Article

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.

There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.¹

On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).² Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.³ We reviewed the literature for approaches that were available before and after the date of the index case reported here.

Case Presentation

A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.

Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).

Literature Review

A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).⁴ However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).⁵

A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.^6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.²

A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.⁸ A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.⁹A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.¹

Discussion

The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.¹⁰ In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.

This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.¹¹ This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.¹² Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.

Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.¹³ Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.^6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.¹⁴

Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.^15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.¹⁷ At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.

Conclusions

Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.

Acknowledgments

The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.

There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.¹

On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).² Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.³ We reviewed the literature for approaches that were available before and after the date of the index case reported here.

Case Presentation

A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.

Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).

Literature Review

A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).⁴ However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).⁵

A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.^6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.²

A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.⁸ A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.⁹A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.¹

Discussion

The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.¹⁰ In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.

This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.¹¹ This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.¹² Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.

Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.¹³ Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.^6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.¹⁴

Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.^15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.¹⁷ At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.

Conclusions

Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.

Acknowledgments

The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.

There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.¹

On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).² Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.³ We reviewed the literature for approaches that were available before and after the date of the index case reported here.

Case Presentation

A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.

Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).

Literature Review

A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).⁴ However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).⁵

A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.^6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.²

A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.⁸ A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.⁹A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.¹

Discussion

The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.¹⁰ In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.

This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.¹¹ This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.¹² Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.

Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.¹³ Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.^6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.¹⁴

Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.^15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.¹⁷ At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.

Conclusions

Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.

Acknowledgments

The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.

Suicide is the tenth leading cause of death in the United States claiming nearly 48,000 individuals in 2019 and is the second leading cause of death among individuals aged 10 to 34 years.¹ From 1999 to 2019, the suicide rate increased by 33%.¹ In a retrospective study evaluating suicide risk in > 29,000 men, veterans had a greater risk for suicide in all age groups except for the oldest when compared with nonveterans.² Another study of > 800,000 veterans found that younger veterans were most at risk for suicide.³ Veterans with completed suicides have a high incidence of affective disorders comorbid with substance use disorders, and therefore it is imperative to optimally treat these conditions to address suicidality.⁴ Additionally, a retrospective case-control study of veterans who died by suicide matched to controls identified that the cases had significantly higher rates of mental health conditions and suicidal ideation. Given that the veteran population is at higher risk of suicide, research of treatments to address suicidal ideation in veterans is needed.⁵

Lithium and Antisuicidal Properties

Lithium is the oldest treatment for bipolar disorder and is a long-standing first-line option due to its well-established efficacy as a mood stabilizer.⁶ Lithium’s antisuicidal properties separate it from the other pharmacologic options for bipolar disorder. A possible explanation for lithium’s unique antisuicidal properties is that these effects are mediated by its impact on aggression and impulsivity, which are both linked to an increased suicide risk.^7,8 A meta-analysis by Baldessarini and colleagues demonstrated that patients with mood disorders who were prescribed lithium had a 5 times lower risk of suicide and attempts than did those not treated with lithium.⁹ Lithium’s current place in therapy is in the treatment of bipolar disorder and major depressive disorder augmentation.^10-12Smith and colleagues found that in a cohort study of 21,194 veterans diagnosed with mental health conditions and initiated on lithium or valproate, there were no significant differences in associations with suicide observed between these agents over 365 days; however, there was a significant increased risk of suicide among patients discontinuing or modifying lithium within the first 180 days of treatment.¹³

Currently, lithium is thought to be underutilized at the US Department of Veterans Affairs (VA) Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, Texas, based on the number of prescriptions of lithium in the large population of veterans seen by mental health clinicians. MEDVAMC is a 538-bed academic teaching hospital serving approximately 130,000 veterans in southeast Texas. The Mental Health Care Line has 73 inpatient beds and an outpatient clinic serving > 12,000 patients annually. By retrospectively evaluating changes in suicidality in a sample of veterans prescribed lithium, we may be able to better understand the role that lithium plays in a population that has a higher suicide rate than does the general population. The primary objective of this study was to evaluate the change in number of suicide attempts from 3 months prior to lithium initiation to 3 months following a 6-month duration of lithium use. The secondary objective was to determine the change in suicidal ideation from the period prior to lithium use to the period following 6 months of lithium use.

Methods

This was a single-site, retrospective chart review conducted between October 2017 and April 2018. Prior to data collection, the MEDVAMC Research and Development committee approved the study as quality assurance research. Patients with an active lithium prescription were identified using the VA Lithium Lab Monitoring Dashboard, which includes all patients on lithium, their lithium level, and other data such as upcoming appointments.

Inclusion criteria consisted of adults who were aged ≥ 18 years, had an active lithium prescription on the date of data extraction, and had an active lithium prescription for at least 6 months. Patients were excluded if they had < 3 months of data before and/or after lithium was used for 6 months, and if they were initiated on lithium outside MEDVAMC. Cumulatively, patients had to have at least 12 months of data: 3 months prior to lithium use, at least 6 months of lithium use, and 9 months after lithium initiation.

