ROCKVILLE, MD – If approved for treatment-resistant depression, intranasal esketamine will be strictly regulated in the clinic, with federal monitoring requirements designed to prevent misuse, abuse, or diversion of the drug.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Managed under a Food and Drug Administration Risk Evaluation and Mitigation Strategy (REMS), such a program would establish a stringent post-administration protocol of observation and blood pressure monitoring and require every provider – whether a large health care center or a single clinician – to obtain federal certification to dispense the medication.

At a joint meeting of FDA’s Psychopharmacologic Drugs Advisory and Drug Safety and Risk Management Advisory committees, some members offered a more tempered view while still supporting the approval pathway of the N-methyl-D-aspartate receptor antagonist. By a vote of 14-2, with one abstention, they agreed Feb. 12 that the benefits outweigh the risks of esketamine for treatment-resistant depression.

“I think it has the potential to be a game changer in treatment-resistant depression,” said Walter Dunn, MD, PhD, of the University of California, Los Angeles. “We may someday talk about 2019 in the same way we now talk about the late ’80s, when the first [selective serotonin reuptake inhibitors] were approved.”

Janssen Pharmaceuticals, which is developing the drug, incorporated concerns about misuse from the beginning. Even the delivery device is designed to prevent such issues, a company spokesman said.

• Prescriber training on the risks of esketamine and importance of monitoring patients after their dose is administered and the need to register patients
•  Administration of esketamine only in certain health care settings that ensure patient monitoring by a health care clinician for 2 hours after administration
•  Pharmacies, clinicians, or health care settings that dispense the drug are specially certified to ensure that esketamine is not dispensed directly to patients and that patients are monitored
•  Enrollment of patients who are treated with esketamine in a registry to better characterize the risks associated with esketamine administration and inform risk mitigation strategies

After administration, patients would be monitored for at least 2 hours for the common side effects, sedation and dissociation that typically clear within that time. Transient blood pressure fluctuations also can occur shortly after administration and would be monitored until stable. Patients should also be counseled not to drive the day of treatment, and to bring a companion along to drive them home.

Dr. Dunn, however, suggested that some facets of the proposed REMS might create unnecessary barriers for some patients and that stringent monitoring after every single dose – potentially for years – might not be necessary for everyone.

“The REM is certainly important to address the potential for diversion and misuse and adverse effects, but there needs to be a pathway to reduce monitoring requirements” on an individual basis. “If a patient is doing well for a year or so, in remission with no side effects, we should have a way to reduce the need for monitoring. If we make it too much of a burden to go in, get the medication, stay for a couple of hours for monitoring, it’s easy to skip a dose. And we know the number one predictor of relapse is medication nonadherence.”

The facility certification requirement also could curtail access to esketamine, said Steven B. Meisel, PharmD, of Minneapolis.

“How do we define a medically supervised center? Is it somewhere with a nurse onsite? A physician onsite? Does it have to have access to emergency services? This issue of access vs. control and safety is a very important one.”

He posed a clinical conundrum: A patient doing well on regular esketamine who wants to go on an extended trip. Under the proposed REMS, that patient would not be able to access his regular dose, which could only be handled, sorted, and administered by a certified health care clinician. “How are we going to deal with this? There will be great pressure to loosen this up in some manner. But if we allow a patient who’s been doing well on regular treatment with no relapse to have this at home, do we open the way for a teenager to take a bottle or two to a party? Those are real-world issues and must be considered when we establish a REM in a real world that demands access to needed therapy.”

Erring on the side of caution is the responsibility of policymakers, argued Kim Witczak, executive director of Woodymatters, a consumer-driven, nonprofit drug safety organization dedicated to FDA reform. Ms. Witczak was one of two dissenting voices on the vote.

“This has so much potential for so many people who just want a quick fix [for their mood disorders], and the marketing side will see this,” she predicted. “I would want to be very cautious. Once it gets out there into the real world, there will be a lot of people trying to get it. We don’t want to have ‘Esketamines “R” Us’ clinics popping up everywhere.”

The FDA usually follows its panels’ recommendations, which are not binding.

[email protected]

ROCKVILLE, MD – If approved for treatment-resistant depression, intranasal esketamine will be strictly regulated in the clinic, with federal monitoring requirements designed to prevent misuse, abuse, or diversion of the drug.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Managed under a Food and Drug Administration Risk Evaluation and Mitigation Strategy (REMS), such a program would establish a stringent post-administration protocol of observation and blood pressure monitoring and require every provider – whether a large health care center or a single clinician – to obtain federal certification to dispense the medication.

At a joint meeting of FDA’s Psychopharmacologic Drugs Advisory and Drug Safety and Risk Management Advisory committees, some members offered a more tempered view while still supporting the approval pathway of the N-methyl-D-aspartate receptor antagonist. By a vote of 14-2, with one abstention, they agreed Feb. 12 that the benefits outweigh the risks of esketamine for treatment-resistant depression.

“I think it has the potential to be a game changer in treatment-resistant depression,” said Walter Dunn, MD, PhD, of the University of California, Los Angeles. “We may someday talk about 2019 in the same way we now talk about the late ’80s, when the first [selective serotonin reuptake inhibitors] were approved.”

Janssen Pharmaceuticals, which is developing the drug, incorporated concerns about misuse from the beginning. Even the delivery device is designed to prevent such issues, a company spokesman said.

• Prescriber training on the risks of esketamine and importance of monitoring patients after their dose is administered and the need to register patients
•  Administration of esketamine only in certain health care settings that ensure patient monitoring by a health care clinician for 2 hours after administration
•  Pharmacies, clinicians, or health care settings that dispense the drug are specially certified to ensure that esketamine is not dispensed directly to patients and that patients are monitored
•  Enrollment of patients who are treated with esketamine in a registry to better characterize the risks associated with esketamine administration and inform risk mitigation strategies

After administration, patients would be monitored for at least 2 hours for the common side effects, sedation and dissociation that typically clear within that time. Transient blood pressure fluctuations also can occur shortly after administration and would be monitored until stable. Patients should also be counseled not to drive the day of treatment, and to bring a companion along to drive them home.

Dr. Dunn, however, suggested that some facets of the proposed REMS might create unnecessary barriers for some patients and that stringent monitoring after every single dose – potentially for years – might not be necessary for everyone.

“The REM is certainly important to address the potential for diversion and misuse and adverse effects, but there needs to be a pathway to reduce monitoring requirements” on an individual basis. “If a patient is doing well for a year or so, in remission with no side effects, we should have a way to reduce the need for monitoring. If we make it too much of a burden to go in, get the medication, stay for a couple of hours for monitoring, it’s easy to skip a dose. And we know the number one predictor of relapse is medication nonadherence.”

The facility certification requirement also could curtail access to esketamine, said Steven B. Meisel, PharmD, of Minneapolis.

“How do we define a medically supervised center? Is it somewhere with a nurse onsite? A physician onsite? Does it have to have access to emergency services? This issue of access vs. control and safety is a very important one.”

