransferase, CK, and potassium, along with marked urinary heme pigment, may indicate muscle damage; the most common myositis in children is benign acute childhood myositis resulting from viral infection. However, the moderate level of CK elevation seen in this case is nonspecific and can result from many different etiologies. A metabolic myopathy, such as carnitine palmitoyltransferase II deficiency, can be made worse by metabolic stress and result in rhabdomyolysis; the presentations of inborn errors of metabolism are varied and a planned-out, stepwise approach in evaluation is fundamental.

Lactic acid dehydrogenase (LDH) level was 1,457 U/L (reference range, 140-280), and haptoglobin level was less than 6 mg/dL (reference range, 30-200). Peripheral blood smear demonstrated occasional atypical, reactive-appearing lymphocytes with red cell clumping and agglutination, as well as rare target, burr, and fragmented red cells. Test results for urine myoglobin were negative. Results of urine culture were negative. No blood culture was collected.

The elevated LDH, decreased haptoglobin, and findings on the peripheral blood smear confirm hemolysis. The clumping of erythrocytes can be artifactual in the preparation of peripheral smears, but when considered in the context of hemolysis, may be clinically important. Clumping of erythrocytes on the peripheral smear indicates the binding of a protein to antigens on the erythrocyte membrane; when this occurs below body temperature, this is consistent with the presence of a “cold agglutinin,” usually an IgM antibody directed at erythrocyte surface antigens that causes agglutination and destruction, especially in cooler areas of the body. This is a well-known complication of Mycoplasma pneumoniae infections as well as Epstein-Barr virus (EBV) infections; it may also occur with lymphoid malignancies or autoimmune disease.

Direct Coombs IgG test findings were negative, direct Coombs C3 test was positive, and direct Coombs polyspecific test was positive. M pneumoniae IgG antibody level was 1.4 mg/dL (reference ranges: <0.9, negative; 0.91-1.09, equivocal; >1.1, positive); M pneumoniae IgM level was 529 U/mL (reference range: <770, negative). EBV capsid IgM and IgG levels were undetectable. EBV nuclear antigen IgG level was also undetectable. EBV viral load was fewer than 10 copies/mL. Antinuclear antibodies (ANA) level was negative. General IgE and IgM levels were normal, at 11 and 81 mg/dL, respectively. Repeat complete blood count showed WBC of 7,800/µL, hemoglobin of 8.7 g/dL, and platelet count of 341,000/µL. The patient’s hemoglobin remained stable during hospitalization.

This directed testing is helpful in further classifying the patient’s hemolytic anemia. Autoimmune hemolytic anemias are classified into warm antibody–mediated, cold antibody–mediated, and mixed-type forms; drug-induced and alloimmune hemolytic anemias also occur. In addition, both systemic lupus erythematosus and antiphospholipid antibody syndrome can have hemolytic anemia with variable Coombs testing results; neither fit well in this case. The absence of red blood cell–directed IgG antibodies substantially decreases the likelihood of warm antibody–mediated hemolytic anemia. In cold antibody–mediated hemolytic anemia, antibodies bind to the erythrocyte membrane and then adhere to complement C3, which leads to both intravascular and extravascular hemolysis. Important types of cold antibody–mediated hemolytic anemia in children are primary and secondary cold agglutinin disease, along with paroxysmal cold hemoglobinuria. The Donath-Landsteiner test can be helpful in differentiating these conditions. Antibodies to Mycoplasma may be delayed in response to acute infection, and a child who is reinfected may only produce IgG antibodies. Given the patient’s clinical stability and previous health, the most likely diagnosis is Mycoplasma-induced cold antibody–mediated hemolytic anemia. It may be helpful to check convalescent titers to Mycoplasma in 2 to 4 weeks.

Donath-Landsteiner (D-L) antibody test results were positive. Medication-derived hemolytic anemia testing was conducted, but the presence of positive D-L antibody makes the test results inconclusive. This ultimately led to a diagnosis of paroxysmal cold hemoglobinuria (PCH), presumably triggered by a viral syndrome. Convalescent titers to Mycoplasma were not checked given clinical improvement. Because the patient’s hemoglobin was stable during hospitalization, he was not treated with steroids. His parents were counseled on avoiding cold temperatures for several days. Within 1 month, his hemoglobin had recovered without further evidence of hemolysis.

Hemolytic anemia refers to the accelerated destruction of red blood cells and can be further classified as acquired or hereditary.¹ Hereditary conditions causing hemolytic anemia include enzymopathies (eg, glucose-6-phosphate dehydrogenase deficiency), hemoglobinopathies (eg, sickle cell disease), and membrane abnormalities (eg, hereditary spherocytosis). Acquired pathologies include microangiopathic hemolytic anemia (MAHA), anemias directly caused by certain infections such as malaria, and immune-mediated (Coombs-positive) hemolytic anemias.

MAHA can sometimes be life-threatening and is therefore important to identify quickly. In the right clinical context, such processes may be rapidly recognized by the presence of schistocytes on blood smear in addition to an elevated serum LDH level. Schistocytes suggest mechanical destruction of erythrocytes in the vasculature, the hallmark of MAHA. Important MAHAs include thrombocytopenic purpura, hemolytic-uremic syndrome, and disseminated intravascular coagulation. Though this patient did have a mildly elevated LDH, MAHA was less likely because there were no schistocytes on the blood smear.

Autoimmune hemolytic anemias (AIHAs) are another important subset of acquired hemolytic anemias. AIHAs occur when there is antibody-mediated destruction of erythrocytes. The direct Coombs test evaluates for antibody- or complement-­coated erythrocytes. After administration of anti-IgG and anti-­C3 serum, the test evaluates for agglutination of the red cells caused by attached antibodies or complement. Coombs-­positive AIHA can also be categorized by the temperature of agglutination. “Warm” hemolysis often involves IgG autoantibodies (ie, warm agglutinins), while “cold” antibodies, usually IgM autoantibodies, bind at colder temperatures (0-4 °C) and activate complements, including C3. In this patient, the Coombs C3 was positive while the Coombs IgG was negative, which is more suggestive of a cold complement–mediated pathway.

Cold AIHA can be further categorized into primary cold agglutinin disease, secondary cold agglutinin disease, and PCH. Primary cold agglutinin disease is an autoimmune disorder that mostly occurs in adults. Secondary cold AIHA can often be triggered by bacterial infection (commonly M pneumoniae) or viruses including EBV, measles, and mumps.² Medications, including penicillin and cephalosporins, can also be implicated. Secondary cold AIHA is also linked with autoimmune diseases, such as systemic lupus erythematosus and lymphoproliferative disorders. PCH can be identified with the unique presence of a specific autoantibody (ie, D-L autoantibody) that agglutinates at cold temperatures but dissociates on subsequent rewarming.³ Complement remains affixed and activates hemolysis.

The D-L antibody responsible for PCH is an IgG antibody to the P-antigen present on the erythrocyte surface. Since the Coombs test is conducted at normal temperature, it will be positive for the affixed complement but not for IgG. The underlying mechanism for PCH was proposed by Julius Donath, MD, and Karl Landsteiner, MD, in 1904 and is considered to be the first description of autoimmune disease being precipitated by antibodies.⁴ The D-L antibody test itself is uncommonly performed and somewhat difficult to interpret, particularly in adults, and may lead to false-negative results.⁵

PCH is an acquired, cold AIHA more common to children^6,7 and may account for up to 33% of pediatric AIHA cases.⁸ Typical presentation is after an upper respiratory tract illness; however, the trigger is often not identified. Implicated triggers include a number of viruses.⁹ Clinical presentation includes findings of intravascular hemolysis similar to those in our patient. The pathogenic IgG autoantibody is polyclonal and is likely formed because of immune stimulation, which is consistent with the predominance of nonmalignant triggers of this disease process.¹⁰ Hemolysis and associated symptoms are often exacerbated with cold exposure; both typically resolve within 2 weeks. In recurrent cases, which are a minority, immunosuppression may be considered.¹⁰

PCH remains an often-understated cause of hemolytic anemia particularly in children. Lacking obvious pathognomonic clinical symptoms, it may be overlooked for other forms of AIHA or MAHA. However, with a structured approach to evaluation, as with this patient who had hematuria and jaundice, early diagnosis can prevent an unnecessarily extensive workup and can provide reassurance to patient and parents. By understanding the basic categories of hemolytic anemia, the relevant blood testing available, and interpretation of Coombs test results, clinicians can ensure that PCH is a diagnosis that is not left out in the cold.

• Examination for schistocytes on a blood smear can help identify life-threatening causes of hemolytic anemia.
• Characterization of cold AIHA includes defining the underlying etiology as primary cold agglutinin disease, secondary cold agglutinin disease, or PCH.
• PCH is a cold AIHA that is an underrecognized cause of hemolytic anemia in children. The diagnosis of PCH is made by testing for the presence of the D-L antibody.

A previously healthy 4-year-old boy presented to his pediatrician for nasal congestion, left ear pain, and intermittent fevers, which he’d been experiencing for 2 days. His exam was consistent with acute otitis media. Cefdinir was prescribed given a rash allergy to amoxicillin. His fever, congestion, and otalgia improved the next day.

Three days later he developed abdominal pain, fever, and labored breathing; his mother brought him to the emergency department (ED). His temperature was 38.0 °C, heart rate 141 beats per minute, blood pressure 117/71 mm Hg, respiratory rate 22 breaths per minute; he had oxygen saturation of 96% on ambient air. Despite mild accessory muscle use, he appeared comfortable and interactive. His left tympanic membrane was bulging without erythema. His neck was supple and mucous membranes moist. He had neither cervical lymphadenopathy nor conjunctival pallor. The cardiopulmonary exam was normal except for tachycardia. His abdomen was soft and not distended without organomegaly or tenderness.

Upper respiratory tract symptoms are commonly encountered in pediatrics and most often result from self-limited viral processes. Evaluation of a child with upper respiratory tract symptoms aims to identify serious causes like meningitis, as well as assessing the need for antimicrobial therapy. Supportive management is often appropriate in otitis media. His new, more concerning symptoms portend either a progression of the original process causing his upper respiratory tract symptoms or a separate etiology. It is key to determine which signs and symptoms are associated with the primary process and which are compensatory or secondary. If he were to be more ill appearing, for example, it is possible that his respiratory distress may be related to an underlying systemic illness rather than a primary lung process. Respiratory distress, abdominal pain, and fever could be a result of sepsis from an intrabdominal process such as ruptured appendicitis, intussusception, or malrotation with volvulus. Other causes of sepsis, such as meningitis or severe mastoiditis, both rare complications of otitis media, should be considered, although he does not appear severely ill. Acute myelogenous leukemia or other malignancies and illnesses associated with immunodeficiency can present with sepsis and chloromas in the middle ear that can be misconstrued as otitis media.

A chest radiograph demonstrated left lower lobe patchy opacities concerning for pneumonia. Rapid respiratory syncytial virus and influenza antigen test results were negative. Laboratory testing for general bloodwork was not obtained. He was administered a single dose of intramuscular ceftriaxone, prescribed a 5-day course of azithromycin, and discharged home. The child’s breathing gradually improved, but he continued to have subjective fevers. Two days later, he developed dark red urine. His mother brought him back to the outpatient clinic.

At the time of the ED visit, a diagnosis of community-acquired pneumonia was plausible given fever, mildly increased work of breathing, and an opacification on chest radiography. Most community-acquired pneumonia is caused by viruses; common bacterial causes for his age include Streptococcus pneumoniae and Moraxella catarrhalis. The first-line treatment for uncomplicated community-acquired pneumonia in children is amoxicillin, but this was appropriately avoided given his allergy.

The persistent fevers are surprising. The improvement in breathing corresponds to the treatment (and resolution) of community-acquired pneumonia. However, the development of dark urine does not. Red urine—in the absence of ingested pigments (such as those found in beets)—usually results from hematuria, hemoglobinuria, or myoglobinuria. Gross hematuria can originate from the kidneys to the urethral meatus. Abdominal masses, kidney trauma, or underlying kidney disease may all present with gross hematuria (or microscopic hematuria, seen only on urinalysis). The urine should be examined for the presence of heme, protein, and for evidence of infection; microscopy should be performed to examine for cellular casts and dysmorphic red cells. Tests of renal function, a comprehensive metabolic panel, evaluation of hematologic indexes, and assessments of inflammatory markers should be performed.

The child lived with his parents and had no siblings. He experienced no physical trauma, and there was no family history of kidney disease or hematuria. His father had a persistent cough and fever for 1 month, but recovered around the time the patient began to experience his initial symptoms. This was the patient’s third diagnosis of pneumonia. He had not traveled and was up to date with immunizations. He attended day care.

The fact that this is not the first episode of “pneumonia” raises important possibilities. The most likely one is that the child has had multiple viral infections; however, he could have an underlying primary immunodeficiency (PI) that predisposes him to recurrent infections. More severe PIs often present with recurrent sepsis, bacteremia, and failure to thrive, none of which were present in this case. Less severe PIs (such as selective IgA deficiency) could be possible. Another possibility is that these recurrent episodes of pneumonia are a relapsing and remitting noninfectious process, such as an antineutrophil cytoplasmic antibodies–associated vasculitis or anti–glomerular basement membrane disease. The patient’s father’s recent prolonged respiratory symptoms may be suggestive of pertussis or a “walking pneumonia” potentially caused by Mycoplasma or another atypical bacterium.

His temperature was 36.9 °C, heart rate 107 beats per minute, blood pressure was 106/67 mm Hg, and respiratory rate was 24 breaths per minute with oxygen saturation of 100% on ambient air. He was well appearing. His mucous membranes were moist, and oropharynx was clear. He had scleral icterus. The cardiopulmonary exam was normal. He had no significant lymphadenopathy, hepatosplenomegaly, or rashes.

The finding of jaundice is an important diagnostic pivot point, especially when combined with hematuria. The next step is determining if the jaundice is resulting from unconjugated or conjugated hyperbilirubinemia; the former most often stems from hemolysis or impairment in conjugation, while the latter results from intrahepatic or extrahepatic biliary defects. Tests for hepatobiliary injury including evaluations of alanine and aspartate aminotransferases and alkaline phosphatase, as well as for hepatic function such as tests of coagulation, should be performed.

The patient was referred to the ED and admitted for further evaluation. A complete blood count revealed a white blood cell (WBC) count of 10,700/µL (61% polymorphonuclear neutrophils, 30% lymphocytes, 5% monocytes, 3% eosinophils, 1% basophils), hemoglobin count was 10.3 g/dL (reticulocyte 2% with absolute reticulocyte count 58,400/μL), and platelet count was 265,000/µL. Components of the basic metabolic panel were within reference ranges except for a mildly elevated blood urea nitrogen level of 14 mg/dL with normal creatinine level of 0.3 mg/dL. Total protein was 6.7 g/dL (reference range, 6.4-8.3) and albumin 3.9 g/dL (reference range, 3.4-4.8). Alkaline phosphatase level was 188 U/L (reference range, 44-147), aspartate aminotransferase level 76 U/L (reference range, 0-40), and alanine aminotransferase level 12 U/L (reference range, 7-40). Total bilirubin level was 2.4 mg/dL (reference range, less than 1.5) with direct bilirubin level of 0.4 mg/dL. His C-reactive protein level was 1.5 mg/mL (reference range, 0-0.75). Creatinine kinase (CK) level was 2,550 U/L (reference range, 2-198). International Normalized Ratio (INR) was 1.0. Urinalysis was notable for 2+ proteinuria, large hemoglobin pigment, and 6 red blood cells per high power field (reference range, 0-4).

His blood urea nitrogen is elevated, reflecting either prerenal azotemia or increased absorption of nitrogenous products. Unconjugated hyperbilirubinemia may result from impaired hepatic bilirubin uptake (such as in heart failure or portosystemic shunts), impaired bilirubin conjugation (resulting from genetic conditions or drugs), or excess bilirubin production (such as in hemolysis); his anemia and lack of other evidence of hepatic dysfunction point to hemolysis as the etiology. The reticulocyte production index is approximately 1%, which suggests that an increase in erythrocyte generation is present but inadequate. This, however, does not mean that an erythrocyte production abnormality is present since reticulocytosis can be delayed in many cases of acute hemolytic anemia. It is also possible that the same hemolytic process is affecting mature and immature erythrocytes. A peripheral blood smear should be reviewed for evidence of intravascular hemolysis and testing for autoimmune hemolysis should be performed. Notably, his white blood cell and platelet counts are preserved, which makes a bone marrow–involved malignancy or infiltrative process less likely. The alkaline phosphatase elevation may result from either intrahepatic or extrahepatic biliopathy; bone damage is also possible. The elevation of aspartate aminotransferase, CK, and potassium, along with marked urinary heme pigment, may indicate muscle damage; the most common myositis in children is benign acute childhood myositis resulting from viral infection. However, the moderate level of CK elevation seen in this case is nonspecific and can result from many different etiologies. A metabolic myopathy, such as carnitine palmitoyltransferase II deficiency, can be made worse by metabolic stress and result in rhabdomyolysis; the presentations of inborn errors of metabolism are varied and a planned-out, stepwise approach in evaluation is fundamental.

Lactic acid dehydrogenase (LDH) level was 1,457 U/L (reference range, 140-280), and haptoglobin level was less than 6 mg/dL (reference range, 30-200). Peripheral blood smear demonstrated occasional atypical, reactive-appearing lymphocytes with red cell clumping and agglutination, as well as rare target, burr, and fragmented red cells. Test results for urine myoglobin were negative. Results of urine culture were negative. No blood culture was collected.

The elevated LDH, decreased haptoglobin, and findings on the peripheral blood smear confirm hemolysis. The clumping of erythrocytes can be artifactual in the preparation of peripheral smears, but when considered in the context of hemolysis, may be clinically important. Clumping of erythrocytes on the peripheral smear indicates the binding of a protein to antigens on the erythrocyte membrane; when this occurs below body temperature, this is consistent with the presence of a “cold agglutinin,” usually an IgM antibody directed at erythrocyte surface antigens that causes agglutination and destruction, especially in cooler areas of the body. This is a well-known complication of Mycoplasma pneumoniae infections as well as Epstein-Barr virus (EBV) infections; it may also occur with lymphoid malignancies or autoimmune disease.

Direct Coombs IgG test findings were negative, direct Coombs C3 test was positive, and direct Coombs polyspecific test was positive. M pneumoniae IgG antibody level was 1.4 mg/dL (reference ranges: <0.9, negative; 0.91-1.09, equivocal; >1.1, positive); M pneumoniae IgM level was 529 U/mL (reference range: <770, negative). EBV capsid IgM and IgG levels were undetectable. EBV nuclear antigen IgG level was also undetectable. EBV viral load was fewer than 10 copies/mL. Antinuclear antibodies (ANA) level was negative. General IgE and IgM levels were normal, at 11 and 81 mg/dL, respectively. Repeat complete blood count showed WBC of 7,800/µL, hemoglobin of 8.7 g/dL, and platelet count of 341,000/µL. The patient’s hemoglobin remained stable during hospitalization.

This directed testing is helpful in further classifying the patient’s hemolytic anemia. Autoimmune hemolytic anemias are classified into warm antibody–mediated, cold antibody–mediated, and mixed-type forms; drug-induced and alloimmune hemolytic anemias also occur. In addition, both systemic lupus erythematosus and antiphospholipid antibody syndrome can have hemolytic anemia with variable Coombs testing results; neither fit well in this case. The absence of red blood cell–directed IgG antibodies substantially decreases the likelihood of warm antibody–mediated hemolytic anemia. In cold antibody–mediated hemolytic anemia, antibodies bind to the erythrocyte membrane and then adhere to complement C3, which leads to both intravascular and extravascular hemolysis. Important types of cold antibody–mediated hemolytic anemia in children are primary and secondary cold agglutinin disease, along with paroxysmal cold hemoglobinuria. The Donath-Landsteiner test can be helpful in differentiating these conditions. Antibodies to Mycoplasma may be delayed in response to acute infection, and a child who is reinfected may only produce IgG antibodies. Given the patient’s clinical stability and previous health, the most likely diagnosis is Mycoplasma-induced cold antibody–mediated hemolytic anemia. It may be helpful to check convalescent titers to Mycoplasma in 2 to 4 weeks.

Donath-Landsteiner (D-L) antibody test results were positive. Medication-derived hemolytic anemia testing was conducted, but the presence of positive D-L antibody makes the test results inconclusive. This ultimately led to a diagnosis of paroxysmal cold hemoglobinuria (PCH), presumably triggered by a viral syndrome. Convalescent titers to Mycoplasma were not checked given clinical improvement. Because the patient’s hemoglobin was stable during hospitalization, he was not treated with steroids. His parents were counseled on avoiding cold temperatures for several days. Within 1 month, his hemoglobin had recovered without further evidence of hemolysis.

Hemolytic anemia refers to the accelerated destruction of red blood cells and can be further classified as acquired or hereditary.¹ Hereditary conditions causing hemolytic anemia include enzymopathies (eg, glucose-6-phosphate dehydrogenase deficiency), hemoglobinopathies (eg, sickle cell disease), and membrane abnormalities (eg, hereditary spherocytosis). Acquired pathologies include microangiopathic hemolytic anemia (MAHA), anemias directly caused by certain infections such as malaria, and immune-mediated (Coombs-positive) hemolytic anemias.