Suicide Attempt and Suicidal Ideation Identification

When determining the number of suicide attempts, we recorded 4 data points: Veterans Crisis Line notes documenting suicide attempts, hospital admissions for suicide attempts, suicide behavior reports within the indicated time frame, and mental health progress notes documenting suicide attempts. Suicidal ideation was measured in 4 ways. First, we looked at the percentage of outpatient mental health progress notes documenting suicidal ideation. Second, using the Patient Health Questionnaire-9 (PHQ-9) depression assessments, we looked at the percentage of patients that indicated several days, more than half the days, or nearly every day to the question, “Thoughts that you would be better off dead or of hurting yourself in some way.”¹⁴ Third, we recorded the percentage of suicide risk assessments that patients responded yes to both questions on current preoccupation with suicidal thoughts and serious intent and plan to commit suicide with access to guns, stashed pills, or other means. Finally, we noted the percentage of suicide risk assessments where the assessment of risk was moderate or high.

A retrospective electronic health record (EHR) review was performed and the following information was obtained: patient demographics, lithium refill history, concomitant psychotropic medications and psychotherapy, lithium levels, comorbidities at lithium initiation, presence of a high-risk suicide flag in the EHR, suicide risk assessments, suicide behavior reports, Veteran Crisis Line notes, PHQ-9 assessments, and hospital admission and mental health outpatient notes. The lithium therapeutic range of 0.6-1.2 mmol/L is indicated for bipolar disorder and not other indications where the dose is typically titrated to effect rather than level. Medication possession ratio (MPR) was also calculated for lithium (sum of days’ supply for all fills in period ÷ number of days in period). A high-risk suicide flag alerts clinicians and staff that a mental health professional considers the veteran at risk for suicide.¹⁵ Statistical analysis was performed using the paired t test for means to assess proportional differences between variables for the primary and secondary outcomes. Descriptive statistics were used to describe the baseline characteristics.

Results

A total of 214 patients with an active prescription for lithium were identified on the Lithium Lab Monitoring Dashboard on October 31, 2017. After exclusion criteria were applied, 98 patients were included in the study (Figure 1). The 2 most common reasons for exclusion were due to patients not being on lithium for at least 6 months and being initiated on lithium at an outside facility. One patient was enrolled in a lithium research study (the medication ordered was lithium/placebo) and another patient refused all psychotropic medications according to the progress notes.

Most of the 98 patients (82.7%) were male with average age 50.5 years (Table 1). Almost half the patients (n = 47) were concomitantly participating in psychotherapy, and 50 (51.0%) patients received at least 1 antipsychotic medication. Twenty-nine patients had an active prescription for an additional mood stabilizer, and only 4 (4.1%) patients received lithium as monotherapy. Only 75 (76.5%) patients had a lithium level drawn during the 6 months of therapy, with 28 (37.3%) patients having a therapeutic lithium level (0.6 - 1.2 mmol/L). Seventy-one patients (72.4% ) were adherent to lithium therapy with a MPR > 0.8.¹⁶ Participants had 13 different psychiatric diagnoses at the time of lithium initiation; the most common were bipolar spectrum disorder (n = 38; 38.8%), depressive disorder (n = 27; 27.6%), and posttraumatic stress disorder (PTSD) (n = 26; 26.5%). Of note, 5 patients had a diagnosis of only PTSD without a concomitant mood disorder.

Discussion

The results of this study suggest lithium may have a role in reducing suicidality in a veteran population. There was a statistically significant reduction in hospitalizations for suicide attempt and suicidal ideation after at least 6 months of lithium use. These results are comparable with a previously published study that observed significant decreases in suicidal behavior and/or hospitalization risks among veterans taking lithium compared with those not taking lithium.¹⁷ Our study was similar in respect to the reduced hospitalizations among a veteran population; however, the previous study did not report a difference in suicide attempts and lithium use. This could be related to the longer follow-up time in the previous study (3 years) vs our study (9 months).

Our study identified a significant reduction in Veteran Crisis Line calls after at least 6 months of lithium use. While a reduction in suicidal ideations could be implicated in the decrease in crisis line calls, there may be a confounding variable. It is possible that after lithium initiation, veterans had more frequent contact with health care practitioners due to laboratory test monitoring and follow-up visits and thus had concerns/crises addressed during these interactions ultimately leading to a decreased utilization of the crisis line. Interestingly, there was a reduction in mental health outpatient notes from the prelithium period to the 3-month period that followed 6 months of lithium therapy. However, our study did not report on the number of mental health outpatient notes or visits during the 6-month lithium duration. Additionally, time of year/season could have an impact on suicidality, but this relationship was not evaluated in this study.

The presence of high-risk suicide flags also decreased from the prelithium period to the period 3 months following 6 months of lithium use. High-risk flags are reviewed by the suicide prevention coordinators and mental health professionals every 90 days; therefore, the patients with flags had multiple opportunities for review and thus renewal or discontinuation during the study period. A similar rationale can be applied to the high-risk flag as with the Veteran Crisis Line reduction, although this change could also be representative of a decrease in suicidality. Our study is different from other lithium studies because it included patients with a multitude of psychiatric diagnoses rather than just mood disorders. Five of the patients had a diagnosis of only PTSD and no documented mood disorder at the time of lithium initiation. Additional research is needed on the impact of lithium on suicidality in veterans with PTSD and psychiatric conditions other than mood disorders.