He posed a clinical conundrum: A patient doing well on regular esketamine who wants to go on an extended trip. Under the proposed REMS, that patient would not be able to access his regular dose, which could only be handled, sorted, and administered by a certified health care clinician. “How are we going to deal with this? There will be great pressure to loosen this up in some manner. But if we allow a patient who’s been doing well on regular treatment with no relapse to have this at home, do we open the way for a teenager to take a bottle or two to a party? Those are real-world issues and must be considered when we establish a REM in a real world that demands access to needed therapy.”

Erring on the side of caution is the responsibility of policymakers, argued Kim Witczak, executive director of Woodymatters, a consumer-driven, nonprofit drug safety organization dedicated to FDA reform. Ms. Witczak was one of two dissenting voices on the vote.

“This has so much potential for so many people who just want a quick fix [for their mood disorders], and the marketing side will see this,” she predicted. “I would want to be very cautious. Once it gets out there into the real world, there will be a lot of people trying to get it. We don’t want to have ‘Esketamines “R” Us’ clinics popping up everywhere.”

The FDA usually follows its panels’ recommendations, which are not binding.

[email protected]

ROCKVILLE, MD – If approved for treatment-resistant depression, intranasal esketamine will be strictly regulated in the clinic, with federal monitoring requirements designed to prevent misuse, abuse, or diversion of the drug.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Managed under a Food and Drug Administration Risk Evaluation and Mitigation Strategy (REMS), such a program would establish a stringent post-administration protocol of observation and blood pressure monitoring and require every provider – whether a large health care center or a single clinician – to obtain federal certification to dispense the medication.

At a joint meeting of FDA’s Psychopharmacologic Drugs Advisory and Drug Safety and Risk Management Advisory committees, some members offered a more tempered view while still supporting the approval pathway of the N-methyl-D-aspartate receptor antagonist. By a vote of 14-2, with one abstention, they agreed Feb. 12 that the benefits outweigh the risks of esketamine for treatment-resistant depression.

“I think it has the potential to be a game changer in treatment-resistant depression,” said Walter Dunn, MD, PhD, of the University of California, Los Angeles. “We may someday talk about 2019 in the same way we now talk about the late ’80s, when the first [selective serotonin reuptake inhibitors] were approved.”

Janssen Pharmaceuticals, which is developing the drug, incorporated concerns about misuse from the beginning. Even the delivery device is designed to prevent such issues, a company spokesman said.

• Prescriber training on the risks of esketamine and importance of monitoring patients after their dose is administered and the need to register patients
•  Administration of esketamine only in certain health care settings that ensure patient monitoring by a health care clinician for 2 hours after administration
•  Pharmacies, clinicians, or health care settings that dispense the drug are specially certified to ensure that esketamine is not dispensed directly to patients and that patients are monitored
•  Enrollment of patients who are treated with esketamine in a registry to better characterize the risks associated with esketamine administration and inform risk mitigation strategies

After administration, patients would be monitored for at least 2 hours for the common side effects, sedation and dissociation that typically clear within that time. Transient blood pressure fluctuations also can occur shortly after administration and would be monitored until stable. Patients should also be counseled not to drive the day of treatment, and to bring a companion along to drive them home.

Dr. Dunn, however, suggested that some facets of the proposed REMS might create unnecessary barriers for some patients and that stringent monitoring after every single dose – potentially for years – might not be necessary for everyone.

“The REM is certainly important to address the potential for diversion and misuse and adverse effects, but there needs to be a pathway to reduce monitoring requirements” on an individual basis. “If a patient is doing well for a year or so, in remission with no side effects, we should have a way to reduce the need for monitoring. If we make it too much of a burden to go in, get the medication, stay for a couple of hours for monitoring, it’s easy to skip a dose. And we know the number one predictor of relapse is medication nonadherence.”

The facility certification requirement also could curtail access to esketamine, said Steven B. Meisel, PharmD, of Minneapolis.

“How do we define a medically supervised center? Is it somewhere with a nurse onsite? A physician onsite? Does it have to have access to emergency services? This issue of access vs. control and safety is a very important one.”

He posed a clinical conundrum: A patient doing well on regular esketamine who wants to go on an extended trip. Under the proposed REMS, that patient would not be able to access his regular dose, which could only be handled, sorted, and administered by a certified health care clinician. “How are we going to deal with this? There will be great pressure to loosen this up in some manner. But if we allow a patient who’s been doing well on regular treatment with no relapse to have this at home, do we open the way for a teenager to take a bottle or two to a party? Those are real-world issues and must be considered when we establish a REM in a real world that demands access to needed therapy.”

Erring on the side of caution is the responsibility of policymakers, argued Kim Witczak, executive director of Woodymatters, a consumer-driven, nonprofit drug safety organization dedicated to FDA reform. Ms. Witczak was one of two dissenting voices on the vote.

“This has so much potential for so many people who just want a quick fix [for their mood disorders], and the marketing side will see this,” she predicted. “I would want to be very cautious. Once it gets out there into the real world, there will be a lot of people trying to get it. We don’t want to have ‘Esketamines “R” Us’ clinics popping up everywhere.”

The FDA usually follows its panels’ recommendations, which are not binding.

[email protected]

A multicenter, randomized study comparing laparoscopic and robotic assisted surgical approaches is being conducted to examine outcomes for ventral hernia repairs.

In the trial precis, the researchers wrote, “The robotic platform in surgery is growing exponentially. Despite this, the evidence supporting robotics remains limited. Studies demonstrating benefit, such as improved outcomes or decreased hospital length of stay, are largely cohort studies subject to substantial bias. Among randomized controlled trials, none have demonstrated benefit with robotic surgery.”

Study participants will be randomized to two arms, one for laparoscopic hernia repair and the other for robotic repair. Patients in both arms will be treated with a mid-density polypropylene mesh with a one-sided adhesion barrier.

The primary outcomes studied are length of stay in the hospital and readmissions out to 90 days. Secondary outcomes include the occurrence of surgical-site infection, hematoma, seroma, dehiscence, necrosis, nonhealing wound, hernia recurrence, and several cost and quality-of-life measures.

Patients included must be over age 18 and undergoing elective ventral hernia repair deemed appropriate for minimally invasive repair. Exclusions include those unlikely to survive beyond 2 years based on surgeon judgment or are unlikely to follow up. In addition, patients are excluded if they have advanced COPD or heart failure, a history of open abdomen or extensive lysis of adhesions for bowel obstruction, ascites caused by cirrhosis or malignancy, active infection, or a large hernia larger than 12 cm. Estimated enrollment is 120 patients, and the researchers expect the study to end in 2023.

For more details on the study (NT03490266), go to clinicaltrials.gov.

A multicenter, randomized study comparing laparoscopic and robotic assisted surgical approaches is being conducted to examine outcomes for ventral hernia repairs.

In the trial precis, the researchers wrote, “The robotic platform in surgery is growing exponentially. Despite this, the evidence supporting robotics remains limited. Studies demonstrating benefit, such as improved outcomes or decreased hospital length of stay, are largely cohort studies subject to substantial bias. Among randomized controlled trials, none have demonstrated benefit with robotic surgery.”

Study participants will be randomized to two arms, one for laparoscopic hernia repair and the other for robotic repair. Patients in both arms will be treated with a mid-density polypropylene mesh with a one-sided adhesion barrier.