MAHA can sometimes be life-threatening and is therefore important to identify quickly. In the right clinical context, such processes may be rapidly recognized by the presence of schistocytes on blood smear in addition to an elevated serum LDH level. Schistocytes suggest mechanical destruction of erythrocytes in the vasculature, the hallmark of MAHA. Important MAHAs include thrombocytopenic purpura, hemolytic-uremic syndrome, and disseminated intravascular coagulation. Though this patient did have a mildly elevated LDH, MAHA was less likely because there were no schistocytes on the blood smear.

Autoimmune hemolytic anemias (AIHAs) are another important subset of acquired hemolytic anemias. AIHAs occur when there is antibody-mediated destruction of erythrocytes. The direct Coombs test evaluates for antibody- or complement-­coated erythrocytes. After administration of anti-IgG and anti-­C3 serum, the test evaluates for agglutination of the red cells caused by attached antibodies or complement. Coombs-­positive AIHA can also be categorized by the temperature of agglutination. “Warm” hemolysis often involves IgG autoantibodies (ie, warm agglutinins), while “cold” antibodies, usually IgM autoantibodies, bind at colder temperatures (0-4 °C) and activate complements, including C3. In this patient, the Coombs C3 was positive while the Coombs IgG was negative, which is more suggestive of a cold complement–mediated pathway.

Cold AIHA can be further categorized into primary cold agglutinin disease, secondary cold agglutinin disease, and PCH. Primary cold agglutinin disease is an autoimmune disorder that mostly occurs in adults. Secondary cold AIHA can often be triggered by bacterial infection (commonly M pneumoniae) or viruses including EBV, measles, and mumps.² Medications, including penicillin and cephalosporins, can also be implicated. Secondary cold AIHA is also linked with autoimmune diseases, such as systemic lupus erythematosus and lymphoproliferative disorders. PCH can be identified with the unique presence of a specific autoantibody (ie, D-L autoantibody) that agglutinates at cold temperatures but dissociates on subsequent rewarming.³ Complement remains affixed and activates hemolysis.

The D-L antibody responsible for PCH is an IgG antibody to the P-antigen present on the erythrocyte surface. Since the Coombs test is conducted at normal temperature, it will be positive for the affixed complement but not for IgG. The underlying mechanism for PCH was proposed by Julius Donath, MD, and Karl Landsteiner, MD, in 1904 and is considered to be the first description of autoimmune disease being precipitated by antibodies.⁴ The D-L antibody test itself is uncommonly performed and somewhat difficult to interpret, particularly in adults, and may lead to false-negative results.⁵

PCH is an acquired, cold AIHA more common to children^6,7 and may account for up to 33% of pediatric AIHA cases.⁸ Typical presentation is after an upper respiratory tract illness; however, the trigger is often not identified. Implicated triggers include a number of viruses.⁹ Clinical presentation includes findings of intravascular hemolysis similar to those in our patient. The pathogenic IgG autoantibody is polyclonal and is likely formed because of immune stimulation, which is consistent with the predominance of nonmalignant triggers of this disease process.¹⁰ Hemolysis and associated symptoms are often exacerbated with cold exposure; both typically resolve within 2 weeks. In recurrent cases, which are a minority, immunosuppression may be considered.¹⁰

PCH remains an often-understated cause of hemolytic anemia particularly in children. Lacking obvious pathognomonic clinical symptoms, it may be overlooked for other forms of AIHA or MAHA. However, with a structured approach to evaluation, as with this patient who had hematuria and jaundice, early diagnosis can prevent an unnecessarily extensive workup and can provide reassurance to patient and parents. By understanding the basic categories of hemolytic anemia, the relevant blood testing available, and interpretation of Coombs test results, clinicians can ensure that PCH is a diagnosis that is not left out in the cold.

• Examination for schistocytes on a blood smear can help identify life-threatening causes of hemolytic anemia.
• Characterization of cold AIHA includes defining the underlying etiology as primary cold agglutinin disease, secondary cold agglutinin disease, or PCH.
• PCH is a cold AIHA that is an underrecognized cause of hemolytic anemia in children. The diagnosis of PCH is made by testing for the presence of the D-L antibody.

The story of the coronavirus disease 2019 (COVID-19) pandemic in the United States has been defined, in part, by a persistent shortage of medical supplies that has made it difficult and dangerous for healthcare workers to care for infected patients. States, health systems, and even individual hospitals are currently competing against one another—sometimes at auction—to obtain personal protective equipment (PPE). This “Wild West” scenario has resulted in bizarre stories involving attempts to obtain PPE. One health system recently described a James Bond–like pursuit of essential PPE, complete with a covert trip to an industrial warehouse, trucks filled with masks but labeled as food delivery vehicles, and an intervention by a United States congressman.¹ Many states have experienced analogous, but still atypical, stories: masks flown in from China using the private jet of a professional sports team owner,² widespread use of novel sterilization modalities to allow PPE reuse,³ and one attempt to purchase price-gouged PPE from the host of the show “Shark Tank.”⁴ In some cases, hospitals and healthcare workers have pleaded for PPE on fundraising and social media sites.⁵

These profound deviations from operations of contemporary health system supply chains would have seemed beyond belief just a few months ago. Instead, they now echo the collective experiences of healthcare stakeholders trying to obtain PPE to protect their frontline healthcare workers during the COVID-19 pandemic.

How did we get into this situation? The manufacture of medical supplies like gowns and masks is a highly competitive business with very slim margins, and as a result, medical equipment manufacturers aim to match their supply with the market’s demand, with hospitals and health systems using just-in-time ordering to limit excess inventory.⁶ While this approach adds efficiency and reduces costs, it also renders manufacturers and customers vulnerable to supply disruptions and shortages when need surges. The COVID-19 pandemic represents perhaps the most extreme example of a massive, widespread surge in demand that occurred multifocally and in a highly compressed time frame. Unlike other industries (eg, consumer paper products), however, in which demand exceeding supply causes inconvenience, the lack of PPE has led to critical public health consequences, with lives of both healthcare workers and vulnerable patients lost because of these shortages of medical equipment.

There are many reasons for the PPE crisis. As noted above, manufacturers have prioritized efficiency over the ability to quickly increase production. They adhere to just-in-time ordering rather than planning for a surge in demand with extra production capacity, all to avoid having warehouses filled with unsold products if surges never occur. This strategy, compounded by the fact that most PPE in the United States is imported from areas in Asia that were profoundly affected early on by COVID-19, led to the observed widespread shortages. When PPE became unavailable from usual suppliers, hospitals were unable to locate other sources of existing PPE because of a lack of transparency about where PPE could be found and how it could be obtained. The Food and Drug Administration and other federal regulatory agencies maintained strict regulations around PPE production and, despite the crisis, made few exceptions.⁷ The FDA did grant a few Emergency Use Authorizations (EUAs) for certain improvised, decontaminated, or alternative respirators (eg, the Chinese-made KN95), but it has only very infrequently issued EUAs to allow domestic manufacturers to ramp up production.⁸ These failures were accompanied by an serious increase in PPE use, leading to spikes in price, price gouging, and hoarding,⁹ problems that were further magnified as health systems and hospitals were forced to compete with nonhealthcare businesses for PPE.

The Defense Production Act (DPA) gives the federal government the power to increase production of goods needed during a crisis⁸ to offer purchasing guarantees, coordinate federal agencies, and regulate distribution and pricing. However, the current administration’s failure to mount a coordinated federal response has contributed to the observed market instability, medical supply shortages, and public health crisis we face. We have previously recommended that the federal government use the power of the DPA to reduce manufacturers’ risk of being uncompensated for excess supply, support temporary reductions in regulatory barriers, and create mandatory centralized reporting of PPE supply, including completed PPE and its components.¹⁰ We stand by these recommendations but also acknowledge that hospitals and health systems may be simultaneously considering how to best prepare for future crises and even surges in demand over the next 18 months as the COVID-19 pandemic continues.

1. Encourage mandates at the hospital, health system, and state level regarding minimum inventory levels for essential equipment. Stockpiles are essential for emergency preparedness. In the long term, these sorts of stockpiles are economically infeasible without government help to maintain them. In the near term, however, it is sensible that hospitals and health systems would maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases. However, a soon-to-published study suggests that over 40% of hospitals had a PPE stockpile of less than 2 weeks.¹¹ Although this survey was conducted at the height of the shortage, it suggests that there is opportunity for improvement.

2. Coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution. The best example of this is the seven-state purchasing consortium announced by New York Governor Andrew Cuomo in early May.¹² Unfortunately, since the announcement, there have been few details about whether the states were successful in their effort to reduce prices or to obtain PPE in bulk. Still, hospitals and health systems could join or emulate purchasing collaboratives to allow resources to be better allocated according to need. There are barriers to such collaboratives because the market is currently set up to encourage competition among health systems and hospitals. During the pandemic, however, cooperation has increasingly been favored over competition in science and healthcare delivery. There are also existing hospital purchasing collaboratives (eg, Premier, Inc¹³), which have taken steps to vet suppliers and improve access to PPE, but it is not clear how successful these efforts have been to date.

3. Advocate for strong federal leadership, including support for increased domestic manufacturing; replenishment and maintenance of state and health system stockpiles of PPE, ventilators, and medications; and development of a centrally coordinated PPE allocation and distribution process. While hospitals and health systems may favor remaining as apolitical as possible, the need for a federal response to stabilize the PPE market may be too urgent and necessary to ignore.

As hospitals and health systems prepare for continued surges in COVID-19 cases, they face challenges in providing PPE for frontline clinicians and staff. A federal plan to enhance nimbleness in responding to multifocal, geographic outbreaks and ensure awareness regarding inventory would improve our chances to successfully navigate the next pandemic and optimize the protection of our health workers, patients, and public health. In the absence of such a plan, hospitals should maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases and should continue to attempt to coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution.

The story of the coronavirus disease 2019 (COVID-19) pandemic in the United States has been defined, in part, by a persistent shortage of medical supplies that has made it difficult and dangerous for healthcare workers to care for infected patients. States, health systems, and even individual hospitals are currently competing against one another—sometimes at auction—to obtain personal protective equipment (PPE). This “Wild West” scenario has resulted in bizarre stories involving attempts to obtain PPE. One health system recently described a James Bond–like pursuit of essential PPE, complete with a covert trip to an industrial warehouse, trucks filled with masks but labeled as food delivery vehicles, and an intervention by a United States congressman.¹ Many states have experienced analogous, but still atypical, stories: masks flown in from China using the private jet of a professional sports team owner,² widespread use of novel sterilization modalities to allow PPE reuse,³ and one attempt to purchase price-gouged PPE from the host of the show “Shark Tank.”⁴ In some cases, hospitals and healthcare workers have pleaded for PPE on fundraising and social media sites.⁵

These profound deviations from operations of contemporary health system supply chains would have seemed beyond belief just a few months ago. Instead, they now echo the collective experiences of healthcare stakeholders trying to obtain PPE to protect their frontline healthcare workers during the COVID-19 pandemic.

How did we get into this situation? The manufacture of medical supplies like gowns and masks is a highly competitive business with very slim margins, and as a result, medical equipment manufacturers aim to match their supply with the market’s demand, with hospitals and health systems using just-in-time ordering to limit excess inventory.⁶ While this approach adds efficiency and reduces costs, it also renders manufacturers and customers vulnerable to supply disruptions and shortages when need surges. The COVID-19 pandemic represents perhaps the most extreme example of a massive, widespread surge in demand that occurred multifocally and in a highly compressed time frame. Unlike other industries (eg, consumer paper products), however, in which demand exceeding supply causes inconvenience, the lack of PPE has led to critical public health consequences, with lives of both healthcare workers and vulnerable patients lost because of these shortages of medical equipment.

There are many reasons for the PPE crisis. As noted above, manufacturers have prioritized efficiency over the ability to quickly increase production. They adhere to just-in-time ordering rather than planning for a surge in demand with extra production capacity, all to avoid having warehouses filled with unsold products if surges never occur. This strategy, compounded by the fact that most PPE in the United States is imported from areas in Asia that were profoundly affected early on by COVID-19, led to the observed widespread shortages. When PPE became unavailable from usual suppliers, hospitals were unable to locate other sources of existing PPE because of a lack of transparency about where PPE could be found and how it could be obtained. The Food and Drug Administration and other federal regulatory agencies maintained strict regulations around PPE production and, despite the crisis, made few exceptions.⁷ The FDA did grant a few Emergency Use Authorizations (EUAs) for certain improvised, decontaminated, or alternative respirators (eg, the Chinese-made KN95), but it has only very infrequently issued EUAs to allow domestic manufacturers to ramp up production.⁸ These failures were accompanied by an serious increase in PPE use, leading to spikes in price, price gouging, and hoarding,⁹ problems that were further magnified as health systems and hospitals were forced to compete with nonhealthcare businesses for PPE.

The Defense Production Act (DPA) gives the federal government the power to increase production of goods needed during a crisis⁸ to offer purchasing guarantees, coordinate federal agencies, and regulate distribution and pricing. However, the current administration’s failure to mount a coordinated federal response has contributed to the observed market instability, medical supply shortages, and public health crisis we face. We have previously recommended that the federal government use the power of the DPA to reduce manufacturers’ risk of being uncompensated for excess supply, support temporary reductions in regulatory barriers, and create mandatory centralized reporting of PPE supply, including completed PPE and its components.¹⁰ We stand by these recommendations but also acknowledge that hospitals and health systems may be simultaneously considering how to best prepare for future crises and even surges in demand over the next 18 months as the COVID-19 pandemic continues.

1. Encourage mandates at the hospital, health system, and state level regarding minimum inventory levels for essential equipment. Stockpiles are essential for emergency preparedness. In the long term, these sorts of stockpiles are economically infeasible without government help to maintain them. In the near term, however, it is sensible that hospitals and health systems would maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases. However, a soon-to-published study suggests that over 40% of hospitals had a PPE stockpile of less than 2 weeks.¹¹ Although this survey was conducted at the height of the shortage, it suggests that there is opportunity for improvement.

2. Coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution. The best example of this is the seven-state purchasing consortium announced by New York Governor Andrew Cuomo in early May.¹² Unfortunately, since the announcement, there have been few details about whether the states were successful in their effort to reduce prices or to obtain PPE in bulk. Still, hospitals and health systems could join or emulate purchasing collaboratives to allow resources to be better allocated according to need. There are barriers to such collaboratives because the market is currently set up to encourage competition among health systems and hospitals. During the pandemic, however, cooperation has increasingly been favored over competition in science and healthcare delivery. There are also existing hospital purchasing collaboratives (eg, Premier, Inc¹³), which have taken steps to vet suppliers and improve access to PPE, but it is not clear how successful these efforts have been to date.

3. Advocate for strong federal leadership, including support for increased domestic manufacturing; replenishment and maintenance of state and health system stockpiles of PPE, ventilators, and medications; and development of a centrally coordinated PPE allocation and distribution process. While hospitals and health systems may favor remaining as apolitical as possible, the need for a federal response to stabilize the PPE market may be too urgent and necessary to ignore.

As hospitals and health systems prepare for continued surges in COVID-19 cases, they face challenges in providing PPE for frontline clinicians and staff. A federal plan to enhance nimbleness in responding to multifocal, geographic outbreaks and ensure awareness regarding inventory would improve our chances to successfully navigate the next pandemic and optimize the protection of our health workers, patients, and public health. In the absence of such a plan, hospitals should maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases and should continue to attempt to coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution.

The story of the coronavirus disease 2019 (COVID-19) pandemic in the United States has been defined, in part, by a persistent shortage of medical supplies that has made it difficult and dangerous for healthcare workers to care for infected patients. States, health systems, and even individual hospitals are currently competing against one another—sometimes at auction—to obtain personal protective equipment (PPE). This “Wild West” scenario has resulted in bizarre stories involving attempts to obtain PPE. One health system recently described a James Bond–like pursuit of essential PPE, complete with a covert trip to an industrial warehouse, trucks filled with masks but labeled as food delivery vehicles, and an intervention by a United States congressman.¹ Many states have experienced analogous, but still atypical, stories: masks flown in from China using the private jet of a professional sports team owner,² widespread use of novel sterilization modalities to allow PPE reuse,³ and one attempt to purchase price-gouged PPE from the host of the show “Shark Tank.”⁴ In some cases, hospitals and healthcare workers have pleaded for PPE on fundraising and social media sites.⁵

These profound deviations from operations of contemporary health system supply chains would have seemed beyond belief just a few months ago. Instead, they now echo the collective experiences of healthcare stakeholders trying to obtain PPE to protect their frontline healthcare workers during the COVID-19 pandemic.

How did we get into this situation? The manufacture of medical supplies like gowns and masks is a highly competitive business with very slim margins, and as a result, medical equipment manufacturers aim to match their supply with the market’s demand, with hospitals and health systems using just-in-time ordering to limit excess inventory.⁶ While this approach adds efficiency and reduces costs, it also renders manufacturers and customers vulnerable to supply disruptions and shortages when need surges. The COVID-19 pandemic represents perhaps the most extreme example of a massive, widespread surge in demand that occurred multifocally and in a highly compressed time frame. Unlike other industries (eg, consumer paper products), however, in which demand exceeding supply causes inconvenience, the lack of PPE has led to critical public health consequences, with lives of both healthcare workers and vulnerable patients lost because of these shortages of medical equipment.

There are many reasons for the PPE crisis. As noted above, manufacturers have prioritized efficiency over the ability to quickly increase production. They adhere to just-in-time ordering rather than planning for a surge in demand with extra production capacity, all to avoid having warehouses filled with unsold products if surges never occur. This strategy, compounded by the fact that most PPE in the United States is imported from areas in Asia that were profoundly affected early on by COVID-19, led to the observed widespread shortages. When PPE became unavailable from usual suppliers, hospitals were unable to locate other sources of existing PPE because of a lack of transparency about where PPE could be found and how it could be obtained. The Food and Drug Administration and other federal regulatory agencies maintained strict regulations around PPE production and, despite the crisis, made few exceptions.⁷ The FDA did grant a few Emergency Use Authorizations (EUAs) for certain improvised, decontaminated, or alternative respirators (eg, the Chinese-made KN95), but it has only very infrequently issued EUAs to allow domestic manufacturers to ramp up production.⁸ These failures were accompanied by an serious increase in PPE use, leading to spikes in price, price gouging, and hoarding,⁹ problems that were further magnified as health systems and hospitals were forced to compete with nonhealthcare businesses for PPE.

The Defense Production Act (DPA) gives the federal government the power to increase production of goods needed during a crisis⁸ to offer purchasing guarantees, coordinate federal agencies, and regulate distribution and pricing. However, the current administration’s failure to mount a coordinated federal response has contributed to the observed market instability, medical supply shortages, and public health crisis we face. We have previously recommended that the federal government use the power of the DPA to reduce manufacturers’ risk of being uncompensated for excess supply, support temporary reductions in regulatory barriers, and create mandatory centralized reporting of PPE supply, including completed PPE and its components.¹⁰ We stand by these recommendations but also acknowledge that hospitals and health systems may be simultaneously considering how to best prepare for future crises and even surges in demand over the next 18 months as the COVID-19 pandemic continues.

1. Encourage mandates at the hospital, health system, and state level regarding minimum inventory levels for essential equipment. Stockpiles are essential for emergency preparedness. In the long term, these sorts of stockpiles are economically infeasible without government help to maintain them. In the near term, however, it is sensible that hospitals and health systems would maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases. However, a soon-to-published study suggests that over 40% of hospitals had a PPE stockpile of less than 2 weeks.¹¹ Although this survey was conducted at the height of the shortage, it suggests that there is opportunity for improvement.

2. Coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution. The best example of this is the seven-state purchasing consortium announced by New York Governor Andrew Cuomo in early May.¹² Unfortunately, since the announcement, there have been few details about whether the states were successful in their effort to reduce prices or to obtain PPE in bulk. Still, hospitals and health systems could join or emulate purchasing collaboratives to allow resources to be better allocated according to need. There are barriers to such collaboratives because the market is currently set up to encourage competition among health systems and hospitals. During the pandemic, however, cooperation has increasingly been favored over competition in science and healthcare delivery. There are also existing hospital purchasing collaboratives (eg, Premier, Inc¹³), which have taken steps to vet suppliers and improve access to PPE, but it is not clear how successful these efforts have been to date.

3. Advocate for strong federal leadership, including support for increased domestic manufacturing; replenishment and maintenance of state and health system stockpiles of PPE, ventilators, and medications; and development of a centrally coordinated PPE allocation and distribution process. While hospitals and health systems may favor remaining as apolitical as possible, the need for a federal response to stabilize the PPE market may be too urgent and necessary to ignore.