Underutilization of Lithium

Despite widespread knowledge of lithium’s antisuicidal effects, it is underutilized as a mood stabilizer in the US.¹⁸ There are various modifiable barriers that impact the prescribing as well as use of lithium. Clinicians may not be fully aware of lithium’s antisuicidal properties and may also have a low level of confidence in patients’ likelihood of adherence to laboratory monitoring.^18,19 Due to the narrow therapeutic index of lithium, the consequences of nonadherence to monitoring can be dangerous, which may deter mental health professionals from prescribing this antisuicidal agent. At MEDVAMC, only 72.4% of patients with a lithium prescription had a lithium level drawn within a 6-month period. This could be attributed to patient nonadherence (eg, the test was ordered but the patient did not go) or clinician nonadherence (eg, test was not ordered).

With increased clinician education as well as clinics dedicated to lithium management that allow for closer follow-up, facilities may see an increased level of comfort with lithium use. Lithium management clinics that provide close follow-up may also help address patient-related concerns about adverse effects and allow for close monitoring. To facilitate lithium monitoring at MEDVAMC, mental health practitioners and pharmacists developed a lithium test monitoring menu that serves as a “one-stop shop” for lithium baseline and ongoing test results.

In the future, we may study the impact of this test monitoring menu on lithium prescribing. One may also consider whether lithium levels need to be monitored at different frequencies (eg, less frequently for depression than bipolar disorder) depending on the diagnoses. A better understanding of the necessity for therapeutic monitoring may potentially reduce barriers to prescribing for patients who do not have indications that have a recommended therapeutic range (eg, bipolar disorder).

Lithium Adherence

A primary patient-related concern for low lithium utilization is poor adherence. In this sample, 71 patients (72.4%) were considered fully adherent. This was higher than the rate of 54.1% reported by Sajatovic and colleagues in a study evaluating adherence to lithium and other anticonvulsants in veterans with bipolar disorder.²⁰ Patients’ beliefs about medications and overall health as well as knowledge of the illness and treatment may impact adherence.²¹ The literature indicates that strategies such as cognitive behavioral therapy (CBT) and didactic lectures positively impact patients’ attitudes about lithium, which ultimately influences adherence.^21-23 Involving a family member or significant other in psychotherapy may also improve lithium adherence.²¹ Specifically in the VA, to address knowledge deficits and improve overall adherence, the Lithium Lab Monitoring Dashboard could be used to identify and invite new lithium starts to educational groups about lithium. These groups could also serve as lithium management clinics.

Limitations

There were several limitations to this study. This was a single-site, retrospective chart review with a small sample size. We studied a cross-section of veterans with only active prescriptions, which limited the sample size. The results should be interpreted cautiously because < 40% of patients who had a level drawn were in the therapeutic range. Patients whose lithium levels were outside of the therapeutic range may have not been fully adherent to the medication. Further analysis based on reason for lithium prescription (eg, bipolar disorder vs depression vs aggression/impulsivity in PTSD) may be helpful in better understanding the results.

Additionally, while we collected data on concomitant mood stabilizers and antipsychotics, we did not collect data on concurrent antidepressant therapy and only 4% of patients were on lithium monotherapy. Data regarding veterans undergoing concurrent CBT during their lithium trial were not assessed in this study and could be considered a confounding factor for future studies. We included any Veteran Crisis Line call in our results regardless of the reason for the call, which could have led to overreporting of this suicidality marker.

Given its small sample size, this study should be considered as hypothesis-generating. Further studies are needed to address lithium’s antisuicidal effects in specific diagnoses (eg, PTSD, anxiety, schizoaffective disorder) to better understand its place in therapy. Studies evaluating the relationship between dosing and suicidality may help provide insight into whether the antisuicidal effect of lithium is dose-dependent and whether a specific dose range rather than a therapeutic level should be targeted for antisuicidal purposes.

Conclusions

People treated for an affective disorder have a 30-times greater risk of suicide than do those in the general population; however, as lithium can reduce the risk of suicide and self-harm, it should continue to have an important role in clinical practice.²⁴ At MEDVAMC, we observed a statistically significant reduction in hospitalization for suicide attempts and suicidal ideation in veterans prescribed lithium following nonfatal suicide behavior and suicidal ideation. Prospective randomized placebo-controlled studies are needed to better understand lithium’s antisuicidal effects.