The primary outcomes studied are length of stay in the hospital and readmissions out to 90 days. Secondary outcomes include the occurrence of surgical-site infection, hematoma, seroma, dehiscence, necrosis, nonhealing wound, hernia recurrence, and several cost and quality-of-life measures.

Patients included must be over age 18 and undergoing elective ventral hernia repair deemed appropriate for minimally invasive repair. Exclusions include those unlikely to survive beyond 2 years based on surgeon judgment or are unlikely to follow up. In addition, patients are excluded if they have advanced COPD or heart failure, a history of open abdomen or extensive lysis of adhesions for bowel obstruction, ascites caused by cirrhosis or malignancy, active infection, or a large hernia larger than 12 cm. Estimated enrollment is 120 patients, and the researchers expect the study to end in 2023.

For more details on the study (NT03490266), go to clinicaltrials.gov.

A multicenter, randomized study comparing laparoscopic and robotic assisted surgical approaches is being conducted to examine outcomes for ventral hernia repairs.

In the trial precis, the researchers wrote, “The robotic platform in surgery is growing exponentially. Despite this, the evidence supporting robotics remains limited. Studies demonstrating benefit, such as improved outcomes or decreased hospital length of stay, are largely cohort studies subject to substantial bias. Among randomized controlled trials, none have demonstrated benefit with robotic surgery.”

Study participants will be randomized to two arms, one for laparoscopic hernia repair and the other for robotic repair. Patients in both arms will be treated with a mid-density polypropylene mesh with a one-sided adhesion barrier.

The primary outcomes studied are length of stay in the hospital and readmissions out to 90 days. Secondary outcomes include the occurrence of surgical-site infection, hematoma, seroma, dehiscence, necrosis, nonhealing wound, hernia recurrence, and several cost and quality-of-life measures.

Patients included must be over age 18 and undergoing elective ventral hernia repair deemed appropriate for minimally invasive repair. Exclusions include those unlikely to survive beyond 2 years based on surgeon judgment or are unlikely to follow up. In addition, patients are excluded if they have advanced COPD or heart failure, a history of open abdomen or extensive lysis of adhesions for bowel obstruction, ascites caused by cirrhosis or malignancy, active infection, or a large hernia larger than 12 cm. Estimated enrollment is 120 patients, and the researchers expect the study to end in 2023.

For more details on the study (NT03490266), go to clinicaltrials.gov.

HONOLULU – Vaccination against shingles or treating shingles with antiviral medication once it occurs does not alter the increased risk of acute ischemic stroke attributed to reactivated herpes zoster virus, according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.

The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.

Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.

Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.

To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.

IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).

One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.

The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.

The investigators reported no funding source or disclosures for this study.

[email protected]

SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39

HONOLULU – Vaccination against shingles or treating shingles with antiviral medication once it occurs does not alter the increased risk of acute ischemic stroke attributed to reactivated herpes zoster virus, according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.

The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.

Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.

Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.

To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.

IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).

One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.

The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.

The investigators reported no funding source or disclosures for this study.

[email protected]

SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39

HONOLULU – Vaccination against shingles or treating shingles with antiviral medication once it occurs does not alter the increased risk of acute ischemic stroke attributed to reactivated herpes zoster virus, according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.

The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.

Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.

Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.

To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.

IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).

One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.

The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.

The investigators reported no funding source or disclosures for this study.

[email protected]

SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39

Aspiration pneumonia refers to an infection of the lung parenchyma in an individual who has inhaled a bolus of endogenous flora that overwhelms the natural defenses of the respiratory system. It primarily affects older adults with almost 80% of cases occurring in those 65 years and older.¹ Compared with nonaspiration pneumonia, aspiration pneumonia (whether community acquired or healthcare associated) results in more ICU stays, mechanical ventilation, increased length of hospital stay, and higher mortality.²

The etiology of aspiration pneumonia comes from aspirated bacteria from the oropharynx or stomach.³ However, aspiration alone is a common occurrence and does not always lead to clinical pneumonia. Indeed, one study demonstrated that 45% of “normal subjects” aspirate in their sleep,⁴ illustrating that our bodies have evolved defense mechanisms to protect us from aspirated bacteria. Thus, it is only when these systems are overwhelmed, after compromise of both glottic closure and the cough reflex in addition to dysphagia,³ that an infection manifests.

Aspiration pneumonitis refers to a significant inflammation of the lung parenchyma that results from inhalation of regurgitated gastric contents.⁵ It can produce fever, cough, wheezing, shortness of breath, hypoxemia, leukocytosis, and a pulmonary infiltrate as well as lead to severe acute respiratory distress syndrome and even death. In the past, the use of antibiotics shortly after aspiration in patients who develop a fever, leukocytosis, or a pulmonary infiltrate was discouraged.⁵ Empiric antibiotics were recommended only for patients who aspirate gastric contents and who have conditions associated with colonization of gastric contents, such as small-bowel obstruction.⁵ Yet, it is difficult to distinguish aspiration pneumonitis from pneumonia⁶ and there are no randomized trials in older adults to help guide their management.

Pneumonia in older adults can present in an atypical fashion. In one study of community-acquired pneumonia (CAP), the combination of cough, fever, and dyspnea is present in only 31% of patients, although separately, they are present in 67%, 64%, and 71% of patients, respectively. The same study also showed that delirium was present in 45% of patients with CAP.⁷ Nonrespiratory symptoms were present during the initial presentation of CAP in 55% of patients, with confusion in 42%, and falls in 16% of cases.⁸ The same is true of aspiration pneumonia where altered mental status is seen in approximately 30% of community-acquired aspiration pneumonia (CAAP) patients and in 19% of continuing care facility patients with aspiration pneumonia.² Another study that compared CAP, CAAP, and healthcare-associated aspiration pneumonia (HCAAP) showed that confusion is present in 5.1%, 12.7%, and 18.6%, respectively.⁹ The absence of fever in older adults is shown in studies where fever, defined as greater than or equal to 37.5°C, is absent in 32% of the very old¹⁰and in 40% of patients 65 years or older when it was defined as greater than 37°C.⁸ The inconsistencies regarding typical symptoms of pneumonia in the older adult population are also confirmed in nursing home residents.¹¹ Ultimately, it is important to remember that any infection in older adults, especially in those residing in long-term care facilities, may present with subtle findings such as an acute change in cognitive and functional status.¹²

Risk Factors for Aspiration Pneumonia

Risk factors for aspiration pneumonia, while not universally agreed upon, are important to recognize as they increase the probability of the diagnosis when present. A 2011 systematic review identified age, male gender, lung disease, dysphagia, and diabetes mellitus (level 2a), as well as severe dementia, angiotensin I-converting enzyme deletion/deletion genotype, and poor oral health (level 2b) as risk factors.¹³ In 2016, a panel of experts reached a consensus (modified Delphi Method) on the following risk factors for the diagnosis of aspiration pneumonia in nursing home residents: history of dysphagia, choking incident, tube feeding, neurologic disease, and cognitive impairment. The presence of one or more of these risk factors in the appropriate clinical setting may suggest a diagnosis of aspiration pneumonia.¹⁴