As hospitals and health systems prepare for continued surges in COVID-19 cases, they face challenges in providing PPE for frontline clinicians and staff. A federal plan to enhance nimbleness in responding to multifocal, geographic outbreaks and ensure awareness regarding inventory would improve our chances to successfully navigate the next pandemic and optimize the protection of our health workers, patients, and public health. In the absence of such a plan, hospitals should maintain a minimum of 2 weeks’ worth of PPE to prepare for expected regional spikes in COVID-19 cases and should continue to attempt to coordinate efforts among states and health systems to collect and report inventory, regionalize resources, and coordinate their distribution.

When my grandfather, who speaks limited English, was admitted to a hospital following a stroke amid the coronavirus disease 2019 (COVID-19) pandemic, my family was understandably worried. Sure enough, within just hours of his admission, we were told our normally very calm and beloved Nana was experiencing significant agitation and delirium. He did not understand nurses’ efforts to calm him down, became even more confused, and was eventually sedated and placed in physical restraints. Even though my family’s presence might have prevented some or all of this terrible series of events, the hospital’s visiting policies during the wave of COVID-19 admissions meant that we were forced to wait in the parking lot as they transpired. The hospital’s policy at the time only allowed visitors for pediatrics, end-of-life care, or labor, not for patients with delirium or altered mental status. We were given the option to make a video call, but my grandfather’s stroke had almost completely taken away his vision. Instead of sitting by his side, comforting him, providing explanations in voices he knew and a language he understood, we were left imagining how difficult it must be to suddenly wake up in an unfamiliar environment, with strangers speaking a different language, limited vision, and your arms and legs tied. Intellectually, I understood the hospital’s goals to minimize transmission, but spiritually and emotionally, it felt very cruel and very wrong.

The next day, we successfully petitioned administration to make an exception for one visitor. We argued that our presence would allow for removal of the sedation and restraints. The clinical team agreed that video calls were insufficient in his situation; he was allowed a visitor. We decided that it should be my mother. As soon my grandfather heard her familiar voice, there was a dramatic improvement. He immediately became calmer and restraints were no longer necessary. The team was grateful for a better physical exam and my grandfather was more cooperative with physical therapy. A few days later, unfortunately, the hospital let us know that they had reevaluated their position on my mother’s visits and that she posed an unnecessary COVID-19 risk to medical staff and other patients. And as soon as she left, my grandfather was again agitated and confused for the remaining 3 days of his hospitalization. Although we are grateful that his delirium resolved once he returned home, delirium also has the potential to lead to long-term cognitive impairment.¹

The COVID-19 pandemic has required hospitals around the world to make difficult decisions about how to balance minimizing disease transmission with continuing to provide compassionate and high-quality patient care. Of these many dilemmas, developing flexible visitor policies is particularly difficult. Currently, the Centers for Disease Control and Prevention and many state health departments encourage limiting visitation in general but recognize the need for exceptions in special circumstances such as in end-of-life settings or altered mental status.^2-4

At the hospital level, there is substantial variation in visitation policies among hospitals. Near our family home in San Jose, California, one hospital currently allows visitation for pediatric patients, pregnant patients, end-of-life patients, surgical patients, and patients in the emergency department, as well as those with mental disabilities or safety needs.⁵ A mere 10 minutes away, another hospital has implemented a very different policy that allows only one visitor for pregnant patients and in end-of-life settings; there are no exceptions for patients with cognitive or physical disabilities.⁶ Other hospitals in the United States have gone even further, not permitting visitors even for those at the end of life.⁷ These patients are forced to spend their last few moments alone.

From an infection control perspective, there are certainly valid reasons to limit visitation. Even with temperature screenings, any movement into and out of a hospital poses a risk of transmitting disease. Infected but asymptomatic persons are known to transmit the disease. Additionally, hospitals still treat non–COVID-19 patients who are most susceptible to severe illness should they develop COVID-19 infection. Early in the COVID-19 pandemic, limitations in testing capacity, personal protective equipment (PPE), and staffing made it challenging to ensure safe visitation. In many cases, it was almost impossible to mitigate the transmission risk that visitors posed. Because many hospitals did not have the capacity to test all symptomatic patients, they could not reliably limit visits to COVID-19–positive patients. Additionally, without enough PPE for healthcare workers, hospitals could not afford for visitors to use additional PPE.

Now that testing is more readily available and some aspects of the PPE shortages have been addressed, we should not forget that visitation has significant benefits for both patients’ psychological well-being and their overall outcomes.⁸ Putting aside the emotional support that the physical presence of loved ones can offer, a large body of research indicates that allowing visitors can also meaningfully improve other important patient outcomes. Specifically, the presence of visitors is associated with less fear,⁹ reduced delirium,¹⁰ and even faster recovery.⁸ In many cases, family members can also help improve hospital safety surveillance and catch medical errors.¹¹

I saw firsthand how these benefits are particularly true for visitors who are also a patient’s primary caretaker. When my mother visited my grandfather, she was not simply a visitor but instead served as an active member of the care team. In addition to providing emotional comfort, my mother oriented him to his surroundings, successfully encouraged oral intake, and even caught some medication errors. Particularly for patients with cognitive impairment, caretakers know the patient better than anyone on the clinical team, and their absence can negatively affect the quality of care.

As a family member who also has familiarity with the healthcare system, I share hospitals’ concerns about wanting to minimize disease transmission. I recognize that, even with PPE and screenings, there is still a chance that visitors unknowingly spread COVID-19 to others in the hospital. On a personal level, however, it feels inhumane to maintain this policy even when it affects particularly vulnerable patients like my grandfather. As some hospitals are already doing,¹² we can take steps to allow visitors for such patients while minimizing the likelihood of COVID-19 disease transmission from visitors. Arriving visitors can be screened and required to wear PPE. While these measures may not eliminate the risk of COVID-19 transmission from visitors, they will likely reduce it significantly when implemented properly and make possible a more humane experience for all.¹³

Fortunately, my grandfather is now recovering comfortably at home, surrounded by his loved ones. To this day, however, he has not forgotten what it was like to be confused and alone in the hospital after his stroke. Even with loved ones around, a stroke is a profoundly distressing experience. To go through such an experience alone is even worse. Because of our petitioning, my grandfather was at least allowed a visitor for part of his stay. Other patients are not even allowed that. As we plan for the pandemic’s next waves, hospitals should reevaluate their visitor policies to ensure that their most vulnerable patients do not have to suffer alone.

The author sincerely thanks Dr Allan Goroll (Massachusetts General Hospital/Harvard Medical School) for his mentorship and critical review of this manuscript.

The author has nothing to disclose.

When my grandfather, who speaks limited English, was admitted to a hospital following a stroke amid the coronavirus disease 2019 (COVID-19) pandemic, my family was understandably worried. Sure enough, within just hours of his admission, we were told our normally very calm and beloved Nana was experiencing significant agitation and delirium. He did not understand nurses’ efforts to calm him down, became even more confused, and was eventually sedated and placed in physical restraints. Even though my family’s presence might have prevented some or all of this terrible series of events, the hospital’s visiting policies during the wave of COVID-19 admissions meant that we were forced to wait in the parking lot as they transpired. The hospital’s policy at the time only allowed visitors for pediatrics, end-of-life care, or labor, not for patients with delirium or altered mental status. We were given the option to make a video call, but my grandfather’s stroke had almost completely taken away his vision. Instead of sitting by his side, comforting him, providing explanations in voices he knew and a language he understood, we were left imagining how difficult it must be to suddenly wake up in an unfamiliar environment, with strangers speaking a different language, limited vision, and your arms and legs tied. Intellectually, I understood the hospital’s goals to minimize transmission, but spiritually and emotionally, it felt very cruel and very wrong.

The next day, we successfully petitioned administration to make an exception for one visitor. We argued that our presence would allow for removal of the sedation and restraints. The clinical team agreed that video calls were insufficient in his situation; he was allowed a visitor. We decided that it should be my mother. As soon my grandfather heard her familiar voice, there was a dramatic improvement. He immediately became calmer and restraints were no longer necessary. The team was grateful for a better physical exam and my grandfather was more cooperative with physical therapy. A few days later, unfortunately, the hospital let us know that they had reevaluated their position on my mother’s visits and that she posed an unnecessary COVID-19 risk to medical staff and other patients. And as soon as she left, my grandfather was again agitated and confused for the remaining 3 days of his hospitalization. Although we are grateful that his delirium resolved once he returned home, delirium also has the potential to lead to long-term cognitive impairment.¹

The COVID-19 pandemic has required hospitals around the world to make difficult decisions about how to balance minimizing disease transmission with continuing to provide compassionate and high-quality patient care. Of these many dilemmas, developing flexible visitor policies is particularly difficult. Currently, the Centers for Disease Control and Prevention and many state health departments encourage limiting visitation in general but recognize the need for exceptions in special circumstances such as in end-of-life settings or altered mental status.^2-4

At the hospital level, there is substantial variation in visitation policies among hospitals. Near our family home in San Jose, California, one hospital currently allows visitation for pediatric patients, pregnant patients, end-of-life patients, surgical patients, and patients in the emergency department, as well as those with mental disabilities or safety needs.⁵ A mere 10 minutes away, another hospital has implemented a very different policy that allows only one visitor for pregnant patients and in end-of-life settings; there are no exceptions for patients with cognitive or physical disabilities.⁶ Other hospitals in the United States have gone even further, not permitting visitors even for those at the end of life.⁷ These patients are forced to spend their last few moments alone.

From an infection control perspective, there are certainly valid reasons to limit visitation. Even with temperature screenings, any movement into and out of a hospital poses a risk of transmitting disease. Infected but asymptomatic persons are known to transmit the disease. Additionally, hospitals still treat non–COVID-19 patients who are most susceptible to severe illness should they develop COVID-19 infection. Early in the COVID-19 pandemic, limitations in testing capacity, personal protective equipment (PPE), and staffing made it challenging to ensure safe visitation. In many cases, it was almost impossible to mitigate the transmission risk that visitors posed. Because many hospitals did not have the capacity to test all symptomatic patients, they could not reliably limit visits to COVID-19–positive patients. Additionally, without enough PPE for healthcare workers, hospitals could not afford for visitors to use additional PPE.

Now that testing is more readily available and some aspects of the PPE shortages have been addressed, we should not forget that visitation has significant benefits for both patients’ psychological well-being and their overall outcomes.⁸ Putting aside the emotional support that the physical presence of loved ones can offer, a large body of research indicates that allowing visitors can also meaningfully improve other important patient outcomes. Specifically, the presence of visitors is associated with less fear,⁹ reduced delirium,¹⁰ and even faster recovery.⁸ In many cases, family members can also help improve hospital safety surveillance and catch medical errors.¹¹

I saw firsthand how these benefits are particularly true for visitors who are also a patient’s primary caretaker. When my mother visited my grandfather, she was not simply a visitor but instead served as an active member of the care team. In addition to providing emotional comfort, my mother oriented him to his surroundings, successfully encouraged oral intake, and even caught some medication errors. Particularly for patients with cognitive impairment, caretakers know the patient better than anyone on the clinical team, and their absence can negatively affect the quality of care.

As a family member who also has familiarity with the healthcare system, I share hospitals’ concerns about wanting to minimize disease transmission. I recognize that, even with PPE and screenings, there is still a chance that visitors unknowingly spread COVID-19 to others in the hospital. On a personal level, however, it feels inhumane to maintain this policy even when it affects particularly vulnerable patients like my grandfather. As some hospitals are already doing,¹² we can take steps to allow visitors for such patients while minimizing the likelihood of COVID-19 disease transmission from visitors. Arriving visitors can be screened and required to wear PPE. While these measures may not eliminate the risk of COVID-19 transmission from visitors, they will likely reduce it significantly when implemented properly and make possible a more humane experience for all.¹³

Fortunately, my grandfather is now recovering comfortably at home, surrounded by his loved ones. To this day, however, he has not forgotten what it was like to be confused and alone in the hospital after his stroke. Even with loved ones around, a stroke is a profoundly distressing experience. To go through such an experience alone is even worse. Because of our petitioning, my grandfather was at least allowed a visitor for part of his stay. Other patients are not even allowed that. As we plan for the pandemic’s next waves, hospitals should reevaluate their visitor policies to ensure that their most vulnerable patients do not have to suffer alone.

The author sincerely thanks Dr Allan Goroll (Massachusetts General Hospital/Harvard Medical School) for his mentorship and critical review of this manuscript.

The author has nothing to disclose.

When my grandfather, who speaks limited English, was admitted to a hospital following a stroke amid the coronavirus disease 2019 (COVID-19) pandemic, my family was understandably worried. Sure enough, within just hours of his admission, we were told our normally very calm and beloved Nana was experiencing significant agitation and delirium. He did not understand nurses’ efforts to calm him down, became even more confused, and was eventually sedated and placed in physical restraints. Even though my family’s presence might have prevented some or all of this terrible series of events, the hospital’s visiting policies during the wave of COVID-19 admissions meant that we were forced to wait in the parking lot as they transpired. The hospital’s policy at the time only allowed visitors for pediatrics, end-of-life care, or labor, not for patients with delirium or altered mental status. We were given the option to make a video call, but my grandfather’s stroke had almost completely taken away his vision. Instead of sitting by his side, comforting him, providing explanations in voices he knew and a language he understood, we were left imagining how difficult it must be to suddenly wake up in an unfamiliar environment, with strangers speaking a different language, limited vision, and your arms and legs tied. Intellectually, I understood the hospital’s goals to minimize transmission, but spiritually and emotionally, it felt very cruel and very wrong.

The next day, we successfully petitioned administration to make an exception for one visitor. We argued that our presence would allow for removal of the sedation and restraints. The clinical team agreed that video calls were insufficient in his situation; he was allowed a visitor. We decided that it should be my mother. As soon my grandfather heard her familiar voice, there was a dramatic improvement. He immediately became calmer and restraints were no longer necessary. The team was grateful for a better physical exam and my grandfather was more cooperative with physical therapy. A few days later, unfortunately, the hospital let us know that they had reevaluated their position on my mother’s visits and that she posed an unnecessary COVID-19 risk to medical staff and other patients. And as soon as she left, my grandfather was again agitated and confused for the remaining 3 days of his hospitalization. Although we are grateful that his delirium resolved once he returned home, delirium also has the potential to lead to long-term cognitive impairment.¹

The COVID-19 pandemic has required hospitals around the world to make difficult decisions about how to balance minimizing disease transmission with continuing to provide compassionate and high-quality patient care. Of these many dilemmas, developing flexible visitor policies is particularly difficult. Currently, the Centers for Disease Control and Prevention and many state health departments encourage limiting visitation in general but recognize the need for exceptions in special circumstances such as in end-of-life settings or altered mental status.^2-4

At the hospital level, there is substantial variation in visitation policies among hospitals. Near our family home in San Jose, California, one hospital currently allows visitation for pediatric patients, pregnant patients, end-of-life patients, surgical patients, and patients in the emergency department, as well as those with mental disabilities or safety needs.⁵ A mere 10 minutes away, another hospital has implemented a very different policy that allows only one visitor for pregnant patients and in end-of-life settings; there are no exceptions for patients with cognitive or physical disabilities.⁶ Other hospitals in the United States have gone even further, not permitting visitors even for those at the end of life.⁷ These patients are forced to spend their last few moments alone.

From an infection control perspective, there are certainly valid reasons to limit visitation. Even with temperature screenings, any movement into and out of a hospital poses a risk of transmitting disease. Infected but asymptomatic persons are known to transmit the disease. Additionally, hospitals still treat non–COVID-19 patients who are most susceptible to severe illness should they develop COVID-19 infection. Early in the COVID-19 pandemic, limitations in testing capacity, personal protective equipment (PPE), and staffing made it challenging to ensure safe visitation. In many cases, it was almost impossible to mitigate the transmission risk that visitors posed. Because many hospitals did not have the capacity to test all symptomatic patients, they could not reliably limit visits to COVID-19–positive patients. Additionally, without enough PPE for healthcare workers, hospitals could not afford for visitors to use additional PPE.

Now that testing is more readily available and some aspects of the PPE shortages have been addressed, we should not forget that visitation has significant benefits for both patients’ psychological well-being and their overall outcomes.⁸ Putting aside the emotional support that the physical presence of loved ones can offer, a large body of research indicates that allowing visitors can also meaningfully improve other important patient outcomes. Specifically, the presence of visitors is associated with less fear,⁹ reduced delirium,¹⁰ and even faster recovery.⁸ In many cases, family members can also help improve hospital safety surveillance and catch medical errors.¹¹

I saw firsthand how these benefits are particularly true for visitors who are also a patient’s primary caretaker. When my mother visited my grandfather, she was not simply a visitor but instead served as an active member of the care team. In addition to providing emotional comfort, my mother oriented him to his surroundings, successfully encouraged oral intake, and even caught some medication errors. Particularly for patients with cognitive impairment, caretakers know the patient better than anyone on the clinical team, and their absence can negatively affect the quality of care.

As a family member who also has familiarity with the healthcare system, I share hospitals’ concerns about wanting to minimize disease transmission. I recognize that, even with PPE and screenings, there is still a chance that visitors unknowingly spread COVID-19 to others in the hospital. On a personal level, however, it feels inhumane to maintain this policy even when it affects particularly vulnerable patients like my grandfather. As some hospitals are already doing,¹² we can take steps to allow visitors for such patients while minimizing the likelihood of COVID-19 disease transmission from visitors. Arriving visitors can be screened and required to wear PPE. While these measures may not eliminate the risk of COVID-19 transmission from visitors, they will likely reduce it significantly when implemented properly and make possible a more humane experience for all.¹³

Fortunately, my grandfather is now recovering comfortably at home, surrounded by his loved ones. To this day, however, he has not forgotten what it was like to be confused and alone in the hospital after his stroke. Even with loved ones around, a stroke is a profoundly distressing experience. To go through such an experience alone is even worse. Because of our petitioning, my grandfather was at least allowed a visitor for part of his stay. Other patients are not even allowed that. As we plan for the pandemic’s next waves, hospitals should reevaluate their visitor policies to ensure that their most vulnerable patients do not have to suffer alone.

The author sincerely thanks Dr Allan Goroll (Massachusetts General Hospital/Harvard Medical School) for his mentorship and critical review of this manuscript.

The author has nothing to disclose.

The coronavirus disease of 2019 (COVID-19) pandemic has created innumerable challenges on scales both global and personal while straining health systems and their personnel. Hospitalists and hospital medicine groups are experiencing unique burdens as they confront the pandemic on the frontlines. Hospital medicine groups are being challenged by the rapid operational changes necessary in preparing for and caring for patients with COVID-19. These challenges include drafting new diagnostic and management algorithms, establishing and enacting policies on personal protective equipment (PPE) and patient and provider testing, modifying staffing protocols including deploying staff to new roles or integrating non-hospitalists into hospital medicine roles, and developing capacity for patient surges¹—all in the setting of uncertainty about how the pandemic may affect individual hospitals or health systems and how long these repercussions may last. In this perspective, we describe key lessons we have learned in leading our hospital medicine group during the COVID-19 pandemic: how to apply emotional intelligence to proactively address the emotional effects of the crisis.

In the early days of the COVID-19 pandemic, the evolving knowledge of the disease process, changing national and local public health guidelines, and instability of the PPE supply chain necessitated rapid change. This pace no longer allowed for our typical time frame of weeks to months for implementation of large-scale operational changes; instead, it demanded adaptation in hours to days. We operated under a strategy of developing new workflows and policies that were logical and reflected the best available information at the time.

For instance, our hospital medicine service cared for some of the earliest-identified COVID-19 patients in the United States in early February 2020. Our initial operational plan for caring for patients with COVID-19 involved grouping these patients on a limited number of direct-care hospitalist teams. The advantages of this approach, which benefitted from low numbers of initial patients, were clear: consolidation of clinical and operational knowledge (including optimal PPE practices) in a few individuals, streamlining communication with infectious diseases specialists and public health departments, and requiring change on only a couple of teams while allowing others to continue their usual workflow. However, we soon learned that providers caring for COVID-19 patients were experiencing an onslaught of negative emotions: fear of contracting the virus themselves or carrying it home to infect loved ones, anxiety of not understanding the clinical disease or having treatments to offer, resentment of having been randomly assigned to the team that would care for these patients, and loneliness of being a sole provider experiencing these emotions. We found ourselves in the position of managing these emotional responses reactively.

To reduce the distress experienced by our hospitalists and to lead more effectively, we realized the need to proactively address the emotional effects that the pandemic was having. Several authors who have written about valuable leadership lessons during this time have noted the importance of acknowledging the emotional tolls of such a crisis and creating venues for hospitalists to share their experiences.^1-4 However, solely adding “wellness” as a checklist item for leaders to address fails to capture the nuances of the complex human emotions that hospitalists may endure at this time and how these emotions influence frontline hospitalists’ responses to operational changes. It is critically important for hospital medicine leaders to employ emotional intelligence, defined as “the ability to monitor one’s own and others’ feelings and emotions, to discriminate among them and to use this information to guide one’s thinking and actions.”^5-7 Integrating emotional intelligence allows hospital medicine leaders to anticipate, identify, articulate, and manage the emotional responses to necessary changes and stresses that occur during a crisis such as the COVID-19 pandemic.