Suicide is the tenth leading cause of death in the United States claiming nearly 48,000 individuals in 2019 and is the second leading cause of death among individuals aged 10 to 34 years.¹ From 1999 to 2019, the suicide rate increased by 33%.¹ In a retrospective study evaluating suicide risk in > 29,000 men, veterans had a greater risk for suicide in all age groups except for the oldest when compared with nonveterans.² Another study of > 800,000 veterans found that younger veterans were most at risk for suicide.³ Veterans with completed suicides have a high incidence of affective disorders comorbid with substance use disorders, and therefore it is imperative to optimally treat these conditions to address suicidality.⁴ Additionally, a retrospective case-control study of veterans who died by suicide matched to controls identified that the cases had significantly higher rates of mental health conditions and suicidal ideation. Given that the veteran population is at higher risk of suicide, research of treatments to address suicidal ideation in veterans is needed.⁵

Lithium and Antisuicidal Properties

Lithium is the oldest treatment for bipolar disorder and is a long-standing first-line option due to its well-established efficacy as a mood stabilizer.⁶ Lithium’s antisuicidal properties separate it from the other pharmacologic options for bipolar disorder. A possible explanation for lithium’s unique antisuicidal properties is that these effects are mediated by its impact on aggression and impulsivity, which are both linked to an increased suicide risk.^7,8 A meta-analysis by Baldessarini and colleagues demonstrated that patients with mood disorders who were prescribed lithium had a 5 times lower risk of suicide and attempts than did those not treated with lithium.⁹ Lithium’s current place in therapy is in the treatment of bipolar disorder and major depressive disorder augmentation.^10-12Smith and colleagues found that in a cohort study of 21,194 veterans diagnosed with mental health conditions and initiated on lithium or valproate, there were no significant differences in associations with suicide observed between these agents over 365 days; however, there was a significant increased risk of suicide among patients discontinuing or modifying lithium within the first 180 days of treatment.¹³

Currently, lithium is thought to be underutilized at the US Department of Veterans Affairs (VA) Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, Texas, based on the number of prescriptions of lithium in the large population of veterans seen by mental health clinicians. MEDVAMC is a 538-bed academic teaching hospital serving approximately 130,000 veterans in southeast Texas. The Mental Health Care Line has 73 inpatient beds and an outpatient clinic serving > 12,000 patients annually. By retrospectively evaluating changes in suicidality in a sample of veterans prescribed lithium, we may be able to better understand the role that lithium plays in a population that has a higher suicide rate than does the general population. The primary objective of this study was to evaluate the change in number of suicide attempts from 3 months prior to lithium initiation to 3 months following a 6-month duration of lithium use. The secondary objective was to determine the change in suicidal ideation from the period prior to lithium use to the period following 6 months of lithium use.

Methods

This was a single-site, retrospective chart review conducted between October 2017 and April 2018. Prior to data collection, the MEDVAMC Research and Development committee approved the study as quality assurance research. Patients with an active lithium prescription were identified using the VA Lithium Lab Monitoring Dashboard, which includes all patients on lithium, their lithium level, and other data such as upcoming appointments.

Inclusion criteria consisted of adults who were aged ≥ 18 years, had an active lithium prescription on the date of data extraction, and had an active lithium prescription for at least 6 months. Patients were excluded if they had < 3 months of data before and/or after lithium was used for 6 months, and if they were initiated on lithium outside MEDVAMC. Cumulatively, patients had to have at least 12 months of data: 3 months prior to lithium use, at least 6 months of lithium use, and 9 months after lithium initiation.

Suicide Attempt and Suicidal Ideation Identification

When determining the number of suicide attempts, we recorded 4 data points: Veterans Crisis Line notes documenting suicide attempts, hospital admissions for suicide attempts, suicide behavior reports within the indicated time frame, and mental health progress notes documenting suicide attempts. Suicidal ideation was measured in 4 ways. First, we looked at the percentage of outpatient mental health progress notes documenting suicidal ideation. Second, using the Patient Health Questionnaire-9 (PHQ-9) depression assessments, we looked at the percentage of patients that indicated several days, more than half the days, or nearly every day to the question, “Thoughts that you would be better off dead or of hurting yourself in some way.”¹⁴ Third, we recorded the percentage of suicide risk assessments that patients responded yes to both questions on current preoccupation with suicidal thoughts and serious intent and plan to commit suicide with access to guns, stashed pills, or other means. Finally, we noted the percentage of suicide risk assessments where the assessment of risk was moderate or high.

A retrospective electronic health record (EHR) review was performed and the following information was obtained: patient demographics, lithium refill history, concomitant psychotropic medications and psychotherapy, lithium levels, comorbidities at lithium initiation, presence of a high-risk suicide flag in the EHR, suicide risk assessments, suicide behavior reports, Veteran Crisis Line notes, PHQ-9 assessments, and hospital admission and mental health outpatient notes. The lithium therapeutic range of 0.6-1.2 mmol/L is indicated for bipolar disorder and not other indications where the dose is typically titrated to effect rather than level. Medication possession ratio (MPR) was also calculated for lithium (sum of days’ supply for all fills in period ÷ number of days in period). A high-risk suicide flag alerts clinicians and staff that a mental health professional considers the veteran at risk for suicide.¹⁵ Statistical analysis was performed using the paired t test for means to assess proportional differences between variables for the primary and secondary outcomes. Descriptive statistics were used to describe the baseline characteristics.

Results

A total of 214 patients with an active prescription for lithium were identified on the Lithium Lab Monitoring Dashboard on October 31, 2017. After exclusion criteria were applied, 98 patients were included in the study (Figure 1). The 2 most common reasons for exclusion were due to patients not being on lithium for at least 6 months and being initiated on lithium at an outside facility. One patient was enrolled in a lithium research study (the medication ordered was lithium/placebo) and another patient refused all psychotropic medications according to the progress notes.