Radiographic/Ultrasonographic Imaging

In the appropriate scenario, the diagnosis of aspiration pneumonia is supported with an image representative of pneumonia. The pulmonary segment involved in aspiration pneumonia depends on the position of the patient during the aspiration event. If the aspiration event occurs while the patient is in the recumbent position, development of pneumonia is more common in the posterior segments of the upper lobes and the apical segments of the lower lobes; whereas if it occurs while the patient is in an upright position, the location changes to the basal segments of the lower lobes.³

Overall, the sensitivity of a chest X-ray to diagnose pneumonia ranges between 32%-77.7%,^15-17 suggesting that a significant proportion of patients suspected of having pneumonia in past research studies, may have been misdiagnosed. Studies using lung ultrasound to identify pneumonia demonstrate a higher sensitivity, but additional research is needed to validate these findings.^17-19 Noncontrast CT scans of the chest remain the reference standard for diagnosing pneumonia and currently tend to have the largest impact on diagnosis and subsequent treatment decisions.^15,16,20,21 As a result, if radiation exposure risks are not a concern for the patient, we recommend utilizing noncontrast CT imaging whenever the diagnosis is in doubt until future research elucidates the most appropriate approach to imaging.

Diagnosis

Diagnosing aspiration pneumonia is difficult, in part because there is no universal definition or set of diagnostic criteria. The diagnosis of aspiration pneumonia is supported by the fulfillment of three criteria. First, appropriate risk factors for aspiration, as documented above, should be present. Second, there should be evidence of clinical signs and symptoms of pneumonia (typical or atypical). Third, radiographic representation of pneumonia in a dependent pulmonary segment confirms the diagnosis. Once these criteria are met, it is important to distinguish between CAAP and HCAAP with particular attention to risk factors for multidrug-resistant (MDR) organisms and Pseudomonas aeruginosa (PA).

Many studies have tried to determine the exact bacterial etiology of aspiration pneumonia as documented in the Table.

Even when an ideal method is used to obtain a good sample, however, the results are limited by other variables in the study. For example, in studies that use protected brush specimens and protected bronchoalveolar lavage to acquire samples for culture, many patients received antibiotics prior to sampling, and the studies are small (Table). Although anaerobes have traditionally been implicated in aspiration pneumonia, only El-Solh et al.²² were able to culture a significant proportion of anaerobes. The study, however, was limited to institutionalized older adults requiring mechanical ventilation and it did not require the typical radiographic location for aspiration pneumonia. Even under the best circumstances, it is difficult to determine causality because the antibiotics used to treat these cases of aspiration pneumonia cover a broad range of organisms. Based on the studies in the Table, causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods in addition to traditional organisms classically thought to cause aspiration pneumonia-anaerobes. Microbiologic etiology, however, may also be insinuated from the studies discussed in the therapeutic strategies section below as some include antibiotics with limited antimicrobial activity.

Therapeutic Strategies

The management of aspiration pneumonia has evolved significantly since it was first studied in the 1970s because of the development of antibiotic resistance patterns, newer antibiotics, and increasing information on the diversity of pathogens involved in each subset of aspiration syndromes. The antimicrobial treatment of aspiration pneumonia was classically directed against anaerobic pathogens; treatment of these infections, however, was extrapolated from studies of pulmonary abscesses and other anaerobic pulmonary infections.

A randomized controlled trial in the mid-1980s comparing penicillin and clindamycin demonstrated a significantly improved cure rate in the clindamycin group.²³ A follow-up study in 1990 implicated a significant number of penicillin-resistant Bacteroides infections—the majority of these infections were subsequently reclassified as Prevotella melaninogenica—as the cause for high rates of penicillin resistance in lung abscesses and necrotizing pneumonias, further supporting clindamycin as the treatment of choice for these infections.²⁴ Amoxicillin-clavulanic acid (IV and PO regimens), studied in the treatment of community-acquired necrotizing pneumonia/lung abscess, shows good efficacy as well.²⁵ This study also attempted to elucidate the underlying causative organisms in these patients. Organisms associated with CAP as well as anaerobic organisms were isolated, giving more credence to the idea of broader coverage for aspiration pneumonia.

Community-Acquired Aspiration Pneumonia/Healthcare-Associated Aspiration Pneumonia

The importance of making a diagnostic distinction between CAAP versus HCAAP is critical for management strategies. A prospective population-based study demonstrated that ICU length of stay and 30-day mortality is highest for HCAAP, followed by CAAP, and lastly for those with CAP.⁹ Although some studies use different nomenclature for identifying aspiration pneumonia patients at risk for a wider array of microorganisms, we attempt to standardize the language by using HCAAP. The literature on nonaspiration pneumonia is changing from terms such as CAP and healthcare-associated pneumonia (HCAP) to pneumonia with the risk of MDR organisms. One study proposed a new treatment algorithm for CAP based on the presence or absence of the following six risk factors: prior hospitalization of greater than or equal to two days in the preceding 90 days, immunosuppression, previous antibiotic use within the preceding 90 days, use of gastric acid-suppressive agents, tube feeding, and nonambulatory status.²⁶ A similar approach proposed years earlier for HCAP patients found the following to be risk factors for MDR organisms: hospitalization in the past 90 days, antibiotic therapy in the past six months, poor functional status as defined by activities of daily living score, and immune suppression.²⁷ Other factors, such as structural lung disease, that increase the risk of organisms resistant to standard antibiotic treatment regimens^28-31 should be considered in aspiration pneumonia as well. Aspiration pneumonia is following a similar trajectory where the risk of MDR organisms is taking precedence over the environment of acquisition. The final nomenclature will allow the healthcare provider to understand the organisms that need to be targeted when choosing an appropriate antibiotic treatment regimen.

There is evidence supporting the premise that CAAP and nursing home patients with no risk factors for MDR organisms can be treated with standard regimens used for patients with CAP. A prospective cohort study in 2014 did not show any statistically significant differences in clinical outcomes in nursing and healthcare-associated aspiration pneumonia patients (with no risks of MDR organisms) treated with azithromycin versus ampicillin/sulbactam. However, only 36 patients were included in the azithromycin arm, and the therapeutic choices were made by the treating physician.³²

A prospective study of 95 long-term care residents reported that of those patients admitted to the ICU with severe aspiration pneumonia, the causative organisms are gram-negative enteric bacilli in 49% of isolates, anaerobes in 16%, and Staphylococcus aureus in 12%.²² This study mentioned that six of seven anaerobic pneumonia cases had inadequate anaerobic coverage yet were effectively treated; based on the organisms represented, however, the antibiotics administered did provide some coverage.²² Prevotella was one of the common anaerobic organisms that could be treated by levofloxacin or ceftriaxone/azithromycin, possibly explaining the success of azithromycin in the study quoted previously.^22,32 Therefore, although anaerobic organisms still need to be considered, some may be treated by traditional CAP coverage.²²

In a 2005 randomized prospective study of 100 patients aged 71 to 94 years, clindamycin was found to have clinical efficacy equivalent to ampicillin-sulbactam and panipenem in the treatment of mild-to-moderate aspiration pneumonia.³³ Most patients in this study are nursing home residents, and 53% of sputum cultures in the clindamycin arm grew gram-negative rods. In contrast to the previous study, the significance of gram-negative rod infections in this population of patients, with less severe infections, is called into question, as clindamycin has no coverage against these organisms. This premise is supported by a more recent study using azithromycin in nursing and healthcare-associated aspiration pneumonia patients, mentioned previously.³² Taken together, these three studies suggest that the severity of aspiration pneumonia may be a risk factor that needs to be taken into account when considering broad-spectrum antimicrobial coverage.