As we applied principles of emotional intelligence to our leadership response to the COVID crisis, we found the following seven techniques effective (Appendix Table):

1. ASK. Leaders should ask individual hospitalists “How are you feeling?” instead of “How are you doing?” or “How can I help?” This question may feel too intimate for some, or leaders may worry that the question feels patronizing; however, in our experience, hospitalists respond positively to this prompt, welcome the opportunity to communicate their feelings, and value being heard. Moreover, when hospitalists feel overwhelmed, they may not be able to determine what help they do or do not need. By understanding the emotions of frontline hospitalists, leaders may be better able to address those emotions directly, find solutions to problems, and anticipate reactions to future policies.⁴

2. SHARE. Leaders should model what they ask of frontline hospitalists and share their own feelings, even if they are experiencing mixed or negative emotions. For instance, a leader who is feeling saddened about the death of a patient can begin a meeting by sharing this sentiment. By allowing themselves to display vulnerability, leaders demonstrate courage and promote a culture of openness, honesty, and mutual trust.

3. INITIATE. Leaders should embrace difficult conversations and be transparent about uncertainty, although they may not have the answers and may need to take local responsibility for consequences of decisions made externally, such as those made by the health system or government. Confronting difficult discussions and being transparent about “unknowns” provides acknowledgement, reassurance, and shared experience that expresses to the hospitalist group that, while the future may be unsettled, they will face it together.

4. ANTICIPATE. Leaders should anticipate the emotional responses to operational changes while designing them and rolling them out. While negative emotions may heavily outweigh positive emotions in times of crisis, we have also found that harnessing positive emotions when designing operational initiatives can assist with successful implementation. For example, by surveying our hospitalists, we found that many felt enthusiastic about caring for patients with COVID-19, curious about new skill sets, and passionate about helping in a time of crisis. By generating a list of these hospitalists up front, we were able to preferentially staff COVID-19 teams with providers who were eager to care for those patients and, thereby, minimize anxiety among those who were more apprehensive.

5. ENCOURAGE. Leaders should provide time and space (including virtually) for hospitalists to discuss their emotions.⁸ We found that creating multiple layers of opportunity for expression allows for engagement with a wider range of hospitalists, some of whom may be reluctant to share feelings openly or to a group, whereas others may enjoy the opportunity to reveal their feelings publicly. These varied venues for emotional expression may range from brief individual check-ins to open “office hours” to dedicated meetings such as “Hospitalist Town Halls.” For instance, spending the first few minutes of a meeting with a smaller group by encouraging each participant to share something personal can build community and mutual understanding, as well as cue leaders in to where participants may be on the emotional landscape.

6. NURTURE. Beyond inviting the expression of emotions, leaders should ensure that hospitalists have access to more formal systems of support, especially for hospitalists who may be experiencing more intense negative emotions. Support may be provided through unit- or team-based debriefing sessions, health-system sponsored support programs, or individual counseling sessions.^4,8

7. APPRECIATE. Leaders should deliberately foster gratitude by sincerely and frequently expressing their appreciation. Because expressing gratitude builds resiliency,⁹ cultivating a culture of gratitude may bolster resilience in the entire hospital medicine group. Opportunities for thankfulness abound as hospitalists volunteer for extra shifts, cover for ill colleagues, participate in new working groups and task forces, and sacrifice their personal safety on the front lines. We often incorporate statements of appreciation into one-on-one conversations with hospitalists, during operational and divisional meetings, and in email. We also built gratitude expressions into the daily work on the Respiratory Isolation Unit at our hospital via daily interdisciplinary huddles for frontline providers to share their experiences and emotions. During huddles, providers are asked to pair negative emotions with suggestions for improvement and to share a moment of gratitude. This helps to engender a spirit of camaraderie, shared mission, and collective optimism.

Hospitalists are experiencing a wide range of emotions related to the COVID-19 pandemic. Hospital medicine leaders must have strategies to understand the emotions providers are experiencing. Being aware of and acknowledging these emotions up front can help leaders plan and implement the operational changes necessary to manage the crisis. Because our health system and city have fortunately been spared the worst of the pandemic so far without large volumes of patients with COVID-19, we recognize that the strategies above may be challenging for leaders in overwhelmed health systems. However, we hope that leaders at all levels can apply the lessons we have learned: to ask hospitalists how they are feeling, share their own feelings, initiate difficult conversations when needed, anticipate the emotional effects of operational changes, encourage expressions of emotion in multiple venues, nurture hospitalists who need more formal support, and appreciate frontline hospitalists. While the emotional needs of hospitalists will undoubtedly change over time as the pandemic evolves, we suspect that these strategies will continue to be important over the coming weeks, months, and longer as we settle into the postpandemic world.

The coronavirus disease of 2019 (COVID-19) pandemic has created innumerable challenges on scales both global and personal while straining health systems and their personnel. Hospitalists and hospital medicine groups are experiencing unique burdens as they confront the pandemic on the frontlines. Hospital medicine groups are being challenged by the rapid operational changes necessary in preparing for and caring for patients with COVID-19. These challenges include drafting new diagnostic and management algorithms, establishing and enacting policies on personal protective equipment (PPE) and patient and provider testing, modifying staffing protocols including deploying staff to new roles or integrating non-hospitalists into hospital medicine roles, and developing capacity for patient surges¹—all in the setting of uncertainty about how the pandemic may affect individual hospitals or health systems and how long these repercussions may last. In this perspective, we describe key lessons we have learned in leading our hospital medicine group during the COVID-19 pandemic: how to apply emotional intelligence to proactively address the emotional effects of the crisis.

In the early days of the COVID-19 pandemic, the evolving knowledge of the disease process, changing national and local public health guidelines, and instability of the PPE supply chain necessitated rapid change. This pace no longer allowed for our typical time frame of weeks to months for implementation of large-scale operational changes; instead, it demanded adaptation in hours to days. We operated under a strategy of developing new workflows and policies that were logical and reflected the best available information at the time.

For instance, our hospital medicine service cared for some of the earliest-identified COVID-19 patients in the United States in early February 2020. Our initial operational plan for caring for patients with COVID-19 involved grouping these patients on a limited number of direct-care hospitalist teams. The advantages of this approach, which benefitted from low numbers of initial patients, were clear: consolidation of clinical and operational knowledge (including optimal PPE practices) in a few individuals, streamlining communication with infectious diseases specialists and public health departments, and requiring change on only a couple of teams while allowing others to continue their usual workflow. However, we soon learned that providers caring for COVID-19 patients were experiencing an onslaught of negative emotions: fear of contracting the virus themselves or carrying it home to infect loved ones, anxiety of not understanding the clinical disease or having treatments to offer, resentment of having been randomly assigned to the team that would care for these patients, and loneliness of being a sole provider experiencing these emotions. We found ourselves in the position of managing these emotional responses reactively.

To reduce the distress experienced by our hospitalists and to lead more effectively, we realized the need to proactively address the emotional effects that the pandemic was having. Several authors who have written about valuable leadership lessons during this time have noted the importance of acknowledging the emotional tolls of such a crisis and creating venues for hospitalists to share their experiences.^1-4 However, solely adding “wellness” as a checklist item for leaders to address fails to capture the nuances of the complex human emotions that hospitalists may endure at this time and how these emotions influence frontline hospitalists’ responses to operational changes. It is critically important for hospital medicine leaders to employ emotional intelligence, defined as “the ability to monitor one’s own and others’ feelings and emotions, to discriminate among them and to use this information to guide one’s thinking and actions.”^5-7 Integrating emotional intelligence allows hospital medicine leaders to anticipate, identify, articulate, and manage the emotional responses to necessary changes and stresses that occur during a crisis such as the COVID-19 pandemic.

As we applied principles of emotional intelligence to our leadership response to the COVID crisis, we found the following seven techniques effective (Appendix Table):

1. ASK. Leaders should ask individual hospitalists “How are you feeling?” instead of “How are you doing?” or “How can I help?” This question may feel too intimate for some, or leaders may worry that the question feels patronizing; however, in our experience, hospitalists respond positively to this prompt, welcome the opportunity to communicate their feelings, and value being heard. Moreover, when hospitalists feel overwhelmed, they may not be able to determine what help they do or do not need. By understanding the emotions of frontline hospitalists, leaders may be better able to address those emotions directly, find solutions to problems, and anticipate reactions to future policies.⁴

2. SHARE. Leaders should model what they ask of frontline hospitalists and share their own feelings, even if they are experiencing mixed or negative emotions. For instance, a leader who is feeling saddened about the death of a patient can begin a meeting by sharing this sentiment. By allowing themselves to display vulnerability, leaders demonstrate courage and promote a culture of openness, honesty, and mutual trust.

3. INITIATE. Leaders should embrace difficult conversations and be transparent about uncertainty, although they may not have the answers and may need to take local responsibility for consequences of decisions made externally, such as those made by the health system or government. Confronting difficult discussions and being transparent about “unknowns” provides acknowledgement, reassurance, and shared experience that expresses to the hospitalist group that, while the future may be unsettled, they will face it together.

4. ANTICIPATE. Leaders should anticipate the emotional responses to operational changes while designing them and rolling them out. While negative emotions may heavily outweigh positive emotions in times of crisis, we have also found that harnessing positive emotions when designing operational initiatives can assist with successful implementation. For example, by surveying our hospitalists, we found that many felt enthusiastic about caring for patients with COVID-19, curious about new skill sets, and passionate about helping in a time of crisis. By generating a list of these hospitalists up front, we were able to preferentially staff COVID-19 teams with providers who were eager to care for those patients and, thereby, minimize anxiety among those who were more apprehensive.

5. ENCOURAGE. Leaders should provide time and space (including virtually) for hospitalists to discuss their emotions.⁸ We found that creating multiple layers of opportunity for expression allows for engagement with a wider range of hospitalists, some of whom may be reluctant to share feelings openly or to a group, whereas others may enjoy the opportunity to reveal their feelings publicly. These varied venues for emotional expression may range from brief individual check-ins to open “office hours” to dedicated meetings such as “Hospitalist Town Halls.” For instance, spending the first few minutes of a meeting with a smaller group by encouraging each participant to share something personal can build community and mutual understanding, as well as cue leaders in to where participants may be on the emotional landscape.

6. NURTURE. Beyond inviting the expression of emotions, leaders should ensure that hospitalists have access to more formal systems of support, especially for hospitalists who may be experiencing more intense negative emotions. Support may be provided through unit- or team-based debriefing sessions, health-system sponsored support programs, or individual counseling sessions.^4,8

7. APPRECIATE. Leaders should deliberately foster gratitude by sincerely and frequently expressing their appreciation. Because expressing gratitude builds resiliency,⁹ cultivating a culture of gratitude may bolster resilience in the entire hospital medicine group. Opportunities for thankfulness abound as hospitalists volunteer for extra shifts, cover for ill colleagues, participate in new working groups and task forces, and sacrifice their personal safety on the front lines. We often incorporate statements of appreciation into one-on-one conversations with hospitalists, during operational and divisional meetings, and in email. We also built gratitude expressions into the daily work on the Respiratory Isolation Unit at our hospital via daily interdisciplinary huddles for frontline providers to share their experiences and emotions. During huddles, providers are asked to pair negative emotions with suggestions for improvement and to share a moment of gratitude. This helps to engender a spirit of camaraderie, shared mission, and collective optimism.

Hospitalists are experiencing a wide range of emotions related to the COVID-19 pandemic. Hospital medicine leaders must have strategies to understand the emotions providers are experiencing. Being aware of and acknowledging these emotions up front can help leaders plan and implement the operational changes necessary to manage the crisis. Because our health system and city have fortunately been spared the worst of the pandemic so far without large volumes of patients with COVID-19, we recognize that the strategies above may be challenging for leaders in overwhelmed health systems. However, we hope that leaders at all levels can apply the lessons we have learned: to ask hospitalists how they are feeling, share their own feelings, initiate difficult conversations when needed, anticipate the emotional effects of operational changes, encourage expressions of emotion in multiple venues, nurture hospitalists who need more formal support, and appreciate frontline hospitalists. While the emotional needs of hospitalists will undoubtedly change over time as the pandemic evolves, we suspect that these strategies will continue to be important over the coming weeks, months, and longer as we settle into the postpandemic world.

The coronavirus disease of 2019 (COVID-19) pandemic has created innumerable challenges on scales both global and personal while straining health systems and their personnel. Hospitalists and hospital medicine groups are experiencing unique burdens as they confront the pandemic on the frontlines. Hospital medicine groups are being challenged by the rapid operational changes necessary in preparing for and caring for patients with COVID-19. These challenges include drafting new diagnostic and management algorithms, establishing and enacting policies on personal protective equipment (PPE) and patient and provider testing, modifying staffing protocols including deploying staff to new roles or integrating non-hospitalists into hospital medicine roles, and developing capacity for patient surges¹—all in the setting of uncertainty about how the pandemic may affect individual hospitals or health systems and how long these repercussions may last. In this perspective, we describe key lessons we have learned in leading our hospital medicine group during the COVID-19 pandemic: how to apply emotional intelligence to proactively address the emotional effects of the crisis.

In the early days of the COVID-19 pandemic, the evolving knowledge of the disease process, changing national and local public health guidelines, and instability of the PPE supply chain necessitated rapid change. This pace no longer allowed for our typical time frame of weeks to months for implementation of large-scale operational changes; instead, it demanded adaptation in hours to days. We operated under a strategy of developing new workflows and policies that were logical and reflected the best available information at the time.

For instance, our hospital medicine service cared for some of the earliest-identified COVID-19 patients in the United States in early February 2020. Our initial operational plan for caring for patients with COVID-19 involved grouping these patients on a limited number of direct-care hospitalist teams. The advantages of this approach, which benefitted from low numbers of initial patients, were clear: consolidation of clinical and operational knowledge (including optimal PPE practices) in a few individuals, streamlining communication with infectious diseases specialists and public health departments, and requiring change on only a couple of teams while allowing others to continue their usual workflow. However, we soon learned that providers caring for COVID-19 patients were experiencing an onslaught of negative emotions: fear of contracting the virus themselves or carrying it home to infect loved ones, anxiety of not understanding the clinical disease or having treatments to offer, resentment of having been randomly assigned to the team that would care for these patients, and loneliness of being a sole provider experiencing these emotions. We found ourselves in the position of managing these emotional responses reactively.

To reduce the distress experienced by our hospitalists and to lead more effectively, we realized the need to proactively address the emotional effects that the pandemic was having. Several authors who have written about valuable leadership lessons during this time have noted the importance of acknowledging the emotional tolls of such a crisis and creating venues for hospitalists to share their experiences.^1-4 However, solely adding “wellness” as a checklist item for leaders to address fails to capture the nuances of the complex human emotions that hospitalists may endure at this time and how these emotions influence frontline hospitalists’ responses to operational changes. It is critically important for hospital medicine leaders to employ emotional intelligence, defined as “the ability to monitor one’s own and others’ feelings and emotions, to discriminate among them and to use this information to guide one’s thinking and actions.”^5-7 Integrating emotional intelligence allows hospital medicine leaders to anticipate, identify, articulate, and manage the emotional responses to necessary changes and stresses that occur during a crisis such as the COVID-19 pandemic.

As we applied principles of emotional intelligence to our leadership response to the COVID crisis, we found the following seven techniques effective (Appendix Table):

1. ASK. Leaders should ask individual hospitalists “How are you feeling?” instead of “How are you doing?” or “How can I help?” This question may feel too intimate for some, or leaders may worry that the question feels patronizing; however, in our experience, hospitalists respond positively to this prompt, welcome the opportunity to communicate their feelings, and value being heard. Moreover, when hospitalists feel overwhelmed, they may not be able to determine what help they do or do not need. By understanding the emotions of frontline hospitalists, leaders may be better able to address those emotions directly, find solutions to problems, and anticipate reactions to future policies.⁴

2. SHARE. Leaders should model what they ask of frontline hospitalists and share their own feelings, even if they are experiencing mixed or negative emotions. For instance, a leader who is feeling saddened about the death of a patient can begin a meeting by sharing this sentiment. By allowing themselves to display vulnerability, leaders demonstrate courage and promote a culture of openness, honesty, and mutual trust.

3. INITIATE. Leaders should embrace difficult conversations and be transparent about uncertainty, although they may not have the answers and may need to take local responsibility for consequences of decisions made externally, such as those made by the health system or government. Confronting difficult discussions and being transparent about “unknowns” provides acknowledgement, reassurance, and shared experience that expresses to the hospitalist group that, while the future may be unsettled, they will face it together.

4. ANTICIPATE. Leaders should anticipate the emotional responses to operational changes while designing them and rolling them out. While negative emotions may heavily outweigh positive emotions in times of crisis, we have also found that harnessing positive emotions when designing operational initiatives can assist with successful implementation. For example, by surveying our hospitalists, we found that many felt enthusiastic about caring for patients with COVID-19, curious about new skill sets, and passionate about helping in a time of crisis. By generating a list of these hospitalists up front, we were able to preferentially staff COVID-19 teams with providers who were eager to care for those patients and, thereby, minimize anxiety among those who were more apprehensive.

5. ENCOURAGE. Leaders should provide time and space (including virtually) for hospitalists to discuss their emotions.⁸ We found that creating multiple layers of opportunity for expression allows for engagement with a wider range of hospitalists, some of whom may be reluctant to share feelings openly or to a group, whereas others may enjoy the opportunity to reveal their feelings publicly. These varied venues for emotional expression may range from brief individual check-ins to open “office hours” to dedicated meetings such as “Hospitalist Town Halls.” For instance, spending the first few minutes of a meeting with a smaller group by encouraging each participant to share something personal can build community and mutual understanding, as well as cue leaders in to where participants may be on the emotional landscape.

6. NURTURE. Beyond inviting the expression of emotions, leaders should ensure that hospitalists have access to more formal systems of support, especially for hospitalists who may be experiencing more intense negative emotions. Support may be provided through unit- or team-based debriefing sessions, health-system sponsored support programs, or individual counseling sessions.^4,8

7. APPRECIATE. Leaders should deliberately foster gratitude by sincerely and frequently expressing their appreciation. Because expressing gratitude builds resiliency,⁹ cultivating a culture of gratitude may bolster resilience in the entire hospital medicine group. Opportunities for thankfulness abound as hospitalists volunteer for extra shifts, cover for ill colleagues, participate in new working groups and task forces, and sacrifice their personal safety on the front lines. We often incorporate statements of appreciation into one-on-one conversations with hospitalists, during operational and divisional meetings, and in email. We also built gratitude expressions into the daily work on the Respiratory Isolation Unit at our hospital via daily interdisciplinary huddles for frontline providers to share their experiences and emotions. During huddles, providers are asked to pair negative emotions with suggestions for improvement and to share a moment of gratitude. This helps to engender a spirit of camaraderie, shared mission, and collective optimism.

Hospitalists are experiencing a wide range of emotions related to the COVID-19 pandemic. Hospital medicine leaders must have strategies to understand the emotions providers are experiencing. Being aware of and acknowledging these emotions up front can help leaders plan and implement the operational changes necessary to manage the crisis. Because our health system and city have fortunately been spared the worst of the pandemic so far without large volumes of patients with COVID-19, we recognize that the strategies above may be challenging for leaders in overwhelmed health systems. However, we hope that leaders at all levels can apply the lessons we have learned: to ask hospitalists how they are feeling, share their own feelings, initiate difficult conversations when needed, anticipate the emotional effects of operational changes, encourage expressions of emotion in multiple venues, nurture hospitalists who need more formal support, and appreciate frontline hospitalists. While the emotional needs of hospitalists will undoubtedly change over time as the pandemic evolves, we suspect that these strategies will continue to be important over the coming weeks, months, and longer as we settle into the postpandemic world.

Recent experiences in the transportation industry highlight the importance of getting right the regulation of decision-support systems in high-stakes environments. Two tragic plane crashes resulted in 346 deaths and were deemed, in part, to be related to a cockpit alert system that overwhelmed pilots with multiple notifications.¹ Similarly, a driverless car struck and killed a pedestrian in the street, in part because the car was not programmed to look for humans outside of a crosswalk.² These two bellwether events offer poignant lessons for the healthcare industry in which human lives also depend on decision-support systems.

Clinical decision-support (CDS) systems are computerized applications, often embedded in an electronic health record (EHR), that provide information to clinicians to inform care. Although CDS systems have been used for many years,³ they have never been subjected to any enforcement of formal testing requirements. However, a draft guidance document released in 2019 from the Food and Drug Administration (FDA) outlined new directions for the regulation of CDS systems.⁴ Although the FDA has thus far focused regulatory efforts on predictive systems developed by private manufacturers,^5,6 this new document provides examples of software that would require regulation for CDS systems that hospitals are already using. Thus, this new guidance raises critical questions—will hospitals themselves be evaluated like private manufacturers, be exempted from federal regulation, or require their own specialized regulation? The FDA has not yet clarified its approach to hospitals or hospital-developed CDS systems, which leaves open numerous possibilities in a rapidly evolving regulatory environment.