Most of the 98 patients (82.7%) were male with average age 50.5 years (Table 1). Almost half the patients (n = 47) were concomitantly participating in psychotherapy, and 50 (51.0%) patients received at least 1 antipsychotic medication. Twenty-nine patients had an active prescription for an additional mood stabilizer, and only 4 (4.1%) patients received lithium as monotherapy. Only 75 (76.5%) patients had a lithium level drawn during the 6 months of therapy, with 28 (37.3%) patients having a therapeutic lithium level (0.6 - 1.2 mmol/L). Seventy-one patients (72.4% ) were adherent to lithium therapy with a MPR > 0.8.¹⁶ Participants had 13 different psychiatric diagnoses at the time of lithium initiation; the most common were bipolar spectrum disorder (n = 38; 38.8%), depressive disorder (n = 27; 27.6%), and posttraumatic stress disorder (PTSD) (n = 26; 26.5%). Of note, 5 patients had a diagnosis of only PTSD without a concomitant mood disorder.

Discussion

The results of this study suggest lithium may have a role in reducing suicidality in a veteran population. There was a statistically significant reduction in hospitalizations for suicide attempt and suicidal ideation after at least 6 months of lithium use. These results are comparable with a previously published study that observed significant decreases in suicidal behavior and/or hospitalization risks among veterans taking lithium compared with those not taking lithium.¹⁷ Our study was similar in respect to the reduced hospitalizations among a veteran population; however, the previous study did not report a difference in suicide attempts and lithium use. This could be related to the longer follow-up time in the previous study (3 years) vs our study (9 months).

Our study identified a significant reduction in Veteran Crisis Line calls after at least 6 months of lithium use. While a reduction in suicidal ideations could be implicated in the decrease in crisis line calls, there may be a confounding variable. It is possible that after lithium initiation, veterans had more frequent contact with health care practitioners due to laboratory test monitoring and follow-up visits and thus had concerns/crises addressed during these interactions ultimately leading to a decreased utilization of the crisis line. Interestingly, there was a reduction in mental health outpatient notes from the prelithium period to the 3-month period that followed 6 months of lithium therapy. However, our study did not report on the number of mental health outpatient notes or visits during the 6-month lithium duration. Additionally, time of year/season could have an impact on suicidality, but this relationship was not evaluated in this study.

The presence of high-risk suicide flags also decreased from the prelithium period to the period 3 months following 6 months of lithium use. High-risk flags are reviewed by the suicide prevention coordinators and mental health professionals every 90 days; therefore, the patients with flags had multiple opportunities for review and thus renewal or discontinuation during the study period. A similar rationale can be applied to the high-risk flag as with the Veteran Crisis Line reduction, although this change could also be representative of a decrease in suicidality. Our study is different from other lithium studies because it included patients with a multitude of psychiatric diagnoses rather than just mood disorders. Five of the patients had a diagnosis of only PTSD and no documented mood disorder at the time of lithium initiation. Additional research is needed on the impact of lithium on suicidality in veterans with PTSD and psychiatric conditions other than mood disorders.

Underutilization of Lithium

Despite widespread knowledge of lithium’s antisuicidal effects, it is underutilized as a mood stabilizer in the US.¹⁸ There are various modifiable barriers that impact the prescribing as well as use of lithium. Clinicians may not be fully aware of lithium’s antisuicidal properties and may also have a low level of confidence in patients’ likelihood of adherence to laboratory monitoring.^18,19 Due to the narrow therapeutic index of lithium, the consequences of nonadherence to monitoring can be dangerous, which may deter mental health professionals from prescribing this antisuicidal agent. At MEDVAMC, only 72.4% of patients with a lithium prescription had a lithium level drawn within a 6-month period. This could be attributed to patient nonadherence (eg, the test was ordered but the patient did not go) or clinician nonadherence (eg, test was not ordered).

With increased clinician education as well as clinics dedicated to lithium management that allow for closer follow-up, facilities may see an increased level of comfort with lithium use. Lithium management clinics that provide close follow-up may also help address patient-related concerns about adverse effects and allow for close monitoring. To facilitate lithium monitoring at MEDVAMC, mental health practitioners and pharmacists developed a lithium test monitoring menu that serves as a “one-stop shop” for lithium baseline and ongoing test results.

In the future, we may study the impact of this test monitoring menu on lithium prescribing. One may also consider whether lithium levels need to be monitored at different frequencies (eg, less frequently for depression than bipolar disorder) depending on the diagnoses. A better understanding of the necessity for therapeutic monitoring may potentially reduce barriers to prescribing for patients who do not have indications that have a recommended therapeutic range (eg, bipolar disorder).

Lithium Adherence

A primary patient-related concern for low lithium utilization is poor adherence. In this sample, 71 patients (72.4%) were considered fully adherent. This was higher than the rate of 54.1% reported by Sajatovic and colleagues in a study evaluating adherence to lithium and other anticonvulsants in veterans with bipolar disorder.²⁰ Patients’ beliefs about medications and overall health as well as knowledge of the illness and treatment may impact adherence.²¹ The literature indicates that strategies such as cognitive behavioral therapy (CBT) and didactic lectures positively impact patients’ attitudes about lithium, which ultimately influences adherence.^21-23 Involving a family member or significant other in psychotherapy may also improve lithium adherence.²¹ Specifically in the VA, to address knowledge deficits and improve overall adherence, the Lithium Lab Monitoring Dashboard could be used to identify and invite new lithium starts to educational groups about lithium. These groups could also serve as lithium management clinics.