While further research is needed to validate treatment approaches, based on the current literature we propose the following:

CAAP requiring hospitalization but without any of the following-risk for PA or MDR organisms, septic shock, the need for ICU admission, or mechanical ventilation-can be treated with standard CAP therapy that covers anaerobes.^26,32-34 Patients with CAAP and either of the following—risk factors for MDR organisms, septic shock, need for ICU admission, or mechanical ventilation—should be considered for broader coverage with vancomycin or linezolid, antipseudomonal antibiotics, and anaerobic coverage. CAAP with specific risk for a PA infection should be considered for two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic, and one has anaerobic coverage).

Severe HCAAP without risk for MDR organisms or PA but with any of the following-septic shock, ICU admission, or mechanical ventilation-can be treated based on the 2016 Infectious Diseases Society of America guideline recommendation for hospital-acquired pneumonia, with a regimen that also provides adequate anaerobic coverage.³⁵ If patients have HCAAP with one or more risk factors for MDR organisms, no septic shock, and no need for ICU admission or mechanical ventilation, provide coverage with a similar regimen. In contrast, HCAAP with risk factors for PA or severe HCAAP causing septic shock, requiring ICU admission, or needing mechanical ventilation, which occurs in the setting of one or more risk factors for MDR organisms, or structural lung disease, should receive two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic and one has anaerobic coverage) in addition to vancomycin or linezolid.

A recent systematic review demonstrates the paucity of studies of ideal methodologic design which complicates the ability to recommend, with confidence, one guideline-based antimicrobial regimen over another.³⁶ Future studies may determine that despite the severity of the infection, if patients do not carry any risk for MDR pathogens or PA, they may only require CAAP coverage. When a patient presents with an acute infection, it is prudent to review previous cultures, and although it may be necessary to treat with broad-spectrum antibiotics initially, it is always important to narrow the spectrum based on reliable culture results. If future studies support the results of many studies cited in this article, we may be using fewer antibiotics with narrower spectrums in the near future.

Prevention

Although the healthcare system has practices in place to prevent aspiration pneumonia, the evidence supporting them are either inconclusive or not of ideal methodological design. Two systematic reviews failed to show statistically significant decreases in rates of aspiration pneumonia or mortality using the standard of care positioning strategies or thickened fluids in patients with chronic dysphagia.^37,38 One study showed a decreased incidence of all pneumonia in dysphasic patients with dementia or Parkinson disease when a chin-down posture (with thin liquids) or thickened fluids in a head-neutral position was used. The study, however, has significant limitations, including a lack of a “no treatment” group for comparison, which did not allow investigators to conclude that the decreased incidence was from their interventions.³⁹

There are preventive strategies that show a decreased risk of aspiration pneumonia. Poor oral hygiene seems to be a modifiable risk factor to establish better control of oral flora and decrease aspiration pneumonia. A systematic review of five studies, evaluating the effects of oral healthcare on the incidence of aspiration pneumonia in frail older people, found that tooth brushing after each meal along with cleaning dentures once a day and professional oral healthcare once a week decreases febrile days, pneumonia, and dying from pneumonia.⁴⁰A two-year historical cohort study using aromatherapy with black pepper oil, followed by application of capsaicin troches, and finally menthol gel, as the first meal, leads to a decreased incidence of pneumonia and febrile days in older adults with dysphagia.⁴¹ Well-designed validation studies may establish these practices as the new standard of care for preventing pneumonia in patients with dysphagia.

Feeding Tubes

Multiple studies show that in older adults with advanced dementia there is no survival benefit from percutaneous endoscopic gastrostomy (PEG) tube placement^42-44 and more recent systematic reviews also conclude that there is currently no evidence to support the use of PEG tubes in this specific population.^45,46 In February 2013, as part of the American Board of Internal Medicine Foundation Choosing Wisely^® campaign, the American Geriatrics Society advised providers not to recommend percutaneous feeding tubes in patients with advanced dementia, rather, “offer assisted oral feeding.”⁴⁷ It is worth noting, however, that none of the studies reviewed were of ideal methodological design, so opinions may change with future studies.

A more recent study compared liquid feeds versus semisolid feeds in patients with PEG tubes. The study shows a 22.2% incidence of aspiration pneumonia in the liquid feed group, which is comparable to prior studies, but the incidence of aspiration pneumonia is only 2.2% in the semisolid feed group (P < .005).⁴⁸ A benefit of this size warrants future studies for validation.

Aspiration pneumonia leads to increased mortality when compared with CAP and HCAP.² Until future studies validate or refute the current understanding surrounding its management, the following should provide some guidance: aspiration pneumonia should be suspected in any individual with risk factors of aspiration who presents with typical or atypical symptoms of pneumonia. Confirmation of the diagnosis requires an image representative of pneumonia in the typical dependent lung segment on chest X-ray, lung ultrasound, or noncontrast CT scan of the chest. Treatment of aspiration pneumonia should take into account the site of acquisition, severity of illness, and risk for MDR organisms as the causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods, in addition to the traditional organisms classically thought to cause aspiration pneumonia-anaerobes.

Disclosures

The authors have nothing to disclose.

Aspiration pneumonia refers to an infection of the lung parenchyma in an individual who has inhaled a bolus of endogenous flora that overwhelms the natural defenses of the respiratory system. It primarily affects older adults with almost 80% of cases occurring in those 65 years and older.¹ Compared with nonaspiration pneumonia, aspiration pneumonia (whether community acquired or healthcare associated) results in more ICU stays, mechanical ventilation, increased length of hospital stay, and higher mortality.²

The etiology of aspiration pneumonia comes from aspirated bacteria from the oropharynx or stomach.³ However, aspiration alone is a common occurrence and does not always lead to clinical pneumonia. Indeed, one study demonstrated that 45% of “normal subjects” aspirate in their sleep,⁴ illustrating that our bodies have evolved defense mechanisms to protect us from aspirated bacteria. Thus, it is only when these systems are overwhelmed, after compromise of both glottic closure and the cough reflex in addition to dysphagia,³ that an infection manifests.

Aspiration pneumonitis refers to a significant inflammation of the lung parenchyma that results from inhalation of regurgitated gastric contents.⁵ It can produce fever, cough, wheezing, shortness of breath, hypoxemia, leukocytosis, and a pulmonary infiltrate as well as lead to severe acute respiratory distress syndrome and even death. In the past, the use of antibiotics shortly after aspiration in patients who develop a fever, leukocytosis, or a pulmonary infiltrate was discouraged.⁵ Empiric antibiotics were recommended only for patients who aspirate gastric contents and who have conditions associated with colonization of gastric contents, such as small-bowel obstruction.⁵ Yet, it is difficult to distinguish aspiration pneumonitis from pneumonia⁶ and there are no randomized trials in older adults to help guide their management.