Although the FDA has officially regulated CDS systems under section 201(h) of the Federal Food, Drug, and Cosmetic Act (1938), only recently has the FDA begun to sketch the shape of its regulatory efforts. This trend to actually regulate CDS systems began with the 21st Century Cures Act (2016) that amended the definition of software systems that qualify as medical devices and outlined criteria under which a system may be exempt from FDA oversight. For example, regulation would not apply to systems that support “population health” or a “healthy lifestyle” or to ones that qualify as “electronic patient records” as long as they do not “interpret or analyze” data within them.⁷ Following the rapid proliferation of many machine learning and other predictive technologies with medical applications, the FDA began the voluntary Digital Health Software Precertification (Pre-Cert) Program in 2017. Through this program, the FDA selected nine companies from more than 100 applicants and certified them across five domains of excellence. Notably, the Pre-Cert Program currently allows for certification of software manufacturers themselves and does not approve or test actual software devices directly. This regulatory pathway will eventually allow manufacturers to apply under a modified premarket review process for individual software as a medical device (SaMD) that use artificial intelligence (AI) and machine learning. In the meantime, however, many hospitals have developed and deployed their own predictive CDS systems that cross the boundaries into the FDA’s purview and, indeed, do “interpret or analyze” data for real-time EHR alerts, population health management, and other applications.

Regulatory oversight for hospitals could provide quality or safety standards where currently there are none. However, such regulations could also interfere with existing local care practices, hinder rapid development of new CDS systems, and may be perceived as interfering in hospital operations. With the current enthusiasm for AI-based technologies and the concurrent lack of evidence to suggest their effectiveness in practice, regulation could also prompt necessary scrutiny of potential harms of CDS systems, an area with even less evidence. At the same time, CDS developers—private or hospital based—may be able to avoid regulation for some devices with well-placed disclaimers about the intended use of the CDS, one of the FDA criteria for determining the degree of oversight. If the FDA were to regulate hospitals or hospital-developed CDS systems, there are several unanswered questions to consider so that such regulations have their intended impact.

First, does the FDA intend to regulate hospitals and hospital-developed software at all? The framework for determining whether a CDS system will be regulated depends on the severity of the clinical scenario, the ability to independently evaluate the model output, and the intended user (Table). Notably, many types of CDS systems that would require regulation under this framework are already commonplace. For example, the FDA intends to regulate software that “identifies patients who may exhibit signs of opioid addiction,” a scenario similar to prediction models already developed at academic hospitals.⁸ The FDA also plans to regulate a software device even if it is not a CDS system if it is “intended to generate an alarm or an alert to notify a caregiver of a life-threatening condition, such as stroke, and the caregiver relies primarily on this alarm or alert to make a treatment decision.” Although there are no published reports of stroke-specific early warning systems in use, analogous nonspecific and sepsis-specific early warning systems to prompt urgent clinical care have been deployed by hospitals directly⁹ and developed for embedding in commercial EHRs.¹⁰ Hospitals need clarification on the FDA’s regulatory intentions for such CDS systems. FDA regulation of hospitals and hospital-developed CDS systems would fill a critical oversight need and potentially strengthen processes to improve safety and effectiveness. But burdensome regulations may also restrain hospitals from tackling complex problems in medicine for which they are uniquely suited.

Such a regulatory environment may be especially prohibitive for safety-net hospitals that could find themselves at a disadvantage in developing their own CDS systems relative to large academic medical centers that are typically endowed with greater resources. Additionally, CDS systems developed at academic medical centers may not generalize well to populations in the community setting, which could further deepen disparities in access to cutting-edge technologies. For example, racial bias in treatment and referral patterns could bias training labels for CDS systems focused on population health management.¹¹ Similarly, the composition of patient skin color in one population may distort predictions of a model in another with a different distribution of skin color, even when the primary outcome of a prediction model is gender.¹² Additional regulatory steps may apply for models that are adapted to new populations or recalibrated across locations and time.¹³ Until there is more data on the clinical impact of such CDS systems, it is unknown how potential differences in evaluation and approval would actually affect clinical outcomes.

Second, would hospitals be eligible for the Pre-Cert program, and if so, would they be held to the same standards as a private technology manufacturer? The domains of excellence required for precertification approval such as “patient safety,” “clinical responsibility,” and “proactive culture” are aligned with the efforts of hospitals that are already overseen and accredited by organizations like the Joint Commission on Accreditation of Healthcare Organizations and the American Nurses Credentialing Center. There is limited motivation for the FDA to be in the business of regulating these aspects of hospital functions. However, while domains like “product quality” and “cybersecurity” may be less familiar to some hospitals, these existing credentialing bodies may be better suited than the FDA to set and enforce standards for hospitals. In contrast, private manufacturers may have deep expertise in these latter domains. Therefore, as with public-private partnerships for the development of predictive radiology applications,¹⁴ synergies between hospitals and manufacturers may also prove useful for obtaining approvals in a competitive marketplace. Simultaneously, such collaborations would continue to raise questions about conflicts of interest and data privacy.

Finally, regardless of how the FDA will regulate hospitals, what will become of predictive CDS systems that fall outside of the FDA’s scope? Hospitals will continue to find themselves in the position of self-regulation without clear guidance. Although the FDA suggests that developers of unregulated CDS systems still follow best practices for software validation and cybersecurity, existing guidance documents in these domains do not cover the full range of concerns relevant to the development, deployment, and oversight of AI-based CDS systems in the clinical domain. Nor do most hospitals have the infrastructure or expertise to oversee their own CDS systems. Disparate recommendations for development, training, and oversight of AI-based medical systems have emerged but have yet to be endorsed by a federal regulatory body or become part of the hospital accreditation process.¹⁵ Optimal local oversight would require a collaboration between clinical experts, hospital operations leaders, statisticians, data scientists, and ethics experts to ensure effectiveness, safety, and fairness.

Hospitals will remain at the forefront of developing and implementing predictive CDS systems. The proposed FDA regulatory framework would mark an important step toward realizing benefit from such systems, but the FDA needs to clarify the requirements for hospitals and hospital-developed CDS systems to ensure reasonable standards that account for their differences from private software manufacturers. Should the FDA choose to focus regulation on private manufacturers only, hospitals leaders may both feel more empowered to develop their own local CDS tools and feel more comfortable buying CDS systems from vendors that have been precertified. This strategy would provide an optimal balance of assurance and flexibility while maintaining quality standards that ultimately improve patient care.

Recent experiences in the transportation industry highlight the importance of getting right the regulation of decision-support systems in high-stakes environments. Two tragic plane crashes resulted in 346 deaths and were deemed, in part, to be related to a cockpit alert system that overwhelmed pilots with multiple notifications.¹ Similarly, a driverless car struck and killed a pedestrian in the street, in part because the car was not programmed to look for humans outside of a crosswalk.² These two bellwether events offer poignant lessons for the healthcare industry in which human lives also depend on decision-support systems.

Clinical decision-support (CDS) systems are computerized applications, often embedded in an electronic health record (EHR), that provide information to clinicians to inform care. Although CDS systems have been used for many years,³ they have never been subjected to any enforcement of formal testing requirements. However, a draft guidance document released in 2019 from the Food and Drug Administration (FDA) outlined new directions for the regulation of CDS systems.⁴ Although the FDA has thus far focused regulatory efforts on predictive systems developed by private manufacturers,^5,6 this new document provides examples of software that would require regulation for CDS systems that hospitals are already using. Thus, this new guidance raises critical questions—will hospitals themselves be evaluated like private manufacturers, be exempted from federal regulation, or require their own specialized regulation? The FDA has not yet clarified its approach to hospitals or hospital-developed CDS systems, which leaves open numerous possibilities in a rapidly evolving regulatory environment.

Although the FDA has officially regulated CDS systems under section 201(h) of the Federal Food, Drug, and Cosmetic Act (1938), only recently has the FDA begun to sketch the shape of its regulatory efforts. This trend to actually regulate CDS systems began with the 21st Century Cures Act (2016) that amended the definition of software systems that qualify as medical devices and outlined criteria under which a system may be exempt from FDA oversight. For example, regulation would not apply to systems that support “population health” or a “healthy lifestyle” or to ones that qualify as “electronic patient records” as long as they do not “interpret or analyze” data within them.⁷ Following the rapid proliferation of many machine learning and other predictive technologies with medical applications, the FDA began the voluntary Digital Health Software Precertification (Pre-Cert) Program in 2017. Through this program, the FDA selected nine companies from more than 100 applicants and certified them across five domains of excellence. Notably, the Pre-Cert Program currently allows for certification of software manufacturers themselves and does not approve or test actual software devices directly. This regulatory pathway will eventually allow manufacturers to apply under a modified premarket review process for individual software as a medical device (SaMD) that use artificial intelligence (AI) and machine learning. In the meantime, however, many hospitals have developed and deployed their own predictive CDS systems that cross the boundaries into the FDA’s purview and, indeed, do “interpret or analyze” data for real-time EHR alerts, population health management, and other applications.

Regulatory oversight for hospitals could provide quality or safety standards where currently there are none. However, such regulations could also interfere with existing local care practices, hinder rapid development of new CDS systems, and may be perceived as interfering in hospital operations. With the current enthusiasm for AI-based technologies and the concurrent lack of evidence to suggest their effectiveness in practice, regulation could also prompt necessary scrutiny of potential harms of CDS systems, an area with even less evidence. At the same time, CDS developers—private or hospital based—may be able to avoid regulation for some devices with well-placed disclaimers about the intended use of the CDS, one of the FDA criteria for determining the degree of oversight. If the FDA were to regulate hospitals or hospital-developed CDS systems, there are several unanswered questions to consider so that such regulations have their intended impact.

First, does the FDA intend to regulate hospitals and hospital-developed software at all? The framework for determining whether a CDS system will be regulated depends on the severity of the clinical scenario, the ability to independently evaluate the model output, and the intended user (Table). Notably, many types of CDS systems that would require regulation under this framework are already commonplace. For example, the FDA intends to regulate software that “identifies patients who may exhibit signs of opioid addiction,” a scenario similar to prediction models already developed at academic hospitals.⁸ The FDA also plans to regulate a software device even if it is not a CDS system if it is “intended to generate an alarm or an alert to notify a caregiver of a life-threatening condition, such as stroke, and the caregiver relies primarily on this alarm or alert to make a treatment decision.” Although there are no published reports of stroke-specific early warning systems in use, analogous nonspecific and sepsis-specific early warning systems to prompt urgent clinical care have been deployed by hospitals directly⁹ and developed for embedding in commercial EHRs.¹⁰ Hospitals need clarification on the FDA’s regulatory intentions for such CDS systems. FDA regulation of hospitals and hospital-developed CDS systems would fill a critical oversight need and potentially strengthen processes to improve safety and effectiveness. But burdensome regulations may also restrain hospitals from tackling complex problems in medicine for which they are uniquely suited.

Such a regulatory environment may be especially prohibitive for safety-net hospitals that could find themselves at a disadvantage in developing their own CDS systems relative to large academic medical centers that are typically endowed with greater resources. Additionally, CDS systems developed at academic medical centers may not generalize well to populations in the community setting, which could further deepen disparities in access to cutting-edge technologies. For example, racial bias in treatment and referral patterns could bias training labels for CDS systems focused on population health management.¹¹ Similarly, the composition of patient skin color in one population may distort predictions of a model in another with a different distribution of skin color, even when the primary outcome of a prediction model is gender.¹² Additional regulatory steps may apply for models that are adapted to new populations or recalibrated across locations and time.¹³ Until there is more data on the clinical impact of such CDS systems, it is unknown how potential differences in evaluation and approval would actually affect clinical outcomes.

Second, would hospitals be eligible for the Pre-Cert program, and if so, would they be held to the same standards as a private technology manufacturer? The domains of excellence required for precertification approval such as “patient safety,” “clinical responsibility,” and “proactive culture” are aligned with the efforts of hospitals that are already overseen and accredited by organizations like the Joint Commission on Accreditation of Healthcare Organizations and the American Nurses Credentialing Center. There is limited motivation for the FDA to be in the business of regulating these aspects of hospital functions. However, while domains like “product quality” and “cybersecurity” may be less familiar to some hospitals, these existing credentialing bodies may be better suited than the FDA to set and enforce standards for hospitals. In contrast, private manufacturers may have deep expertise in these latter domains. Therefore, as with public-private partnerships for the development of predictive radiology applications,¹⁴ synergies between hospitals and manufacturers may also prove useful for obtaining approvals in a competitive marketplace. Simultaneously, such collaborations would continue to raise questions about conflicts of interest and data privacy.

Finally, regardless of how the FDA will regulate hospitals, what will become of predictive CDS systems that fall outside of the FDA’s scope? Hospitals will continue to find themselves in the position of self-regulation without clear guidance. Although the FDA suggests that developers of unregulated CDS systems still follow best practices for software validation and cybersecurity, existing guidance documents in these domains do not cover the full range of concerns relevant to the development, deployment, and oversight of AI-based CDS systems in the clinical domain. Nor do most hospitals have the infrastructure or expertise to oversee their own CDS systems. Disparate recommendations for development, training, and oversight of AI-based medical systems have emerged but have yet to be endorsed by a federal regulatory body or become part of the hospital accreditation process.¹⁵ Optimal local oversight would require a collaboration between clinical experts, hospital operations leaders, statisticians, data scientists, and ethics experts to ensure effectiveness, safety, and fairness.

Hospitals will remain at the forefront of developing and implementing predictive CDS systems. The proposed FDA regulatory framework would mark an important step toward realizing benefit from such systems, but the FDA needs to clarify the requirements for hospitals and hospital-developed CDS systems to ensure reasonable standards that account for their differences from private software manufacturers. Should the FDA choose to focus regulation on private manufacturers only, hospitals leaders may both feel more empowered to develop their own local CDS tools and feel more comfortable buying CDS systems from vendors that have been precertified. This strategy would provide an optimal balance of assurance and flexibility while maintaining quality standards that ultimately improve patient care.

Recent experiences in the transportation industry highlight the importance of getting right the regulation of decision-support systems in high-stakes environments. Two tragic plane crashes resulted in 346 deaths and were deemed, in part, to be related to a cockpit alert system that overwhelmed pilots with multiple notifications.¹ Similarly, a driverless car struck and killed a pedestrian in the street, in part because the car was not programmed to look for humans outside of a crosswalk.² These two bellwether events offer poignant lessons for the healthcare industry in which human lives also depend on decision-support systems.

Clinical decision-support (CDS) systems are computerized applications, often embedded in an electronic health record (EHR), that provide information to clinicians to inform care. Although CDS systems have been used for many years,³ they have never been subjected to any enforcement of formal testing requirements. However, a draft guidance document released in 2019 from the Food and Drug Administration (FDA) outlined new directions for the regulation of CDS systems.⁴ Although the FDA has thus far focused regulatory efforts on predictive systems developed by private manufacturers,^5,6 this new document provides examples of software that would require regulation for CDS systems that hospitals are already using. Thus, this new guidance raises critical questions—will hospitals themselves be evaluated like private manufacturers, be exempted from federal regulation, or require their own specialized regulation? The FDA has not yet clarified its approach to hospitals or hospital-developed CDS systems, which leaves open numerous possibilities in a rapidly evolving regulatory environment.

Although the FDA has officially regulated CDS systems under section 201(h) of the Federal Food, Drug, and Cosmetic Act (1938), only recently has the FDA begun to sketch the shape of its regulatory efforts. This trend to actually regulate CDS systems began with the 21st Century Cures Act (2016) that amended the definition of software systems that qualify as medical devices and outlined criteria under which a system may be exempt from FDA oversight. For example, regulation would not apply to systems that support “population health” or a “healthy lifestyle” or to ones that qualify as “electronic patient records” as long as they do not “interpret or analyze” data within them.⁷ Following the rapid proliferation of many machine learning and other predictive technologies with medical applications, the FDA began the voluntary Digital Health Software Precertification (Pre-Cert) Program in 2017. Through this program, the FDA selected nine companies from more than 100 applicants and certified them across five domains of excellence. Notably, the Pre-Cert Program currently allows for certification of software manufacturers themselves and does not approve or test actual software devices directly. This regulatory pathway will eventually allow manufacturers to apply under a modified premarket review process for individual software as a medical device (SaMD) that use artificial intelligence (AI) and machine learning. In the meantime, however, many hospitals have developed and deployed their own predictive CDS systems that cross the boundaries into the FDA’s purview and, indeed, do “interpret or analyze” data for real-time EHR alerts, population health management, and other applications.

Regulatory oversight for hospitals could provide quality or safety standards where currently there are none. However, such regulations could also interfere with existing local care practices, hinder rapid development of new CDS systems, and may be perceived as interfering in hospital operations. With the current enthusiasm for AI-based technologies and the concurrent lack of evidence to suggest their effectiveness in practice, regulation could also prompt necessary scrutiny of potential harms of CDS systems, an area with even less evidence. At the same time, CDS developers—private or hospital based—may be able to avoid regulation for some devices with well-placed disclaimers about the intended use of the CDS, one of the FDA criteria for determining the degree of oversight. If the FDA were to regulate hospitals or hospital-developed CDS systems, there are several unanswered questions to consider so that such regulations have their intended impact.

First, does the FDA intend to regulate hospitals and hospital-developed software at all? The framework for determining whether a CDS system will be regulated depends on the severity of the clinical scenario, the ability to independently evaluate the model output, and the intended user (Table). Notably, many types of CDS systems that would require regulation under this framework are already commonplace. For example, the FDA intends to regulate software that “identifies patients who may exhibit signs of opioid addiction,” a scenario similar to prediction models already developed at academic hospitals.⁸ The FDA also plans to regulate a software device even if it is not a CDS system if it is “intended to generate an alarm or an alert to notify a caregiver of a life-threatening condition, such as stroke, and the caregiver relies primarily on this alarm or alert to make a treatment decision.” Although there are no published reports of stroke-specific early warning systems in use, analogous nonspecific and sepsis-specific early warning systems to prompt urgent clinical care have been deployed by hospitals directly⁹ and developed for embedding in commercial EHRs.¹⁰ Hospitals need clarification on the FDA’s regulatory intentions for such CDS systems. FDA regulation of hospitals and hospital-developed CDS systems would fill a critical oversight need and potentially strengthen processes to improve safety and effectiveness. But burdensome regulations may also restrain hospitals from tackling complex problems in medicine for which they are uniquely suited.

Such a regulatory environment may be especially prohibitive for safety-net hospitals that could find themselves at a disadvantage in developing their own CDS systems relative to large academic medical centers that are typically endowed with greater resources. Additionally, CDS systems developed at academic medical centers may not generalize well to populations in the community setting, which could further deepen disparities in access to cutting-edge technologies. For example, racial bias in treatment and referral patterns could bias training labels for CDS systems focused on population health management.¹¹ Similarly, the composition of patient skin color in one population may distort predictions of a model in another with a different distribution of skin color, even when the primary outcome of a prediction model is gender.¹² Additional regulatory steps may apply for models that are adapted to new populations or recalibrated across locations and time.¹³ Until there is more data on the clinical impact of such CDS systems, it is unknown how potential differences in evaluation and approval would actually affect clinical outcomes.

Second, would hospitals be eligible for the Pre-Cert program, and if so, would they be held to the same standards as a private technology manufacturer? The domains of excellence required for precertification approval such as “patient safety,” “clinical responsibility,” and “proactive culture” are aligned with the efforts of hospitals that are already overseen and accredited by organizations like the Joint Commission on Accreditation of Healthcare Organizations and the American Nurses Credentialing Center. There is limited motivation for the FDA to be in the business of regulating these aspects of hospital functions. However, while domains like “product quality” and “cybersecurity” may be less familiar to some hospitals, these existing credentialing bodies may be better suited than the FDA to set and enforce standards for hospitals. In contrast, private manufacturers may have deep expertise in these latter domains. Therefore, as with public-private partnerships for the development of predictive radiology applications,¹⁴ synergies between hospitals and manufacturers may also prove useful for obtaining approvals in a competitive marketplace. Simultaneously, such collaborations would continue to raise questions about conflicts of interest and data privacy.

Finally, regardless of how the FDA will regulate hospitals, what will become of predictive CDS systems that fall outside of the FDA’s scope? Hospitals will continue to find themselves in the position of self-regulation without clear guidance. Although the FDA suggests that developers of unregulated CDS systems still follow best practices for software validation and cybersecurity, existing guidance documents in these domains do not cover the full range of concerns relevant to the development, deployment, and oversight of AI-based CDS systems in the clinical domain. Nor do most hospitals have the infrastructure or expertise to oversee their own CDS systems. Disparate recommendations for development, training, and oversight of AI-based medical systems have emerged but have yet to be endorsed by a federal regulatory body or become part of the hospital accreditation process.¹⁵ Optimal local oversight would require a collaboration between clinical experts, hospital operations leaders, statisticians, data scientists, and ethics experts to ensure effectiveness, safety, and fairness.

Hospitals will remain at the forefront of developing and implementing predictive CDS systems. The proposed FDA regulatory framework would mark an important step toward realizing benefit from such systems, but the FDA needs to clarify the requirements for hospitals and hospital-developed CDS systems to ensure reasonable standards that account for their differences from private software manufacturers. Should the FDA choose to focus regulation on private manufacturers only, hospitals leaders may both feel more empowered to develop their own local CDS tools and feel more comfortable buying CDS systems from vendors that have been precertified. This strategy would provide an optimal balance of assurance and flexibility while maintaining quality standards that ultimately improve patient care.