Limitations

There were several limitations to this study. This was a single-site, retrospective chart review with a small sample size. We studied a cross-section of veterans with only active prescriptions, which limited the sample size. The results should be interpreted cautiously because < 40% of patients who had a level drawn were in the therapeutic range. Patients whose lithium levels were outside of the therapeutic range may have not been fully adherent to the medication. Further analysis based on reason for lithium prescription (eg, bipolar disorder vs depression vs aggression/impulsivity in PTSD) may be helpful in better understanding the results.

Additionally, while we collected data on concomitant mood stabilizers and antipsychotics, we did not collect data on concurrent antidepressant therapy and only 4% of patients were on lithium monotherapy. Data regarding veterans undergoing concurrent CBT during their lithium trial were not assessed in this study and could be considered a confounding factor for future studies. We included any Veteran Crisis Line call in our results regardless of the reason for the call, which could have led to overreporting of this suicidality marker.

Given its small sample size, this study should be considered as hypothesis-generating. Further studies are needed to address lithium’s antisuicidal effects in specific diagnoses (eg, PTSD, anxiety, schizoaffective disorder) to better understand its place in therapy. Studies evaluating the relationship between dosing and suicidality may help provide insight into whether the antisuicidal effect of lithium is dose-dependent and whether a specific dose range rather than a therapeutic level should be targeted for antisuicidal purposes.

Conclusions

People treated for an affective disorder have a 30-times greater risk of suicide than do those in the general population; however, as lithium can reduce the risk of suicide and self-harm, it should continue to have an important role in clinical practice.²⁴ At MEDVAMC, we observed a statistically significant reduction in hospitalization for suicide attempts and suicidal ideation in veterans prescribed lithium following nonfatal suicide behavior and suicidal ideation. Prospective randomized placebo-controlled studies are needed to better understand lithium’s antisuicidal effects.

Suicide is the tenth leading cause of death in the United States claiming nearly 48,000 individuals in 2019 and is the second leading cause of death among individuals aged 10 to 34 years.¹ From 1999 to 2019, the suicide rate increased by 33%.¹ In a retrospective study evaluating suicide risk in > 29,000 men, veterans had a greater risk for suicide in all age groups except for the oldest when compared with nonveterans.² Another study of > 800,000 veterans found that younger veterans were most at risk for suicide.³ Veterans with completed suicides have a high incidence of affective disorders comorbid with substance use disorders, and therefore it is imperative to optimally treat these conditions to address suicidality.⁴ Additionally, a retrospective case-control study of veterans who died by suicide matched to controls identified that the cases had significantly higher rates of mental health conditions and suicidal ideation. Given that the veteran population is at higher risk of suicide, research of treatments to address suicidal ideation in veterans is needed.⁵

Lithium and Antisuicidal Properties

Lithium is the oldest treatment for bipolar disorder and is a long-standing first-line option due to its well-established efficacy as a mood stabilizer.⁶ Lithium’s antisuicidal properties separate it from the other pharmacologic options for bipolar disorder. A possible explanation for lithium’s unique antisuicidal properties is that these effects are mediated by its impact on aggression and impulsivity, which are both linked to an increased suicide risk.^7,8 A meta-analysis by Baldessarini and colleagues demonstrated that patients with mood disorders who were prescribed lithium had a 5 times lower risk of suicide and attempts than did those not treated with lithium.⁹ Lithium’s current place in therapy is in the treatment of bipolar disorder and major depressive disorder augmentation.^10-12Smith and colleagues found that in a cohort study of 21,194 veterans diagnosed with mental health conditions and initiated on lithium or valproate, there were no significant differences in associations with suicide observed between these agents over 365 days; however, there was a significant increased risk of suicide among patients discontinuing or modifying lithium within the first 180 days of treatment.¹³

Currently, lithium is thought to be underutilized at the US Department of Veterans Affairs (VA) Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, Texas, based on the number of prescriptions of lithium in the large population of veterans seen by mental health clinicians. MEDVAMC is a 538-bed academic teaching hospital serving approximately 130,000 veterans in southeast Texas. The Mental Health Care Line has 73 inpatient beds and an outpatient clinic serving > 12,000 patients annually. By retrospectively evaluating changes in suicidality in a sample of veterans prescribed lithium, we may be able to better understand the role that lithium plays in a population that has a higher suicide rate than does the general population. The primary objective of this study was to evaluate the change in number of suicide attempts from 3 months prior to lithium initiation to 3 months following a 6-month duration of lithium use. The secondary objective was to determine the change in suicidal ideation from the period prior to lithium use to the period following 6 months of lithium use.

Methods

This was a single-site, retrospective chart review conducted between October 2017 and April 2018. Prior to data collection, the MEDVAMC Research and Development committee approved the study as quality assurance research. Patients with an active lithium prescription were identified using the VA Lithium Lab Monitoring Dashboard, which includes all patients on lithium, their lithium level, and other data such as upcoming appointments.