Pneumonia in older adults can present in an atypical fashion. In one study of community-acquired pneumonia (CAP), the combination of cough, fever, and dyspnea is present in only 31% of patients, although separately, they are present in 67%, 64%, and 71% of patients, respectively. The same study also showed that delirium was present in 45% of patients with CAP.⁷ Nonrespiratory symptoms were present during the initial presentation of CAP in 55% of patients, with confusion in 42%, and falls in 16% of cases.⁸ The same is true of aspiration pneumonia where altered mental status is seen in approximately 30% of community-acquired aspiration pneumonia (CAAP) patients and in 19% of continuing care facility patients with aspiration pneumonia.² Another study that compared CAP, CAAP, and healthcare-associated aspiration pneumonia (HCAAP) showed that confusion is present in 5.1%, 12.7%, and 18.6%, respectively.⁹ The absence of fever in older adults is shown in studies where fever, defined as greater than or equal to 37.5°C, is absent in 32% of the very old¹⁰and in 40% of patients 65 years or older when it was defined as greater than 37°C.⁸ The inconsistencies regarding typical symptoms of pneumonia in the older adult population are also confirmed in nursing home residents.¹¹ Ultimately, it is important to remember that any infection in older adults, especially in those residing in long-term care facilities, may present with subtle findings such as an acute change in cognitive and functional status.¹²

Risk Factors for Aspiration Pneumonia

Risk factors for aspiration pneumonia, while not universally agreed upon, are important to recognize as they increase the probability of the diagnosis when present. A 2011 systematic review identified age, male gender, lung disease, dysphagia, and diabetes mellitus (level 2a), as well as severe dementia, angiotensin I-converting enzyme deletion/deletion genotype, and poor oral health (level 2b) as risk factors.¹³ In 2016, a panel of experts reached a consensus (modified Delphi Method) on the following risk factors for the diagnosis of aspiration pneumonia in nursing home residents: history of dysphagia, choking incident, tube feeding, neurologic disease, and cognitive impairment. The presence of one or more of these risk factors in the appropriate clinical setting may suggest a diagnosis of aspiration pneumonia.¹⁴

Radiographic/Ultrasonographic Imaging

In the appropriate scenario, the diagnosis of aspiration pneumonia is supported with an image representative of pneumonia. The pulmonary segment involved in aspiration pneumonia depends on the position of the patient during the aspiration event. If the aspiration event occurs while the patient is in the recumbent position, development of pneumonia is more common in the posterior segments of the upper lobes and the apical segments of the lower lobes; whereas if it occurs while the patient is in an upright position, the location changes to the basal segments of the lower lobes.³

Overall, the sensitivity of a chest X-ray to diagnose pneumonia ranges between 32%-77.7%,^15-17 suggesting that a significant proportion of patients suspected of having pneumonia in past research studies, may have been misdiagnosed. Studies using lung ultrasound to identify pneumonia demonstrate a higher sensitivity, but additional research is needed to validate these findings.^17-19 Noncontrast CT scans of the chest remain the reference standard for diagnosing pneumonia and currently tend to have the largest impact on diagnosis and subsequent treatment decisions.^15,16,20,21 As a result, if radiation exposure risks are not a concern for the patient, we recommend utilizing noncontrast CT imaging whenever the diagnosis is in doubt until future research elucidates the most appropriate approach to imaging.

Diagnosis

Diagnosing aspiration pneumonia is difficult, in part because there is no universal definition or set of diagnostic criteria. The diagnosis of aspiration pneumonia is supported by the fulfillment of three criteria. First, appropriate risk factors for aspiration, as documented above, should be present. Second, there should be evidence of clinical signs and symptoms of pneumonia (typical or atypical). Third, radiographic representation of pneumonia in a dependent pulmonary segment confirms the diagnosis. Once these criteria are met, it is important to distinguish between CAAP and HCAAP with particular attention to risk factors for multidrug-resistant (MDR) organisms and Pseudomonas aeruginosa (PA).

Many studies have tried to determine the exact bacterial etiology of aspiration pneumonia as documented in the Table.

Even when an ideal method is used to obtain a good sample, however, the results are limited by other variables in the study. For example, in studies that use protected brush specimens and protected bronchoalveolar lavage to acquire samples for culture, many patients received antibiotics prior to sampling, and the studies are small (Table). Although anaerobes have traditionally been implicated in aspiration pneumonia, only El-Solh et al.²² were able to culture a significant proportion of anaerobes. The study, however, was limited to institutionalized older adults requiring mechanical ventilation and it did not require the typical radiographic location for aspiration pneumonia. Even under the best circumstances, it is difficult to determine causality because the antibiotics used to treat these cases of aspiration pneumonia cover a broad range of organisms. Based on the studies in the Table, causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods in addition to traditional organisms classically thought to cause aspiration pneumonia-anaerobes. Microbiologic etiology, however, may also be insinuated from the studies discussed in the therapeutic strategies section below as some include antibiotics with limited antimicrobial activity.

Therapeutic Strategies

The management of aspiration pneumonia has evolved significantly since it was first studied in the 1970s because of the development of antibiotic resistance patterns, newer antibiotics, and increasing information on the diversity of pathogens involved in each subset of aspiration syndromes. The antimicrobial treatment of aspiration pneumonia was classically directed against anaerobic pathogens; treatment of these infections, however, was extrapolated from studies of pulmonary abscesses and other anaerobic pulmonary infections.

A randomized controlled trial in the mid-1980s comparing penicillin and clindamycin demonstrated a significantly improved cure rate in the clindamycin group.²³ A follow-up study in 1990 implicated a significant number of penicillin-resistant Bacteroides infections—the majority of these infections were subsequently reclassified as Prevotella melaninogenica—as the cause for high rates of penicillin resistance in lung abscesses and necrotizing pneumonias, further supporting clindamycin as the treatment of choice for these infections.²⁴ Amoxicillin-clavulanic acid (IV and PO regimens), studied in the treatment of community-acquired necrotizing pneumonia/lung abscess, shows good efficacy as well.²⁵ This study also attempted to elucidate the underlying causative organisms in these patients. Organisms associated with CAP as well as anaerobic organisms were isolated, giving more credence to the idea of broader coverage for aspiration pneumonia.