There is growing momentum to hold drug manufacturers accountable for the more than 400,000 US opioid overdose deaths that have occurred since 1999.¹ As state lawsuits against pharmaceutical manufacturers and distributors wind their way through the legal system, hospitals—which may benefit from settlement funds—have been paying close attention. Recently, former Governor John Kasich (R-Ohio), West Virginia University president E. Gordon Gee, and America’s Essential Hospitals argued that adequately compensating hospitals for the costs of being on the crisis’ “front lines” requires prioritizing them as settlement fund recipients.²

Hospitals should be laying the groundwork for how settlement funds might be used. They may consider enhancing some of the most promising, evidence-based services for individuals with opioid use disorders (OUDs), including improving treatment for commonly associated health conditions such as HIV and hepatitis C virus (HCV); expanding ambulatory long-term antibiotic treatment for endocarditis and other intravenous drug use–associated infections; more broadly adopting harm-reduction practices such as naloxone coprescribing; and applying best practices to caring for substance-exposed infants. They could also develop clinical services not already provided, including creating programs for OUD management during pregnancy and initiating medication for OUD in inpatient, emergency department, and ambulatory settings. In short, hospitals play a critical role in engaging people with OUD in treatment at every possible opportunity.³

When considering how to most effectively use opioid settlement funding, hospitals may consider adding or expanding these much-needed clinical services to address opioid-­related harms; however, their efforts should not stop there. Investments made outside hospital walls could have a significant effect on the public’s health, especially if they target social determinants of health. By tackling factors in the pathway to developing OUD, such as lack of meaningful employment, affordable housing, and mental health care, hospitals can move beyond treating the downstream consequences of addiction and toward preventing community-level opioid-related harms. To accomplish this daunting goal, hospitals will need to strengthen existing relationships with community partners and build new ones. Yet in a 2015 study, only 54% of nonprofit hospitals proposed a strategy to address the overdose crisis that involved community partnering.⁴

In this Perspective, we describe the following three strategies hospitals can use to multiply the reach of their opioid settlement funding by addressing root causes of opioid use through primary prevention: (1) supporting economic opportunities in their communities, (2) expanding affordable housing options in surrounding neighborhoods, and (3) building capacity in ambulatory practices and pharmacies to prevent OUD (Table).

Lack of economic opportunity is one of many root causes of opioid use. For example, a recent study found that automotive assembly plant closures were associated with increases in opioid overdose mortality.⁵ To tackle this complex issue, hospitals can play a crucial role in expanding employment and career advancement options for members of their local communities. Specifically, hospitals can do the following:

• Create jobs within the healthcare system and preferentially recruit and hire from surrounding neighborhoods
• Establish structured career development programs to build skills among entry-level healthcare employees
• Award contracts of varying sizes to locally owned businesses
• Employ individuals with lived experience with substance use disorders, such as peer recovery coaches⁶

To illustrate how health systems are investing in enhancing career opportunities for members of their communities, hundreds of institutions have implemented “School at Work,” a 6-month career development program for entry-level healthcare employees.⁷ The hospitals’ Human Resources department trains participants in communication skills, reading and writing, patient safety and satisfaction, medical terminology, and strategies for success and career advancement. Evaluations of this program have demonstrated improved employee outcomes and a favorable return on investment for hospitals.⁸

As “anchor institutions” and large employers in many communities, hospitals can simultaneously enhance their own workforce and offer employment opportunities that can help break the cycle of addiction that commonly traps individuals and families in communities affected by the overdose crisis.

Hospitals are increasingly supporting interventions that fall outside their traditional purview as they seek to improve population health, such as developing safe green outdoor spaces and increasing access to healthy food options by supporting local farmers markets and grocers.⁹ Stable, decent, and affordable housing is critically important to health and well-being,¹⁰ and there is a well-documented association of opioid use disorder and opioid misuse with housing instability.¹¹ Given evidence of improved outcomes with hospital-led housing interventions,¹² a growing number of hospitals are partnering with housing authorities and community groups to help do the following¹³:

• Contribute to supportive housing options
• Provide environmental health assessments, repairs, and renovations
• Buy or develop affordable housing units

Boston Medical Center, where one in four inpatients are experiencing homelessnes and one in three pediatric emergency department patients are housing insecure, provides an example of how a hospital has invested in housing.¹⁴ In 2017, the hospital began a 5-year, $6.5 million investment in community partnerships in surrounding neighborhoods. Instead of building housing units or acting as a landlord, the hospital chose to invest funding in creative ways to increase the pool of affordable housing. It invested $1 million to rehabilitate permanent, supportive housing units for individuals with mental health conditions in a nearby Boston neighborhood and in a housing stabilization program for people with complex medical issues including substance use disorder. It provided resources to a homeless shelter near the hospital and to the Boston Health Care for the Homeless Program, which provides healthcare to individuals with housing instability. It also funded a community wellness advocate based at the hospital, who received training in substance use disorders and served as a liaison between the hospital and the Boston Housing Authority.

Housing instability is just one of the social determinants of health that hospitals have the capacity to address as they consider where to invest their opioid settlement funds.

Finally, hospitals can partner with community ambulatory practices and pharmacies to prevent the progression to problematic opioid use and OUD. Specifically, hospitals can do as follows:

• Provide evidence-based training to community providers on safe prescribing practices for acute and chronic pain management, as well as postoperative, postprocedural, and postpartum pain management
• Support ambulatory providers in expanding office-based mental health treatment through direct care via telemedicine and in building mental health treatment capacity through consultation, continuing medical education, and telementorship (eg, Project ECHO¹⁵)
• Support ambulatory providers to implement risk reduction strategies to prevent initiation of problematic opioid use, particularly among adolescents and young adults
• Partner with local pharmacies to promote point-of-­prescription counseling on the risks and benefits of opioids

Hospitals bring key strengths and resources to these prevention-­oriented partnerships. First, they may have resources available for clinical research, implementation support, program evaluation, and quality improvement, bringing such expertise to partnerships with ambulatory practices and pharmacies. They likely have specific expertise among their staff, including areas such as pain management, obstetric care, pediatrics, and adolescent medicine, and can provide specialists for consultation services or telementoring initiatives. They also can organize continuing medical education and can offer in-service training at local practices and pharmacies.

Project ECHO is one example of telementoring to build capacity among community providers to manage chronic pain and address addiction and other related harms.¹⁶ The Project ECHO model includes virtual sessions with didactic content and case presentations during which specialists mentor community clinicians. Specific to primary prevention, telementoring has been shown to improve access to evidence-based treatment of chronic pain and mental health conditions,^17,18 which could prevent the development of OUD. By equipping community clinicians with tools to prevent the development of problematic opioid use, hospitals can help reduce the downstream burden of OUD and its associated morbidity, mortality, and costs.

The opioid crisis has devastated families, reduced life expectancy in certain communities,¹⁹ and had a substantial financial impact on hospitals—resulting in an estimated $11 billion in costs to US hospitals each year.²⁰ This ongoing crisis is only going to be compounded by the recent emergence of the SARS-CoV-2 virus. Hospital resources are being strained in unprecedented ways, which has required unprecedented responses in order to continue to serve their communities. Supporting economic opportunity, stable housing, and mental health treatment will be challenging in this new environment but has never been more urgently needed. If opioid settlement funds are targeted to US hospitals, they should be held accountable for where funds are spent because they have a unique opportunity to focus on primary prevention in their communities—confronting OUD before it begins.²¹ However, if hospitals use opioid settlement funding only to continue to provide services already offered, or fail to make bold investments in their communities, this public health crisis will continue to strain the resources of those providing clinical care on the front lines.

The authors wish to thank Hilary Peterson of the RAND Corporation for preparing the paper for submission. She was not compensated for her contribution.

The authors report being supported by grants from the National Institute on Drug Abuse of the National Institutes of Health under awards R21DA045212 (Dr Faherty), K23DA045085 (Dr Hadland), L40DA042434 (Dr Hadland), K23DA038720 (Dr Patrick), R01DA045729 (Dr Patrick), and P50DA046351 (Dr Stein). Dr Hadland also reports grant support from the Thrasher Research Fund and the Academic Pediatric Association. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

There is growing momentum to hold drug manufacturers accountable for the more than 400,000 US opioid overdose deaths that have occurred since 1999.¹ As state lawsuits against pharmaceutical manufacturers and distributors wind their way through the legal system, hospitals—which may benefit from settlement funds—have been paying close attention. Recently, former Governor John Kasich (R-Ohio), West Virginia University president E. Gordon Gee, and America’s Essential Hospitals argued that adequately compensating hospitals for the costs of being on the crisis’ “front lines” requires prioritizing them as settlement fund recipients.²

Hospitals should be laying the groundwork for how settlement funds might be used. They may consider enhancing some of the most promising, evidence-based services for individuals with opioid use disorders (OUDs), including improving treatment for commonly associated health conditions such as HIV and hepatitis C virus (HCV); expanding ambulatory long-term antibiotic treatment for endocarditis and other intravenous drug use–associated infections; more broadly adopting harm-reduction practices such as naloxone coprescribing; and applying best practices to caring for substance-exposed infants. They could also develop clinical services not already provided, including creating programs for OUD management during pregnancy and initiating medication for OUD in inpatient, emergency department, and ambulatory settings. In short, hospitals play a critical role in engaging people with OUD in treatment at every possible opportunity.³

When considering how to most effectively use opioid settlement funding, hospitals may consider adding or expanding these much-needed clinical services to address opioid-­related harms; however, their efforts should not stop there. Investments made outside hospital walls could have a significant effect on the public’s health, especially if they target social determinants of health. By tackling factors in the pathway to developing OUD, such as lack of meaningful employment, affordable housing, and mental health care, hospitals can move beyond treating the downstream consequences of addiction and toward preventing community-level opioid-related harms. To accomplish this daunting goal, hospitals will need to strengthen existing relationships with community partners and build new ones. Yet in a 2015 study, only 54% of nonprofit hospitals proposed a strategy to address the overdose crisis that involved community partnering.⁴

In this Perspective, we describe the following three strategies hospitals can use to multiply the reach of their opioid settlement funding by addressing root causes of opioid use through primary prevention: (1) supporting economic opportunities in their communities, (2) expanding affordable housing options in surrounding neighborhoods, and (3) building capacity in ambulatory practices and pharmacies to prevent OUD (Table).

Lack of economic opportunity is one of many root causes of opioid use. For example, a recent study found that automotive assembly plant closures were associated with increases in opioid overdose mortality.⁵ To tackle this complex issue, hospitals can play a crucial role in expanding employment and career advancement options for members of their local communities. Specifically, hospitals can do the following:

• Create jobs within the healthcare system and preferentially recruit and hire from surrounding neighborhoods
• Establish structured career development programs to build skills among entry-level healthcare employees
• Award contracts of varying sizes to locally owned businesses
• Employ individuals with lived experience with substance use disorders, such as peer recovery coaches⁶

To illustrate how health systems are investing in enhancing career opportunities for members of their communities, hundreds of institutions have implemented “School at Work,” a 6-month career development program for entry-level healthcare employees.⁷ The hospitals’ Human Resources department trains participants in communication skills, reading and writing, patient safety and satisfaction, medical terminology, and strategies for success and career advancement. Evaluations of this program have demonstrated improved employee outcomes and a favorable return on investment for hospitals.⁸

As “anchor institutions” and large employers in many communities, hospitals can simultaneously enhance their own workforce and offer employment opportunities that can help break the cycle of addiction that commonly traps individuals and families in communities affected by the overdose crisis.

Hospitals are increasingly supporting interventions that fall outside their traditional purview as they seek to improve population health, such as developing safe green outdoor spaces and increasing access to healthy food options by supporting local farmers markets and grocers.⁹ Stable, decent, and affordable housing is critically important to health and well-being,¹⁰ and there is a well-documented association of opioid use disorder and opioid misuse with housing instability.¹¹ Given evidence of improved outcomes with hospital-led housing interventions,¹² a growing number of hospitals are partnering with housing authorities and community groups to help do the following¹³:

• Contribute to supportive housing options
• Provide environmental health assessments, repairs, and renovations
• Buy or develop affordable housing units

Boston Medical Center, where one in four inpatients are experiencing homelessnes and one in three pediatric emergency department patients are housing insecure, provides an example of how a hospital has invested in housing.¹⁴ In 2017, the hospital began a 5-year, $6.5 million investment in community partnerships in surrounding neighborhoods. Instead of building housing units or acting as a landlord, the hospital chose to invest funding in creative ways to increase the pool of affordable housing. It invested $1 million to rehabilitate permanent, supportive housing units for individuals with mental health conditions in a nearby Boston neighborhood and in a housing stabilization program for people with complex medical issues including substance use disorder. It provided resources to a homeless shelter near the hospital and to the Boston Health Care for the Homeless Program, which provides healthcare to individuals with housing instability. It also funded a community wellness advocate based at the hospital, who received training in substance use disorders and served as a liaison between the hospital and the Boston Housing Authority.

Housing instability is just one of the social determinants of health that hospitals have the capacity to address as they consider where to invest their opioid settlement funds.

Finally, hospitals can partner with community ambulatory practices and pharmacies to prevent the progression to problematic opioid use and OUD. Specifically, hospitals can do as follows:

• Provide evidence-based training to community providers on safe prescribing practices for acute and chronic pain management, as well as postoperative, postprocedural, and postpartum pain management
• Support ambulatory providers in expanding office-based mental health treatment through direct care via telemedicine and in building mental health treatment capacity through consultation, continuing medical education, and telementorship (eg, Project ECHO¹⁵)
• Support ambulatory providers to implement risk reduction strategies to prevent initiation of problematic opioid use, particularly among adolescents and young adults
• Partner with local pharmacies to promote point-of-­prescription counseling on the risks and benefits of opioids

Hospitals bring key strengths and resources to these prevention-­oriented partnerships. First, they may have resources available for clinical research, implementation support, program evaluation, and quality improvement, bringing such expertise to partnerships with ambulatory practices and pharmacies. They likely have specific expertise among their staff, including areas such as pain management, obstetric care, pediatrics, and adolescent medicine, and can provide specialists for consultation services or telementoring initiatives. They also can organize continuing medical education and can offer in-service training at local practices and pharmacies.

Project ECHO is one example of telementoring to build capacity among community providers to manage chronic pain and address addiction and other related harms.¹⁶ The Project ECHO model includes virtual sessions with didactic content and case presentations during which specialists mentor community clinicians. Specific to primary prevention, telementoring has been shown to improve access to evidence-based treatment of chronic pain and mental health conditions,^17,18 which could prevent the development of OUD. By equipping community clinicians with tools to prevent the development of problematic opioid use, hospitals can help reduce the downstream burden of OUD and its associated morbidity, mortality, and costs.

The opioid crisis has devastated families, reduced life expectancy in certain communities,¹⁹ and had a substantial financial impact on hospitals—resulting in an estimated $11 billion in costs to US hospitals each year.²⁰ This ongoing crisis is only going to be compounded by the recent emergence of the SARS-CoV-2 virus. Hospital resources are being strained in unprecedented ways, which has required unprecedented responses in order to continue to serve their communities. Supporting economic opportunity, stable housing, and mental health treatment will be challenging in this new environment but has never been more urgently needed. If opioid settlement funds are targeted to US hospitals, they should be held accountable for where funds are spent because they have a unique opportunity to focus on primary prevention in their communities—confronting OUD before it begins.²¹ However, if hospitals use opioid settlement funding only to continue to provide services already offered, or fail to make bold investments in their communities, this public health crisis will continue to strain the resources of those providing clinical care on the front lines.

The authors wish to thank Hilary Peterson of the RAND Corporation for preparing the paper for submission. She was not compensated for her contribution.

The authors report being supported by grants from the National Institute on Drug Abuse of the National Institutes of Health under awards R21DA045212 (Dr Faherty), K23DA045085 (Dr Hadland), L40DA042434 (Dr Hadland), K23DA038720 (Dr Patrick), R01DA045729 (Dr Patrick), and P50DA046351 (Dr Stein). Dr Hadland also reports grant support from the Thrasher Research Fund and the Academic Pediatric Association. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

There is growing momentum to hold drug manufacturers accountable for the more than 400,000 US opioid overdose deaths that have occurred since 1999.¹ As state lawsuits against pharmaceutical manufacturers and distributors wind their way through the legal system, hospitals—which may benefit from settlement funds—have been paying close attention. Recently, former Governor John Kasich (R-Ohio), West Virginia University president E. Gordon Gee, and America’s Essential Hospitals argued that adequately compensating hospitals for the costs of being on the crisis’ “front lines” requires prioritizing them as settlement fund recipients.²

Hospitals should be laying the groundwork for how settlement funds might be used. They may consider enhancing some of the most promising, evidence-based services for individuals with opioid use disorders (OUDs), including improving treatment for commonly associated health conditions such as HIV and hepatitis C virus (HCV); expanding ambulatory long-term antibiotic treatment for endocarditis and other intravenous drug use–associated infections; more broadly adopting harm-reduction practices such as naloxone coprescribing; and applying best practices to caring for substance-exposed infants. They could also develop clinical services not already provided, including creating programs for OUD management during pregnancy and initiating medication for OUD in inpatient, emergency department, and ambulatory settings. In short, hospitals play a critical role in engaging people with OUD in treatment at every possible opportunity.³

When considering how to most effectively use opioid settlement funding, hospitals may consider adding or expanding these much-needed clinical services to address opioid-­related harms; however, their efforts should not stop there. Investments made outside hospital walls could have a significant effect on the public’s health, especially if they target social determinants of health. By tackling factors in the pathway to developing OUD, such as lack of meaningful employment, affordable housing, and mental health care, hospitals can move beyond treating the downstream consequences of addiction and toward preventing community-level opioid-related harms. To accomplish this daunting goal, hospitals will need to strengthen existing relationships with community partners and build new ones. Yet in a 2015 study, only 54% of nonprofit hospitals proposed a strategy to address the overdose crisis that involved community partnering.⁴

In this Perspective, we describe the following three strategies hospitals can use to multiply the reach of their opioid settlement funding by addressing root causes of opioid use through primary prevention: (1) supporting economic opportunities in their communities, (2) expanding affordable housing options in surrounding neighborhoods, and (3) building capacity in ambulatory practices and pharmacies to prevent OUD (Table).

Lack of economic opportunity is one of many root causes of opioid use. For example, a recent study found that automotive assembly plant closures were associated with increases in opioid overdose mortality.⁵ To tackle this complex issue, hospitals can play a crucial role in expanding employment and career advancement options for members of their local communities. Specifically, hospitals can do the following:

• Create jobs within the healthcare system and preferentially recruit and hire from surrounding neighborhoods
• Establish structured career development programs to build skills among entry-level healthcare employees
• Award contracts of varying sizes to locally owned businesses
• Employ individuals with lived experience with substance use disorders, such as peer recovery coaches⁶

To illustrate how health systems are investing in enhancing career opportunities for members of their communities, hundreds of institutions have implemented “School at Work,” a 6-month career development program for entry-level healthcare employees.⁷ The hospitals’ Human Resources department trains participants in communication skills, reading and writing, patient safety and satisfaction, medical terminology, and strategies for success and career advancement. Evaluations of this program have demonstrated improved employee outcomes and a favorable return on investment for hospitals.⁸

As “anchor institutions” and large employers in many communities, hospitals can simultaneously enhance their own workforce and offer employment opportunities that can help break the cycle of addiction that commonly traps individuals and families in communities affected by the overdose crisis.

Hospitals are increasingly supporting interventions that fall outside their traditional purview as they seek to improve population health, such as developing safe green outdoor spaces and increasing access to healthy food options by supporting local farmers markets and grocers.⁹ Stable, decent, and affordable housing is critically important to health and well-being,¹⁰ and there is a well-documented association of opioid use disorder and opioid misuse with housing instability.¹¹ Given evidence of improved outcomes with hospital-led housing interventions,¹² a growing number of hospitals are partnering with housing authorities and community groups to help do the following¹³:

• Contribute to supportive housing options
• Provide environmental health assessments, repairs, and renovations
• Buy or develop affordable housing units

Boston Medical Center, where one in four inpatients are experiencing homelessnes and one in three pediatric emergency department patients are housing insecure, provides an example of how a hospital has invested in housing.¹⁴ In 2017, the hospital began a 5-year, $6.5 million investment in community partnerships in surrounding neighborhoods. Instead of building housing units or acting as a landlord, the hospital chose to invest funding in creative ways to increase the pool of affordable housing. It invested $1 million to rehabilitate permanent, supportive housing units for individuals with mental health conditions in a nearby Boston neighborhood and in a housing stabilization program for people with complex medical issues including substance use disorder. It provided resources to a homeless shelter near the hospital and to the Boston Health Care for the Homeless Program, which provides healthcare to individuals with housing instability. It also funded a community wellness advocate based at the hospital, who received training in substance use disorders and served as a liaison between the hospital and the Boston Housing Authority.