Inclusion criteria consisted of adults who were aged ≥ 18 years, had an active lithium prescription on the date of data extraction, and had an active lithium prescription for at least 6 months. Patients were excluded if they had < 3 months of data before and/or after lithium was used for 6 months, and if they were initiated on lithium outside MEDVAMC. Cumulatively, patients had to have at least 12 months of data: 3 months prior to lithium use, at least 6 months of lithium use, and 9 months after lithium initiation.

Suicide Attempt and Suicidal Ideation Identification

When determining the number of suicide attempts, we recorded 4 data points: Veterans Crisis Line notes documenting suicide attempts, hospital admissions for suicide attempts, suicide behavior reports within the indicated time frame, and mental health progress notes documenting suicide attempts. Suicidal ideation was measured in 4 ways. First, we looked at the percentage of outpatient mental health progress notes documenting suicidal ideation. Second, using the Patient Health Questionnaire-9 (PHQ-9) depression assessments, we looked at the percentage of patients that indicated several days, more than half the days, or nearly every day to the question, “Thoughts that you would be better off dead or of hurting yourself in some way.”¹⁴ Third, we recorded the percentage of suicide risk assessments that patients responded yes to both questions on current preoccupation with suicidal thoughts and serious intent and plan to commit suicide with access to guns, stashed pills, or other means. Finally, we noted the percentage of suicide risk assessments where the assessment of risk was moderate or high.

A retrospective electronic health record (EHR) review was performed and the following information was obtained: patient demographics, lithium refill history, concomitant psychotropic medications and psychotherapy, lithium levels, comorbidities at lithium initiation, presence of a high-risk suicide flag in the EHR, suicide risk assessments, suicide behavior reports, Veteran Crisis Line notes, PHQ-9 assessments, and hospital admission and mental health outpatient notes. The lithium therapeutic range of 0.6-1.2 mmol/L is indicated for bipolar disorder and not other indications where the dose is typically titrated to effect rather than level. Medication possession ratio (MPR) was also calculated for lithium (sum of days’ supply for all fills in period ÷ number of days in period). A high-risk suicide flag alerts clinicians and staff that a mental health professional considers the veteran at risk for suicide.¹⁵ Statistical analysis was performed using the paired t test for means to assess proportional differences between variables for the primary and secondary outcomes. Descriptive statistics were used to describe the baseline characteristics.

Results

A total of 214 patients with an active prescription for lithium were identified on the Lithium Lab Monitoring Dashboard on October 31, 2017. After exclusion criteria were applied, 98 patients were included in the study (Figure 1). The 2 most common reasons for exclusion were due to patients not being on lithium for at least 6 months and being initiated on lithium at an outside facility. One patient was enrolled in a lithium research study (the medication ordered was lithium/placebo) and another patient refused all psychotropic medications according to the progress notes.

Most of the 98 patients (82.7%) were male with average age 50.5 years (Table 1). Almost half the patients (n = 47) were concomitantly participating in psychotherapy, and 50 (51.0%) patients received at least 1 antipsychotic medication. Twenty-nine patients had an active prescription for an additional mood stabilizer, and only 4 (4.1%) patients received lithium as monotherapy. Only 75 (76.5%) patients had a lithium level drawn during the 6 months of therapy, with 28 (37.3%) patients having a therapeutic lithium level (0.6 - 1.2 mmol/L). Seventy-one patients (72.4% ) were adherent to lithium therapy with a MPR > 0.8.¹⁶ Participants had 13 different psychiatric diagnoses at the time of lithium initiation; the most common were bipolar spectrum disorder (n = 38; 38.8%), depressive disorder (n = 27; 27.6%), and posttraumatic stress disorder (PTSD) (n = 26; 26.5%). Of note, 5 patients had a diagnosis of only PTSD without a concomitant mood disorder.

Discussion

The results of this study suggest lithium may have a role in reducing suicidality in a veteran population. There was a statistically significant reduction in hospitalizations for suicide attempt and suicidal ideation after at least 6 months of lithium use. These results are comparable with a previously published study that observed significant decreases in suicidal behavior and/or hospitalization risks among veterans taking lithium compared with those not taking lithium.¹⁷ Our study was similar in respect to the reduced hospitalizations among a veteran population; however, the previous study did not report a difference in suicide attempts and lithium use. This could be related to the longer follow-up time in the previous study (3 years) vs our study (9 months).

Our study identified a significant reduction in Veteran Crisis Line calls after at least 6 months of lithium use. While a reduction in suicidal ideations could be implicated in the decrease in crisis line calls, there may be a confounding variable. It is possible that after lithium initiation, veterans had more frequent contact with health care practitioners due to laboratory test monitoring and follow-up visits and thus had concerns/crises addressed during these interactions ultimately leading to a decreased utilization of the crisis line. Interestingly, there was a reduction in mental health outpatient notes from the prelithium period to the 3-month period that followed 6 months of lithium therapy. However, our study did not report on the number of mental health outpatient notes or visits during the 6-month lithium duration. Additionally, time of year/season could have an impact on suicidality, but this relationship was not evaluated in this study.