Community-Acquired Aspiration Pneumonia/Healthcare-Associated Aspiration Pneumonia

The importance of making a diagnostic distinction between CAAP versus HCAAP is critical for management strategies. A prospective population-based study demonstrated that ICU length of stay and 30-day mortality is highest for HCAAP, followed by CAAP, and lastly for those with CAP.⁹ Although some studies use different nomenclature for identifying aspiration pneumonia patients at risk for a wider array of microorganisms, we attempt to standardize the language by using HCAAP. The literature on nonaspiration pneumonia is changing from terms such as CAP and healthcare-associated pneumonia (HCAP) to pneumonia with the risk of MDR organisms. One study proposed a new treatment algorithm for CAP based on the presence or absence of the following six risk factors: prior hospitalization of greater than or equal to two days in the preceding 90 days, immunosuppression, previous antibiotic use within the preceding 90 days, use of gastric acid-suppressive agents, tube feeding, and nonambulatory status.²⁶ A similar approach proposed years earlier for HCAP patients found the following to be risk factors for MDR organisms: hospitalization in the past 90 days, antibiotic therapy in the past six months, poor functional status as defined by activities of daily living score, and immune suppression.²⁷ Other factors, such as structural lung disease, that increase the risk of organisms resistant to standard antibiotic treatment regimens^28-31 should be considered in aspiration pneumonia as well. Aspiration pneumonia is following a similar trajectory where the risk of MDR organisms is taking precedence over the environment of acquisition. The final nomenclature will allow the healthcare provider to understand the organisms that need to be targeted when choosing an appropriate antibiotic treatment regimen.

There is evidence supporting the premise that CAAP and nursing home patients with no risk factors for MDR organisms can be treated with standard regimens used for patients with CAP. A prospective cohort study in 2014 did not show any statistically significant differences in clinical outcomes in nursing and healthcare-associated aspiration pneumonia patients (with no risks of MDR organisms) treated with azithromycin versus ampicillin/sulbactam. However, only 36 patients were included in the azithromycin arm, and the therapeutic choices were made by the treating physician.³²

A prospective study of 95 long-term care residents reported that of those patients admitted to the ICU with severe aspiration pneumonia, the causative organisms are gram-negative enteric bacilli in 49% of isolates, anaerobes in 16%, and Staphylococcus aureus in 12%.²² This study mentioned that six of seven anaerobic pneumonia cases had inadequate anaerobic coverage yet were effectively treated; based on the organisms represented, however, the antibiotics administered did provide some coverage.²² Prevotella was one of the common anaerobic organisms that could be treated by levofloxacin or ceftriaxone/azithromycin, possibly explaining the success of azithromycin in the study quoted previously.^22,32 Therefore, although anaerobic organisms still need to be considered, some may be treated by traditional CAP coverage.²²

In a 2005 randomized prospective study of 100 patients aged 71 to 94 years, clindamycin was found to have clinical efficacy equivalent to ampicillin-sulbactam and panipenem in the treatment of mild-to-moderate aspiration pneumonia.³³ Most patients in this study are nursing home residents, and 53% of sputum cultures in the clindamycin arm grew gram-negative rods. In contrast to the previous study, the significance of gram-negative rod infections in this population of patients, with less severe infections, is called into question, as clindamycin has no coverage against these organisms. This premise is supported by a more recent study using azithromycin in nursing and healthcare-associated aspiration pneumonia patients, mentioned previously.³² Taken together, these three studies suggest that the severity of aspiration pneumonia may be a risk factor that needs to be taken into account when considering broad-spectrum antimicrobial coverage.

While further research is needed to validate treatment approaches, based on the current literature we propose the following:

CAAP requiring hospitalization but without any of the following-risk for PA or MDR organisms, septic shock, the need for ICU admission, or mechanical ventilation-can be treated with standard CAP therapy that covers anaerobes.^26,32-34 Patients with CAAP and either of the following—risk factors for MDR organisms, septic shock, need for ICU admission, or mechanical ventilation—should be considered for broader coverage with vancomycin or linezolid, antipseudomonal antibiotics, and anaerobic coverage. CAAP with specific risk for a PA infection should be considered for two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic, and one has anaerobic coverage).

Severe HCAAP without risk for MDR organisms or PA but with any of the following-septic shock, ICU admission, or mechanical ventilation-can be treated based on the 2016 Infectious Diseases Society of America guideline recommendation for hospital-acquired pneumonia, with a regimen that also provides adequate anaerobic coverage.³⁵ If patients have HCAAP with one or more risk factors for MDR organisms, no septic shock, and no need for ICU admission or mechanical ventilation, provide coverage with a similar regimen. In contrast, HCAAP with risk factors for PA or severe HCAAP causing septic shock, requiring ICU admission, or needing mechanical ventilation, which occurs in the setting of one or more risk factors for MDR organisms, or structural lung disease, should receive two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic and one has anaerobic coverage) in addition to vancomycin or linezolid.

A recent systematic review demonstrates the paucity of studies of ideal methodologic design which complicates the ability to recommend, with confidence, one guideline-based antimicrobial regimen over another.³⁶ Future studies may determine that despite the severity of the infection, if patients do not carry any risk for MDR pathogens or PA, they may only require CAAP coverage. When a patient presents with an acute infection, it is prudent to review previous cultures, and although it may be necessary to treat with broad-spectrum antibiotics initially, it is always important to narrow the spectrum based on reliable culture results. If future studies support the results of many studies cited in this article, we may be using fewer antibiotics with narrower spectrums in the near future.

Prevention

Although the healthcare system has practices in place to prevent aspiration pneumonia, the evidence supporting them are either inconclusive or not of ideal methodological design. Two systematic reviews failed to show statistically significant decreases in rates of aspiration pneumonia or mortality using the standard of care positioning strategies or thickened fluids in patients with chronic dysphagia.^37,38 One study showed a decreased incidence of all pneumonia in dysphasic patients with dementia or Parkinson disease when a chin-down posture (with thin liquids) or thickened fluids in a head-neutral position was used. The study, however, has significant limitations, including a lack of a “no treatment” group for comparison, which did not allow investigators to conclude that the decreased incidence was from their interventions.³⁹

There are preventive strategies that show a decreased risk of aspiration pneumonia. Poor oral hygiene seems to be a modifiable risk factor to establish better control of oral flora and decrease aspiration pneumonia. A systematic review of five studies, evaluating the effects of oral healthcare on the incidence of aspiration pneumonia in frail older people, found that tooth brushing after each meal along with cleaning dentures once a day and professional oral healthcare once a week decreases febrile days, pneumonia, and dying from pneumonia.⁴⁰A two-year historical cohort study using aromatherapy with black pepper oil, followed by application of capsaicin troches, and finally menthol gel, as the first meal, leads to a decreased incidence of pneumonia and febrile days in older adults with dysphagia.⁴¹ Well-designed validation studies may establish these practices as the new standard of care for preventing pneumonia in patients with dysphagia.

Feeding Tubes

Multiple studies show that in older adults with advanced dementia there is no survival benefit from percutaneous endoscopic gastrostomy (PEG) tube placement^42-44 and more recent systematic reviews also conclude that there is currently no evidence to support the use of PEG tubes in this specific population.^45,46 In February 2013, as part of the American Board of Internal Medicine Foundation Choosing Wisely^® campaign, the American Geriatrics Society advised providers not to recommend percutaneous feeding tubes in patients with advanced dementia, rather, “offer assisted oral feeding.”⁴⁷ It is worth noting, however, that none of the studies reviewed were of ideal methodological design, so opinions may change with future studies.

A more recent study compared liquid feeds versus semisolid feeds in patients with PEG tubes. The study shows a 22.2% incidence of aspiration pneumonia in the liquid feed group, which is comparable to prior studies, but the incidence of aspiration pneumonia is only 2.2% in the semisolid feed group (P < .005).⁴⁸ A benefit of this size warrants future studies for validation.