Housing instability is just one of the social determinants of health that hospitals have the capacity to address as they consider where to invest their opioid settlement funds.

Finally, hospitals can partner with community ambulatory practices and pharmacies to prevent the progression to problematic opioid use and OUD. Specifically, hospitals can do as follows:

• Provide evidence-based training to community providers on safe prescribing practices for acute and chronic pain management, as well as postoperative, postprocedural, and postpartum pain management
• Support ambulatory providers in expanding office-based mental health treatment through direct care via telemedicine and in building mental health treatment capacity through consultation, continuing medical education, and telementorship (eg, Project ECHO¹⁵)
• Support ambulatory providers to implement risk reduction strategies to prevent initiation of problematic opioid use, particularly among adolescents and young adults
• Partner with local pharmacies to promote point-of-­prescription counseling on the risks and benefits of opioids

Hospitals bring key strengths and resources to these prevention-­oriented partnerships. First, they may have resources available for clinical research, implementation support, program evaluation, and quality improvement, bringing such expertise to partnerships with ambulatory practices and pharmacies. They likely have specific expertise among their staff, including areas such as pain management, obstetric care, pediatrics, and adolescent medicine, and can provide specialists for consultation services or telementoring initiatives. They also can organize continuing medical education and can offer in-service training at local practices and pharmacies.

Project ECHO is one example of telementoring to build capacity among community providers to manage chronic pain and address addiction and other related harms.¹⁶ The Project ECHO model includes virtual sessions with didactic content and case presentations during which specialists mentor community clinicians. Specific to primary prevention, telementoring has been shown to improve access to evidence-based treatment of chronic pain and mental health conditions,^17,18 which could prevent the development of OUD. By equipping community clinicians with tools to prevent the development of problematic opioid use, hospitals can help reduce the downstream burden of OUD and its associated morbidity, mortality, and costs.

The opioid crisis has devastated families, reduced life expectancy in certain communities,¹⁹ and had a substantial financial impact on hospitals—resulting in an estimated $11 billion in costs to US hospitals each year.²⁰ This ongoing crisis is only going to be compounded by the recent emergence of the SARS-CoV-2 virus. Hospital resources are being strained in unprecedented ways, which has required unprecedented responses in order to continue to serve their communities. Supporting economic opportunity, stable housing, and mental health treatment will be challenging in this new environment but has never been more urgently needed. If opioid settlement funds are targeted to US hospitals, they should be held accountable for where funds are spent because they have a unique opportunity to focus on primary prevention in their communities—confronting OUD before it begins.²¹ However, if hospitals use opioid settlement funding only to continue to provide services already offered, or fail to make bold investments in their communities, this public health crisis will continue to strain the resources of those providing clinical care on the front lines.

The authors wish to thank Hilary Peterson of the RAND Corporation for preparing the paper for submission. She was not compensated for her contribution.

The authors report being supported by grants from the National Institute on Drug Abuse of the National Institutes of Health under awards R21DA045212 (Dr Faherty), K23DA045085 (Dr Hadland), L40DA042434 (Dr Hadland), K23DA038720 (Dr Patrick), R01DA045729 (Dr Patrick), and P50DA046351 (Dr Stein). Dr Hadland also reports grant support from the Thrasher Research Fund and the Academic Pediatric Association. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The 1918 H1N1 influenza pandemic was the most severe pandemic in recent history. Fifty to 100 million individuals died worldwide, with approximately 675,000 deaths in the United States.^1-3 The fatality rate was approximately 2% and was highest during the second and third waves of the disease.⁴ At that time, there were no diagnostic tests for influenza infection, influenza vaccines, antiviral drugs, antibiotics to treat secondary bacterial infections, or mechanical ventilation. Some cities decided to close schools, limit public gatherings, self-isolate, and issue quarantine orders; the federal government took no central role.

The 1918 influenza pandemic seems far away in history, but my mother often tells me stories about her own grandmother who disliked shaking anyone’s hands and would worry when people coughed or sneezed around her. It sounded like she was overreacting. Now, we can better relate to her concerns. Life has changed dramatically.

In mid-February 2020, news spread that the coronavirus disease 2019 (COVID-19) had spread from Wuhan, China, to a number of countries in Asia and the Middle East. I was following the news with great sadness for those affected countries, especially for Iran, my country of origin, which had become an epicenter of COVID-19. We were not worried for ourselves in the United States. These infections seemed far away. However, once Italy became the new epicenter of COVID-19 with alarmingly high death rates, I grasped the inevitable reality: The novel coronavirus would not spare the United States and would not spare New York.

Then the virus arrived in New York City. On March 10, 2020, our hospital recommended using teledermatology instead of in-person visits in an attempt to keep patients safe in their own homes. Cases of COVID-19 were escalating, hospitals were filling up, health care workers were falling ill, and there was a shortage of health care staff and personal protective equipment (PPE). Dermatologists at various hospitals were asked to retrain to help care for COVID-19 patients.

On March 13, flights from Europe to the United States were suspended. A statewide stay-at-home order subsequently went into effect on March 22. It felt surreal. From March 23 on, various specialty physicians and nurses in our hospital volunteered to work as frontline staff in the newly prepared annex where patients with possible COVID-19 would arrive. My dermatology co-residents and I started working as frontline physicians. Everything we had heard from the countries affected first had become our reality. Our hospital, part of the largest public health care system in the nation, became a dedicated COVID-19 treatment center.

Large numbers of scared patients with symptoms of COVID-19 flooded the annex. We sent the majority of them home, unable to offer them even a diagnostic test, and advised them to stay isolated. We only had the capacity to test those who required hospital admission.

It broke my heart even more when my colleagues became patients. We often felt helpless, not being able to help every patient and not being able to help our infected colleagues.

Elective surgeries were suspended. Inpatient beds, including specialized intensive care unit beds, rapidly filled up with COVID-19 patients. To help with the surge of patients, our hospital added medical and intensive care unit beds. The hospital became surreal, the corridors eerily empty and silent while every bed was filled, and health care workers were rushing around the inpatient units.

Life quickly became filled with fears—worries about how sick the patients would be, how much we would be able to help them, whether we would have enough PPE, who among our friends or family might be infected next, and whether we might ourselves be next. As PPE became scarce, I desperately searched for some form of protective equipment. I hunted for protective masks, face shields, eye protection, and gowns. We had to reuse disposable N95 masks and face shields multiple times and disinfect them as best we could. Our attendings ordered any protective gear they could find for us. Nearly everything was sold out; the very few items remaining would not for arrive for months. I could have never imagined that I would be afraid of going to work, of not having the appropriate protective gear, and that any day might be my last because of my profession.

New York City had become the epicenter of COVID-19. The city, the country, and the world were in chaos. Hospitals were overflowing, and makeshift morgues were appearing outside of hospitals. Those who could fled the city. Despite warnings from experts, we were not prepared. The number of deaths was climbing rapidly. There was no clarity on who could be tested or how to get it done. It felt like a nightmare.

Social distancing was in place, nonessential businesses were shut down, street vendors disappeared, and people were advised to wear face coverings. People were afraid of each other, afraid of getting too close and catching the virus. New York City—The City That Never Sleeps—went into deep sleep. Every day brought ever greater numbers of infected patients and more deaths.

Every day at 7:00 pm, people in New York City started clapping from their windows to salute health care workers, bringing tears to my eyes—tears for the gratitude of people mixed with tears of fear for my life and the lives of my patients and colleagues. I made arrangements for the event of falling ill, including a list of names and contact details of my family and close friends so they could be reached in case I ended up in intensive care or died.

After around 2 months of lockdown, New York City passed its peak, and the epicenter moved on. The current death toll (ie, confirmed deaths due to COVID-19) in New York stands at 18,836, while the reported death toll in the United States is 143,868, according to the Centers for Disease Control and Prevention. New York City has started a phased reopening to a new normal. Elective care has resumed, and people are leaving their homes again, eager to bring some sense of normalcy back into their lives.

I fear for those who will contract the virus in the next wave. I wonder what we will have learned.

Acknowledgment
The author wishes to thank Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina), for his friendship and invaluable assistance with the conception and editing of this manuscript.

The 1918 H1N1 influenza pandemic was the most severe pandemic in recent history. Fifty to 100 million individuals died worldwide, with approximately 675,000 deaths in the United States.^1-3 The fatality rate was approximately 2% and was highest during the second and third waves of the disease.⁴ At that time, there were no diagnostic tests for influenza infection, influenza vaccines, antiviral drugs, antibiotics to treat secondary bacterial infections, or mechanical ventilation. Some cities decided to close schools, limit public gatherings, self-isolate, and issue quarantine orders; the federal government took no central role.

The 1918 influenza pandemic seems far away in history, but my mother often tells me stories about her own grandmother who disliked shaking anyone’s hands and would worry when people coughed or sneezed around her. It sounded like she was overreacting. Now, we can better relate to her concerns. Life has changed dramatically.

In mid-February 2020, news spread that the coronavirus disease 2019 (COVID-19) had spread from Wuhan, China, to a number of countries in Asia and the Middle East. I was following the news with great sadness for those affected countries, especially for Iran, my country of origin, which had become an epicenter of COVID-19. We were not worried for ourselves in the United States. These infections seemed far away. However, once Italy became the new epicenter of COVID-19 with alarmingly high death rates, I grasped the inevitable reality: The novel coronavirus would not spare the United States and would not spare New York.

Then the virus arrived in New York City. On March 10, 2020, our hospital recommended using teledermatology instead of in-person visits in an attempt to keep patients safe in their own homes. Cases of COVID-19 were escalating, hospitals were filling up, health care workers were falling ill, and there was a shortage of health care staff and personal protective equipment (PPE). Dermatologists at various hospitals were asked to retrain to help care for COVID-19 patients.

On March 13, flights from Europe to the United States were suspended. A statewide stay-at-home order subsequently went into effect on March 22. It felt surreal. From March 23 on, various specialty physicians and nurses in our hospital volunteered to work as frontline staff in the newly prepared annex where patients with possible COVID-19 would arrive. My dermatology co-residents and I started working as frontline physicians. Everything we had heard from the countries affected first had become our reality. Our hospital, part of the largest public health care system in the nation, became a dedicated COVID-19 treatment center.

Large numbers of scared patients with symptoms of COVID-19 flooded the annex. We sent the majority of them home, unable to offer them even a diagnostic test, and advised them to stay isolated. We only had the capacity to test those who required hospital admission.

It broke my heart even more when my colleagues became patients. We often felt helpless, not being able to help every patient and not being able to help our infected colleagues.

Elective surgeries were suspended. Inpatient beds, including specialized intensive care unit beds, rapidly filled up with COVID-19 patients. To help with the surge of patients, our hospital added medical and intensive care unit beds. The hospital became surreal, the corridors eerily empty and silent while every bed was filled, and health care workers were rushing around the inpatient units.

Life quickly became filled with fears—worries about how sick the patients would be, how much we would be able to help them, whether we would have enough PPE, who among our friends or family might be infected next, and whether we might ourselves be next. As PPE became scarce, I desperately searched for some form of protective equipment. I hunted for protective masks, face shields, eye protection, and gowns. We had to reuse disposable N95 masks and face shields multiple times and disinfect them as best we could. Our attendings ordered any protective gear they could find for us. Nearly everything was sold out; the very few items remaining would not for arrive for months. I could have never imagined that I would be afraid of going to work, of not having the appropriate protective gear, and that any day might be my last because of my profession.

New York City had become the epicenter of COVID-19. The city, the country, and the world were in chaos. Hospitals were overflowing, and makeshift morgues were appearing outside of hospitals. Those who could fled the city. Despite warnings from experts, we were not prepared. The number of deaths was climbing rapidly. There was no clarity on who could be tested or how to get it done. It felt like a nightmare.

Social distancing was in place, nonessential businesses were shut down, street vendors disappeared, and people were advised to wear face coverings. People were afraid of each other, afraid of getting too close and catching the virus. New York City—The City That Never Sleeps—went into deep sleep. Every day brought ever greater numbers of infected patients and more deaths.

Every day at 7:00 pm, people in New York City started clapping from their windows to salute health care workers, bringing tears to my eyes—tears for the gratitude of people mixed with tears of fear for my life and the lives of my patients and colleagues. I made arrangements for the event of falling ill, including a list of names and contact details of my family and close friends so they could be reached in case I ended up in intensive care or died.

After around 2 months of lockdown, New York City passed its peak, and the epicenter moved on. The current death toll (ie, confirmed deaths due to COVID-19) in New York stands at 18,836, while the reported death toll in the United States is 143,868, according to the Centers for Disease Control and Prevention. New York City has started a phased reopening to a new normal. Elective care has resumed, and people are leaving their homes again, eager to bring some sense of normalcy back into their lives.

I fear for those who will contract the virus in the next wave. I wonder what we will have learned.

Acknowledgment
The author wishes to thank Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina), for his friendship and invaluable assistance with the conception and editing of this manuscript.

The 1918 H1N1 influenza pandemic was the most severe pandemic in recent history. Fifty to 100 million individuals died worldwide, with approximately 675,000 deaths in the United States.^1-3 The fatality rate was approximately 2% and was highest during the second and third waves of the disease.⁴ At that time, there were no diagnostic tests for influenza infection, influenza vaccines, antiviral drugs, antibiotics to treat secondary bacterial infections, or mechanical ventilation. Some cities decided to close schools, limit public gatherings, self-isolate, and issue quarantine orders; the federal government took no central role.

The 1918 influenza pandemic seems far away in history, but my mother often tells me stories about her own grandmother who disliked shaking anyone’s hands and would worry when people coughed or sneezed around her. It sounded like she was overreacting. Now, we can better relate to her concerns. Life has changed dramatically.

In mid-February 2020, news spread that the coronavirus disease 2019 (COVID-19) had spread from Wuhan, China, to a number of countries in Asia and the Middle East. I was following the news with great sadness for those affected countries, especially for Iran, my country of origin, which had become an epicenter of COVID-19. We were not worried for ourselves in the United States. These infections seemed far away. However, once Italy became the new epicenter of COVID-19 with alarmingly high death rates, I grasped the inevitable reality: The novel coronavirus would not spare the United States and would not spare New York.

Then the virus arrived in New York City. On March 10, 2020, our hospital recommended using teledermatology instead of in-person visits in an attempt to keep patients safe in their own homes. Cases of COVID-19 were escalating, hospitals were filling up, health care workers were falling ill, and there was a shortage of health care staff and personal protective equipment (PPE). Dermatologists at various hospitals were asked to retrain to help care for COVID-19 patients.

On March 13, flights from Europe to the United States were suspended. A statewide stay-at-home order subsequently went into effect on March 22. It felt surreal. From March 23 on, various specialty physicians and nurses in our hospital volunteered to work as frontline staff in the newly prepared annex where patients with possible COVID-19 would arrive. My dermatology co-residents and I started working as frontline physicians. Everything we had heard from the countries affected first had become our reality. Our hospital, part of the largest public health care system in the nation, became a dedicated COVID-19 treatment center.

Large numbers of scared patients with symptoms of COVID-19 flooded the annex. We sent the majority of them home, unable to offer them even a diagnostic test, and advised them to stay isolated. We only had the capacity to test those who required hospital admission.

It broke my heart even more when my colleagues became patients. We often felt helpless, not being able to help every patient and not being able to help our infected colleagues.

Elective surgeries were suspended. Inpatient beds, including specialized intensive care unit beds, rapidly filled up with COVID-19 patients. To help with the surge of patients, our hospital added medical and intensive care unit beds. The hospital became surreal, the corridors eerily empty and silent while every bed was filled, and health care workers were rushing around the inpatient units.

Life quickly became filled with fears—worries about how sick the patients would be, how much we would be able to help them, whether we would have enough PPE, who among our friends or family might be infected next, and whether we might ourselves be next. As PPE became scarce, I desperately searched for some form of protective equipment. I hunted for protective masks, face shields, eye protection, and gowns. We had to reuse disposable N95 masks and face shields multiple times and disinfect them as best we could. Our attendings ordered any protective gear they could find for us. Nearly everything was sold out; the very few items remaining would not for arrive for months. I could have never imagined that I would be afraid of going to work, of not having the appropriate protective gear, and that any day might be my last because of my profession.

New York City had become the epicenter of COVID-19. The city, the country, and the world were in chaos. Hospitals were overflowing, and makeshift morgues were appearing outside of hospitals. Those who could fled the city. Despite warnings from experts, we were not prepared. The number of deaths was climbing rapidly. There was no clarity on who could be tested or how to get it done. It felt like a nightmare.

Social distancing was in place, nonessential businesses were shut down, street vendors disappeared, and people were advised to wear face coverings. People were afraid of each other, afraid of getting too close and catching the virus. New York City—The City That Never Sleeps—went into deep sleep. Every day brought ever greater numbers of infected patients and more deaths.

Every day at 7:00 pm, people in New York City started clapping from their windows to salute health care workers, bringing tears to my eyes—tears for the gratitude of people mixed with tears of fear for my life and the lives of my patients and colleagues. I made arrangements for the event of falling ill, including a list of names and contact details of my family and close friends so they could be reached in case I ended up in intensive care or died.

After around 2 months of lockdown, New York City passed its peak, and the epicenter moved on. The current death toll (ie, confirmed deaths due to COVID-19) in New York stands at 18,836, while the reported death toll in the United States is 143,868, according to the Centers for Disease Control and Prevention. New York City has started a phased reopening to a new normal. Elective care has resumed, and people are leaving their homes again, eager to bring some sense of normalcy back into their lives.

I fear for those who will contract the virus in the next wave. I wonder what we will have learned.

Acknowledgment
The author wishes to thank Steven R. Feldman, MD, PhD (Winston-Salem, North Carolina), for his friendship and invaluable assistance with the conception and editing of this manuscript.

Early testing for actionable genomic alterations is now recommended for metastatic pancreatic cancer patients who progress on therapy or experience intolerable toxicity and who are potential candidates for additional treatment after first-line therapy, according to an American Society of Clinical Oncology guideline update.

Both germline and somatic testing, including for microsatellite instability/mismatch repair deficiency, BRCA mutations with known significance, and NTRK gene fusions, are recommended in this population, reported Davendra P.S. Sohal, MD, MPH, of the University of Cincinnati, and colleagues on ASCO’s expert panel. The update was published online Aug. 5 in the Journal of Clinical Oncology.

The ASCO guideline on clinical decision making for patients with metastatic pancreatic cancer was first published in 2016 to address initial assessment and first- and second-line treatment options, supportive care, and follow-up and was updated in 2018. The current update is based on new evidence of benefit with targeted therapy options after first-line therapy or as maintenance therapy.

The phase 3 POLO trial, for example, showed significantly improved progression-free survival with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for maintenance therapy after first-line treatment in patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer that had not progressed during first-line platinum-based chemotherapy. An integrated analysis of three studies showed that entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, safely induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumors, and a phase 1-2 study showed that the highly selective TRK inhibitor larotrectinib had marked and durable antitumor activity in both children and adults with TRK fusion-positive solid tumors.

With respect to the new recommendation endorsing early testing for actionable genomic alterations (Recommendation 1.5), the authors noted that the results of testing can lead to treatment with PARP inhibitors, programmed death-1 (PD-1) checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies.

“Genomic testing is recommended as part of an initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy,” the new recommendation states.

A “qualifying statement” further notes that the decision to test should “involve a discussion between the patient and physician regarding the frequency of actionable findings, treatment implications of testing results, and genetic counseling related to germline testing.”

Recommendation 1.5 is rated by the panel as “strong” and is based on informal consensus.

The panel also added two recommendations on treatment options after first-line therapy:

• Recommendation 3.1 calls for treatment with larotrectinib or entrectinib in patient with tumors harboring NTRK fusions.
• Recommendation 3.3 states that patients with a germline BRCA1 or BCA2 mutation who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks can receive chemotherapy or PARP inhibition with olaparib.

The relevant evidence for these two recommendations is of low quality, but shows that the benefits outweigh the harms; the strength of both recommendations is “moderate.”

A qualifying statement for the latter notes that “the decision to continue treatment with chemotherapy or proceed to maintenance therapy with olaparib should be based on a discussion between the patient and the oncologist, including consideration of whether a maximum response and plateau in response to chemotherapy have been achieved, the level of cumulative toxicities associated with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost, and clinical evidence, including a lack of overall survival benefit demonstrated in the POLO randomized controlled trial.”

This focused update includes minor modifications to three existing recommendations:

• In addition to capecitabine or erlotinib, nab-paclitaxel is now included in Recommendation 2.3 as another possible add-on to gemcitabine alone for patients with either an Eastern Cooperative Oncology Group (ECOG) performance score of 2 or a comorbidity profile that precludes more aggressive regimens. The recommendation was also updated to encourage proactive dose and schedule adjustments to minimize toxicities.
• Recommendation 3.5 now includes patients treated previously with a gemcitabine-based regimen in the criteria for the preferred second-line treatment combination of fluorouracil plus nanoliposomal irinotecan or fluorouracil plus irinotecan “where the former is unavailable.”
• Recommendation 3.7 now includes nab-paclitaxel as an add-on option to gemcitabine, and nanoliposomal irinotecan as an add-on option to fluorouracil for second-line therapy – with proactive dose and schedule adjustments to minimize toxicities – in patients with ECOG performance score of 2 or a comorbidity profile that precludes more aggressive regimens.