The presence of high-risk suicide flags also decreased from the prelithium period to the period 3 months following 6 months of lithium use. High-risk flags are reviewed by the suicide prevention coordinators and mental health professionals every 90 days; therefore, the patients with flags had multiple opportunities for review and thus renewal or discontinuation during the study period. A similar rationale can be applied to the high-risk flag as with the Veteran Crisis Line reduction, although this change could also be representative of a decrease in suicidality. Our study is different from other lithium studies because it included patients with a multitude of psychiatric diagnoses rather than just mood disorders. Five of the patients had a diagnosis of only PTSD and no documented mood disorder at the time of lithium initiation. Additional research is needed on the impact of lithium on suicidality in veterans with PTSD and psychiatric conditions other than mood disorders.

Underutilization of Lithium

Despite widespread knowledge of lithium’s antisuicidal effects, it is underutilized as a mood stabilizer in the US.¹⁸ There are various modifiable barriers that impact the prescribing as well as use of lithium. Clinicians may not be fully aware of lithium’s antisuicidal properties and may also have a low level of confidence in patients’ likelihood of adherence to laboratory monitoring.^18,19 Due to the narrow therapeutic index of lithium, the consequences of nonadherence to monitoring can be dangerous, which may deter mental health professionals from prescribing this antisuicidal agent. At MEDVAMC, only 72.4% of patients with a lithium prescription had a lithium level drawn within a 6-month period. This could be attributed to patient nonadherence (eg, the test was ordered but the patient did not go) or clinician nonadherence (eg, test was not ordered).

With increased clinician education as well as clinics dedicated to lithium management that allow for closer follow-up, facilities may see an increased level of comfort with lithium use. Lithium management clinics that provide close follow-up may also help address patient-related concerns about adverse effects and allow for close monitoring. To facilitate lithium monitoring at MEDVAMC, mental health practitioners and pharmacists developed a lithium test monitoring menu that serves as a “one-stop shop” for lithium baseline and ongoing test results.

In the future, we may study the impact of this test monitoring menu on lithium prescribing. One may also consider whether lithium levels need to be monitored at different frequencies (eg, less frequently for depression than bipolar disorder) depending on the diagnoses. A better understanding of the necessity for therapeutic monitoring may potentially reduce barriers to prescribing for patients who do not have indications that have a recommended therapeutic range (eg, bipolar disorder).

Lithium Adherence

A primary patient-related concern for low lithium utilization is poor adherence. In this sample, 71 patients (72.4%) were considered fully adherent. This was higher than the rate of 54.1% reported by Sajatovic and colleagues in a study evaluating adherence to lithium and other anticonvulsants in veterans with bipolar disorder.²⁰ Patients’ beliefs about medications and overall health as well as knowledge of the illness and treatment may impact adherence.²¹ The literature indicates that strategies such as cognitive behavioral therapy (CBT) and didactic lectures positively impact patients’ attitudes about lithium, which ultimately influences adherence.^21-23 Involving a family member or significant other in psychotherapy may also improve lithium adherence.²¹ Specifically in the VA, to address knowledge deficits and improve overall adherence, the Lithium Lab Monitoring Dashboard could be used to identify and invite new lithium starts to educational groups about lithium. These groups could also serve as lithium management clinics.

Limitations

There were several limitations to this study. This was a single-site, retrospective chart review with a small sample size. We studied a cross-section of veterans with only active prescriptions, which limited the sample size. The results should be interpreted cautiously because < 40% of patients who had a level drawn were in the therapeutic range. Patients whose lithium levels were outside of the therapeutic range may have not been fully adherent to the medication. Further analysis based on reason for lithium prescription (eg, bipolar disorder vs depression vs aggression/impulsivity in PTSD) may be helpful in better understanding the results.

Additionally, while we collected data on concomitant mood stabilizers and antipsychotics, we did not collect data on concurrent antidepressant therapy and only 4% of patients were on lithium monotherapy. Data regarding veterans undergoing concurrent CBT during their lithium trial were not assessed in this study and could be considered a confounding factor for future studies. We included any Veteran Crisis Line call in our results regardless of the reason for the call, which could have led to overreporting of this suicidality marker.

Given its small sample size, this study should be considered as hypothesis-generating. Further studies are needed to address lithium’s antisuicidal effects in specific diagnoses (eg, PTSD, anxiety, schizoaffective disorder) to better understand its place in therapy. Studies evaluating the relationship between dosing and suicidality may help provide insight into whether the antisuicidal effect of lithium is dose-dependent and whether a specific dose range rather than a therapeutic level should be targeted for antisuicidal purposes.

Conclusions

People treated for an affective disorder have a 30-times greater risk of suicide than do those in the general population; however, as lithium can reduce the risk of suicide and self-harm, it should continue to have an important role in clinical practice.²⁴ At MEDVAMC, we observed a statistically significant reduction in hospitalization for suicide attempts and suicidal ideation in veterans prescribed lithium following nonfatal suicide behavior and suicidal ideation. Prospective randomized placebo-controlled studies are needed to better understand lithium’s antisuicidal effects.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.