These three minor modifications reflect new evidence in the first-line treatment setting, including from the FRAGRANCE trial, and are based on expert panel consensus. All other recommendations in the 2018 update are endorsed for the current update, which is available at the ASCO website.

Dr. Sohal reported honoraria from Foundation Medicine, and consulting or advisory roles with Perthera, Ability Pharma, and PierianDx. He reported research funding to his institution from Novartis, Celgene, OncoMed, Bayer, Genentech, Bristol Myers Squibb, Agios, Incyte, Loxo, and Rafael Pharmaceuticals.

[email protected]

SOURCE: Sohal D et al. J Clin Oncol. 2020 Aug 5. doi: 10.1200/JCO.20.01364.

Early testing for actionable genomic alterations is now recommended for metastatic pancreatic cancer patients who progress on therapy or experience intolerable toxicity and who are potential candidates for additional treatment after first-line therapy, according to an American Society of Clinical Oncology guideline update.

Both germline and somatic testing, including for microsatellite instability/mismatch repair deficiency, BRCA mutations with known significance, and NTRK gene fusions, are recommended in this population, reported Davendra P.S. Sohal, MD, MPH, of the University of Cincinnati, and colleagues on ASCO’s expert panel. The update was published online Aug. 5 in the Journal of Clinical Oncology.

The ASCO guideline on clinical decision making for patients with metastatic pancreatic cancer was first published in 2016 to address initial assessment and first- and second-line treatment options, supportive care, and follow-up and was updated in 2018. The current update is based on new evidence of benefit with targeted therapy options after first-line therapy or as maintenance therapy.

The phase 3 POLO trial, for example, showed significantly improved progression-free survival with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for maintenance therapy after first-line treatment in patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer that had not progressed during first-line platinum-based chemotherapy. An integrated analysis of three studies showed that entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, safely induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumors, and a phase 1-2 study showed that the highly selective TRK inhibitor larotrectinib had marked and durable antitumor activity in both children and adults with TRK fusion-positive solid tumors.

With respect to the new recommendation endorsing early testing for actionable genomic alterations (Recommendation 1.5), the authors noted that the results of testing can lead to treatment with PARP inhibitors, programmed death-1 (PD-1) checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies.

“Genomic testing is recommended as part of an initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy,” the new recommendation states.

A “qualifying statement” further notes that the decision to test should “involve a discussion between the patient and physician regarding the frequency of actionable findings, treatment implications of testing results, and genetic counseling related to germline testing.”

Recommendation 1.5 is rated by the panel as “strong” and is based on informal consensus.

The panel also added two recommendations on treatment options after first-line therapy:

• Recommendation 3.1 calls for treatment with larotrectinib or entrectinib in patient with tumors harboring NTRK fusions.
• Recommendation 3.3 states that patients with a germline BRCA1 or BCA2 mutation who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks can receive chemotherapy or PARP inhibition with olaparib.

The relevant evidence for these two recommendations is of low quality, but shows that the benefits outweigh the harms; the strength of both recommendations is “moderate.”

A qualifying statement for the latter notes that “the decision to continue treatment with chemotherapy or proceed to maintenance therapy with olaparib should be based on a discussion between the patient and the oncologist, including consideration of whether a maximum response and plateau in response to chemotherapy have been achieved, the level of cumulative toxicities associated with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost, and clinical evidence, including a lack of overall survival benefit demonstrated in the POLO randomized controlled trial.”

This focused update includes minor modifications to three existing recommendations:

• In addition to capecitabine or erlotinib, nab-paclitaxel is now included in Recommendation 2.3 as another possible add-on to gemcitabine alone for patients with either an Eastern Cooperative Oncology Group (ECOG) performance score of 2 or a comorbidity profile that precludes more aggressive regimens. The recommendation was also updated to encourage proactive dose and schedule adjustments to minimize toxicities.
• Recommendation 3.5 now includes patients treated previously with a gemcitabine-based regimen in the criteria for the preferred second-line treatment combination of fluorouracil plus nanoliposomal irinotecan or fluorouracil plus irinotecan “where the former is unavailable.”
• Recommendation 3.7 now includes nab-paclitaxel as an add-on option to gemcitabine, and nanoliposomal irinotecan as an add-on option to fluorouracil for second-line therapy – with proactive dose and schedule adjustments to minimize toxicities – in patients with ECOG performance score of 2 or a comorbidity profile that precludes more aggressive regimens.

These three minor modifications reflect new evidence in the first-line treatment setting, including from the FRAGRANCE trial, and are based on expert panel consensus. All other recommendations in the 2018 update are endorsed for the current update, which is available at the ASCO website.

Dr. Sohal reported honoraria from Foundation Medicine, and consulting or advisory roles with Perthera, Ability Pharma, and PierianDx. He reported research funding to his institution from Novartis, Celgene, OncoMed, Bayer, Genentech, Bristol Myers Squibb, Agios, Incyte, Loxo, and Rafael Pharmaceuticals.

[email protected]

SOURCE: Sohal D et al. J Clin Oncol. 2020 Aug 5. doi: 10.1200/JCO.20.01364.

Early testing for actionable genomic alterations is now recommended for metastatic pancreatic cancer patients who progress on therapy or experience intolerable toxicity and who are potential candidates for additional treatment after first-line therapy, according to an American Society of Clinical Oncology guideline update.

Both germline and somatic testing, including for microsatellite instability/mismatch repair deficiency, BRCA mutations with known significance, and NTRK gene fusions, are recommended in this population, reported Davendra P.S. Sohal, MD, MPH, of the University of Cincinnati, and colleagues on ASCO’s expert panel. The update was published online Aug. 5 in the Journal of Clinical Oncology.

The ASCO guideline on clinical decision making for patients with metastatic pancreatic cancer was first published in 2016 to address initial assessment and first- and second-line treatment options, supportive care, and follow-up and was updated in 2018. The current update is based on new evidence of benefit with targeted therapy options after first-line therapy or as maintenance therapy.

The phase 3 POLO trial, for example, showed significantly improved progression-free survival with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for maintenance therapy after first-line treatment in patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer that had not progressed during first-line platinum-based chemotherapy. An integrated analysis of three studies showed that entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, safely induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumors, and a phase 1-2 study showed that the highly selective TRK inhibitor larotrectinib had marked and durable antitumor activity in both children and adults with TRK fusion-positive solid tumors.

With respect to the new recommendation endorsing early testing for actionable genomic alterations (Recommendation 1.5), the authors noted that the results of testing can lead to treatment with PARP inhibitors, programmed death-1 (PD-1) checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies.

“Genomic testing is recommended as part of an initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy,” the new recommendation states.

A “qualifying statement” further notes that the decision to test should “involve a discussion between the patient and physician regarding the frequency of actionable findings, treatment implications of testing results, and genetic counseling related to germline testing.”

Recommendation 1.5 is rated by the panel as “strong” and is based on informal consensus.

The panel also added two recommendations on treatment options after first-line therapy:

• Recommendation 3.1 calls for treatment with larotrectinib or entrectinib in patient with tumors harboring NTRK fusions.
• Recommendation 3.3 states that patients with a germline BRCA1 or BCA2 mutation who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks can receive chemotherapy or PARP inhibition with olaparib.

The relevant evidence for these two recommendations is of low quality, but shows that the benefits outweigh the harms; the strength of both recommendations is “moderate.”

A qualifying statement for the latter notes that “the decision to continue treatment with chemotherapy or proceed to maintenance therapy with olaparib should be based on a discussion between the patient and the oncologist, including consideration of whether a maximum response and plateau in response to chemotherapy have been achieved, the level of cumulative toxicities associated with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost, and clinical evidence, including a lack of overall survival benefit demonstrated in the POLO randomized controlled trial.”

This focused update includes minor modifications to three existing recommendations:

• In addition to capecitabine or erlotinib, nab-paclitaxel is now included in Recommendation 2.3 as another possible add-on to gemcitabine alone for patients with either an Eastern Cooperative Oncology Group (ECOG) performance score of 2 or a comorbidity profile that precludes more aggressive regimens. The recommendation was also updated to encourage proactive dose and schedule adjustments to minimize toxicities.
• Recommendation 3.5 now includes patients treated previously with a gemcitabine-based regimen in the criteria for the preferred second-line treatment combination of fluorouracil plus nanoliposomal irinotecan or fluorouracil plus irinotecan “where the former is unavailable.”
• Recommendation 3.7 now includes nab-paclitaxel as an add-on option to gemcitabine, and nanoliposomal irinotecan as an add-on option to fluorouracil for second-line therapy – with proactive dose and schedule adjustments to minimize toxicities – in patients with ECOG performance score of 2 or a comorbidity profile that precludes more aggressive regimens.

These three minor modifications reflect new evidence in the first-line treatment setting, including from the FRAGRANCE trial, and are based on expert panel consensus. All other recommendations in the 2018 update are endorsed for the current update, which is available at the ASCO website.

Dr. Sohal reported honoraria from Foundation Medicine, and consulting or advisory roles with Perthera, Ability Pharma, and PierianDx. He reported research funding to his institution from Novartis, Celgene, OncoMed, Bayer, Genentech, Bristol Myers Squibb, Agios, Incyte, Loxo, and Rafael Pharmaceuticals.

[email protected]

SOURCE: Sohal D et al. J Clin Oncol. 2020 Aug 5. doi: 10.1200/JCO.20.01364.

Second lung cancers occurring up to a decade after the first are on the rise, but their prognosis is similar – especially when detected early – which supports long-term surveillance in survivors, finds a large population-based study.

Although guidelines recommend continued annual low-dose CT scan surveillance extending beyond 4 years for this population based on expert consensus, long-term evidence of benefit is lacking.

Investigators led by John M. Varlotto, MD, a radiation oncologist at the University of Massachusetts Medical Center, Worcester, analyzed Surveillance, Epidemiology & End Results (SEER) data for more than 58,000 patients with first and sometimes second non–small cell lung cancers initially treated by surgical resection.

Study results reported in Lung Cancer showed that the age-adjusted incidence of second lung cancers occurring 4-10 years after the first lung cancer rose sharply during the 1985-2014 study period, driven by a large uptick in women patients.

Among all patients, second lung cancers had similar overall survival as first lung cancers, but poorer lung cancer–specific survival. However, among the subset of patients having early-stage resectable disease (tumors measuring less than 4 cm with negative nodes), both outcomes were statistically indistinguishable.

“Because our investigation noted that the overall survival of patients undergoing a second lung cancer operation was similar to those patients undergoing a first operation, and because there is a rising rate of second lung cancer in lung cancer survivors, we feel that continued surveillance beyond the 4-year interval as recommended by the American Association for Thoracic Surgery as well as the [National Comprehensive Cancer Network] guidelines would be beneficial to long-term survivors of early-stage lung cancer,” Dr. Varlotto and coinvestigators wrote.

“The recent results from recent lung cancer screening studies demonstrate that females may benefit preferentially from screening … and our study suggests that these preferential benefits of increased CT scan surveillance may extend to females who are long-term survivors of lung cancer as well,” they added.
 

Findings in context

“As this is an observational study, it is challenging to understand what is driving the rise in prevalence of second lung cancers,” Mara Antonoff, MD, of The University of Texas MD Anderson Cancer Center in Houston commented in an interview.

“Overall, the findings are very important, as they suggest that we should continue to perform surveillance imaging for patients beyond recommended guidelines, which may allow us to achieve better survival outcomes for those individuals who develop a second lung cancer years after the first lung cancer,” she agreed.

“Just as lung cancer screening is important to identifying lung cancers at an earlier stage when they are more easily treatable and more likely to be cured, surveillance after an initial treatment for lung cancer would allow a diagnosis of second lung cancers at an earlier stage, so the patients can again achieve durable cure,” Dr. Antonoff concluded.

Study details

For the study, Dr. Varlotto and coinvestigators used data from SEER-13 and SEER-18 to identify patients with a lung cancer diagnosis during 1998-2013, and data from SEER-9, covering the years 1985-2014, to calculate rates of second cancers occurring 4-10 years after a first lung cancer.

Analyses were based on 58,758 patients with a surgically resected first primary lung cancer (55.9% with early-stage disease) and 384 patients with a surgically resected second primary lung cancer (77.6% with early-stage disease). Median follow-up was 76 months for the former and 46 months for the latter.

Results showed that in the 4-10 years after a first lung cancer diagnosis, the age-adjusted incidence of second lung cancers rose by study year but remained less than that of all other second cancers combined until the mid-2000s. Among women, incidence started rising sharply in 2001 and significantly exceeded that of all other second cancers starting in 2005.

In the entire population of study patients, propensity-adjusted analyses showed that second lung cancers were similar to first lung cancers on overall survival (P = .1726) but had worse lung cancer–specific survival (P = .0143). However, in the subset of patients with early-stage resectable disease, second and first lung cancers were similar on both overall survival (P = .3872) and lung cancer–specific survival (P = .1276).

Dr. Varlotto disclosed that he had no conflicts of interest. The study was funded by the Department of Radiation Oncology, University of Massachusetts. Dr. Antonoff disclosed that she had no relevant conflicts of interest.

SOURCE: Varlotto JM et al. Lung Cancer. 2020;147:115-122.

Second lung cancers occurring up to a decade after the first are on the rise, but their prognosis is similar – especially when detected early – which supports long-term surveillance in survivors, finds a large population-based study.

Although guidelines recommend continued annual low-dose CT scan surveillance extending beyond 4 years for this population based on expert consensus, long-term evidence of benefit is lacking.

Investigators led by John M. Varlotto, MD, a radiation oncologist at the University of Massachusetts Medical Center, Worcester, analyzed Surveillance, Epidemiology & End Results (SEER) data for more than 58,000 patients with first and sometimes second non–small cell lung cancers initially treated by surgical resection.

Study results reported in Lung Cancer showed that the age-adjusted incidence of second lung cancers occurring 4-10 years after the first lung cancer rose sharply during the 1985-2014 study period, driven by a large uptick in women patients.

Among all patients, second lung cancers had similar overall survival as first lung cancers, but poorer lung cancer–specific survival. However, among the subset of patients having early-stage resectable disease (tumors measuring less than 4 cm with negative nodes), both outcomes were statistically indistinguishable.

“Because our investigation noted that the overall survival of patients undergoing a second lung cancer operation was similar to those patients undergoing a first operation, and because there is a rising rate of second lung cancer in lung cancer survivors, we feel that continued surveillance beyond the 4-year interval as recommended by the American Association for Thoracic Surgery as well as the [National Comprehensive Cancer Network] guidelines would be beneficial to long-term survivors of early-stage lung cancer,” Dr. Varlotto and coinvestigators wrote.

“The recent results from recent lung cancer screening studies demonstrate that females may benefit preferentially from screening … and our study suggests that these preferential benefits of increased CT scan surveillance may extend to females who are long-term survivors of lung cancer as well,” they added.
 

Findings in context

“As this is an observational study, it is challenging to understand what is driving the rise in prevalence of second lung cancers,” Mara Antonoff, MD, of The University of Texas MD Anderson Cancer Center in Houston commented in an interview.

“Overall, the findings are very important, as they suggest that we should continue to perform surveillance imaging for patients beyond recommended guidelines, which may allow us to achieve better survival outcomes for those individuals who develop a second lung cancer years after the first lung cancer,” she agreed.

“Just as lung cancer screening is important to identifying lung cancers at an earlier stage when they are more easily treatable and more likely to be cured, surveillance after an initial treatment for lung cancer would allow a diagnosis of second lung cancers at an earlier stage, so the patients can again achieve durable cure,” Dr. Antonoff concluded.

Study details

For the study, Dr. Varlotto and coinvestigators used data from SEER-13 and SEER-18 to identify patients with a lung cancer diagnosis during 1998-2013, and data from SEER-9, covering the years 1985-2014, to calculate rates of second cancers occurring 4-10 years after a first lung cancer.

Analyses were based on 58,758 patients with a surgically resected first primary lung cancer (55.9% with early-stage disease) and 384 patients with a surgically resected second primary lung cancer (77.6% with early-stage disease). Median follow-up was 76 months for the former and 46 months for the latter.

Results showed that in the 4-10 years after a first lung cancer diagnosis, the age-adjusted incidence of second lung cancers rose by study year but remained less than that of all other second cancers combined until the mid-2000s. Among women, incidence started rising sharply in 2001 and significantly exceeded that of all other second cancers starting in 2005.

In the entire population of study patients, propensity-adjusted analyses showed that second lung cancers were similar to first lung cancers on overall survival (P = .1726) but had worse lung cancer–specific survival (P = .0143). However, in the subset of patients with early-stage resectable disease, second and first lung cancers were similar on both overall survival (P = .3872) and lung cancer–specific survival (P = .1276).

Dr. Varlotto disclosed that he had no conflicts of interest. The study was funded by the Department of Radiation Oncology, University of Massachusetts. Dr. Antonoff disclosed that she had no relevant conflicts of interest.

SOURCE: Varlotto JM et al. Lung Cancer. 2020;147:115-122.

Second lung cancers occurring up to a decade after the first are on the rise, but their prognosis is similar – especially when detected early – which supports long-term surveillance in survivors, finds a large population-based study.

Although guidelines recommend continued annual low-dose CT scan surveillance extending beyond 4 years for this population based on expert consensus, long-term evidence of benefit is lacking.

Investigators led by John M. Varlotto, MD, a radiation oncologist at the University of Massachusetts Medical Center, Worcester, analyzed Surveillance, Epidemiology & End Results (SEER) data for more than 58,000 patients with first and sometimes second non–small cell lung cancers initially treated by surgical resection.

Study results reported in Lung Cancer showed that the age-adjusted incidence of second lung cancers occurring 4-10 years after the first lung cancer rose sharply during the 1985-2014 study period, driven by a large uptick in women patients.

Among all patients, second lung cancers had similar overall survival as first lung cancers, but poorer lung cancer–specific survival. However, among the subset of patients having early-stage resectable disease (tumors measuring less than 4 cm with negative nodes), both outcomes were statistically indistinguishable.

“Because our investigation noted that the overall survival of patients undergoing a second lung cancer operation was similar to those patients undergoing a first operation, and because there is a rising rate of second lung cancer in lung cancer survivors, we feel that continued surveillance beyond the 4-year interval as recommended by the American Association for Thoracic Surgery as well as the [National Comprehensive Cancer Network] guidelines would be beneficial to long-term survivors of early-stage lung cancer,” Dr. Varlotto and coinvestigators wrote.

“The recent results from recent lung cancer screening studies demonstrate that females may benefit preferentially from screening … and our study suggests that these preferential benefits of increased CT scan surveillance may extend to females who are long-term survivors of lung cancer as well,” they added.
 

Findings in context

“As this is an observational study, it is challenging to understand what is driving the rise in prevalence of second lung cancers,” Mara Antonoff, MD, of The University of Texas MD Anderson Cancer Center in Houston commented in an interview.

“Overall, the findings are very important, as they suggest that we should continue to perform surveillance imaging for patients beyond recommended guidelines, which may allow us to achieve better survival outcomes for those individuals who develop a second lung cancer years after the first lung cancer,” she agreed.

“Just as lung cancer screening is important to identifying lung cancers at an earlier stage when they are more easily treatable and more likely to be cured, surveillance after an initial treatment for lung cancer would allow a diagnosis of second lung cancers at an earlier stage, so the patients can again achieve durable cure,” Dr. Antonoff concluded.

Study details

For the study, Dr. Varlotto and coinvestigators used data from SEER-13 and SEER-18 to identify patients with a lung cancer diagnosis during 1998-2013, and data from SEER-9, covering the years 1985-2014, to calculate rates of second cancers occurring 4-10 years after a first lung cancer.

Analyses were based on 58,758 patients with a surgically resected first primary lung cancer (55.9% with early-stage disease) and 384 patients with a surgically resected second primary lung cancer (77.6% with early-stage disease). Median follow-up was 76 months for the former and 46 months for the latter.

Results showed that in the 4-10 years after a first lung cancer diagnosis, the age-adjusted incidence of second lung cancers rose by study year but remained less than that of all other second cancers combined until the mid-2000s. Among women, incidence started rising sharply in 2001 and significantly exceeded that of all other second cancers starting in 2005.

In the entire population of study patients, propensity-adjusted analyses showed that second lung cancers were similar to first lung cancers on overall survival (P = .1726) but had worse lung cancer–specific survival (P = .0143). However, in the subset of patients with early-stage resectable disease, second and first lung cancers were similar on both overall survival (P = .3872) and lung cancer–specific survival (P = .1276).

Dr. Varlotto disclosed that he had no conflicts of interest. The study was funded by the Department of Radiation Oncology, University of Massachusetts. Dr. Antonoff disclosed that she had no relevant conflicts of interest.

SOURCE: Varlotto JM et al. Lung Cancer. 2020;147:115-122.