Aspiration pneumonia leads to increased mortality when compared with CAP and HCAP.² Until future studies validate or refute the current understanding surrounding its management, the following should provide some guidance: aspiration pneumonia should be suspected in any individual with risk factors of aspiration who presents with typical or atypical symptoms of pneumonia. Confirmation of the diagnosis requires an image representative of pneumonia in the typical dependent lung segment on chest X-ray, lung ultrasound, or noncontrast CT scan of the chest. Treatment of aspiration pneumonia should take into account the site of acquisition, severity of illness, and risk for MDR organisms as the causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods, in addition to the traditional organisms classically thought to cause aspiration pneumonia-anaerobes.

Disclosures

The authors have nothing to disclose.

Aspiration pneumonia refers to an infection of the lung parenchyma in an individual who has inhaled a bolus of endogenous flora that overwhelms the natural defenses of the respiratory system. It primarily affects older adults with almost 80% of cases occurring in those 65 years and older.¹ Compared with nonaspiration pneumonia, aspiration pneumonia (whether community acquired or healthcare associated) results in more ICU stays, mechanical ventilation, increased length of hospital stay, and higher mortality.²

The etiology of aspiration pneumonia comes from aspirated bacteria from the oropharynx or stomach.³ However, aspiration alone is a common occurrence and does not always lead to clinical pneumonia. Indeed, one study demonstrated that 45% of “normal subjects” aspirate in their sleep,⁴ illustrating that our bodies have evolved defense mechanisms to protect us from aspirated bacteria. Thus, it is only when these systems are overwhelmed, after compromise of both glottic closure and the cough reflex in addition to dysphagia,³ that an infection manifests.

Aspiration pneumonitis refers to a significant inflammation of the lung parenchyma that results from inhalation of regurgitated gastric contents.⁵ It can produce fever, cough, wheezing, shortness of breath, hypoxemia, leukocytosis, and a pulmonary infiltrate as well as lead to severe acute respiratory distress syndrome and even death. In the past, the use of antibiotics shortly after aspiration in patients who develop a fever, leukocytosis, or a pulmonary infiltrate was discouraged.⁵ Empiric antibiotics were recommended only for patients who aspirate gastric contents and who have conditions associated with colonization of gastric contents, such as small-bowel obstruction.⁵ Yet, it is difficult to distinguish aspiration pneumonitis from pneumonia⁶ and there are no randomized trials in older adults to help guide their management.

Pneumonia in older adults can present in an atypical fashion. In one study of community-acquired pneumonia (CAP), the combination of cough, fever, and dyspnea is present in only 31% of patients, although separately, they are present in 67%, 64%, and 71% of patients, respectively. The same study also showed that delirium was present in 45% of patients with CAP.⁷ Nonrespiratory symptoms were present during the initial presentation of CAP in 55% of patients, with confusion in 42%, and falls in 16% of cases.⁸ The same is true of aspiration pneumonia where altered mental status is seen in approximately 30% of community-acquired aspiration pneumonia (CAAP) patients and in 19% of continuing care facility patients with aspiration pneumonia.² Another study that compared CAP, CAAP, and healthcare-associated aspiration pneumonia (HCAAP) showed that confusion is present in 5.1%, 12.7%, and 18.6%, respectively.⁹ The absence of fever in older adults is shown in studies where fever, defined as greater than or equal to 37.5°C, is absent in 32% of the very old¹⁰and in 40% of patients 65 years or older when it was defined as greater than 37°C.⁸ The inconsistencies regarding typical symptoms of pneumonia in the older adult population are also confirmed in nursing home residents.¹¹ Ultimately, it is important to remember that any infection in older adults, especially in those residing in long-term care facilities, may present with subtle findings such as an acute change in cognitive and functional status.¹²

Risk Factors for Aspiration Pneumonia

Risk factors for aspiration pneumonia, while not universally agreed upon, are important to recognize as they increase the probability of the diagnosis when present. A 2011 systematic review identified age, male gender, lung disease, dysphagia, and diabetes mellitus (level 2a), as well as severe dementia, angiotensin I-converting enzyme deletion/deletion genotype, and poor oral health (level 2b) as risk factors.¹³ In 2016, a panel of experts reached a consensus (modified Delphi Method) on the following risk factors for the diagnosis of aspiration pneumonia in nursing home residents: history of dysphagia, choking incident, tube feeding, neurologic disease, and cognitive impairment. The presence of one or more of these risk factors in the appropriate clinical setting may suggest a diagnosis of aspiration pneumonia.¹⁴

Radiographic/Ultrasonographic Imaging

In the appropriate scenario, the diagnosis of aspiration pneumonia is supported with an image representative of pneumonia. The pulmonary segment involved in aspiration pneumonia depends on the position of the patient during the aspiration event. If the aspiration event occurs while the patient is in the recumbent position, development of pneumonia is more common in the posterior segments of the upper lobes and the apical segments of the lower lobes; whereas if it occurs while the patient is in an upright position, the location changes to the basal segments of the lower lobes.³

Overall, the sensitivity of a chest X-ray to diagnose pneumonia ranges between 32%-77.7%,^15-17 suggesting that a significant proportion of patients suspected of having pneumonia in past research studies, may have been misdiagnosed. Studies using lung ultrasound to identify pneumonia demonstrate a higher sensitivity, but additional research is needed to validate these findings.^17-19 Noncontrast CT scans of the chest remain the reference standard for diagnosing pneumonia and currently tend to have the largest impact on diagnosis and subsequent treatment decisions.^15,16,20,21 As a result, if radiation exposure risks are not a concern for the patient, we recommend utilizing noncontrast CT imaging whenever the diagnosis is in doubt until future research elucidates the most appropriate approach to imaging.

Diagnosis

Diagnosing aspiration pneumonia is difficult, in part because there is no universal definition or set of diagnostic criteria. The diagnosis of aspiration pneumonia is supported by the fulfillment of three criteria. First, appropriate risk factors for aspiration, as documented above, should be present. Second, there should be evidence of clinical signs and symptoms of pneumonia (typical or atypical). Third, radiographic representation of pneumonia in a dependent pulmonary segment confirms the diagnosis. Once these criteria are met, it is important to distinguish between CAAP and HCAAP with particular attention to risk factors for multidrug-resistant (MDR) organisms and Pseudomonas aeruginosa (PA).

Many studies have tried to determine the exact bacterial etiology of aspiration pneumonia as documented in the Table.

Even when an ideal method is used to obtain a good sample, however, the results are limited by other variables in the study. For example, in studies that use protected brush specimens and protected bronchoalveolar lavage to acquire samples for culture, many patients received antibiotics prior to sampling, and the studies are small (Table). Although anaerobes have traditionally been implicated in aspiration pneumonia, only El-Solh et al.²² were able to culture a significant proportion of anaerobes. The study, however, was limited to institutionalized older adults requiring mechanical ventilation and it did not require the typical radiographic location for aspiration pneumonia. Even under the best circumstances, it is difficult to determine causality because the antibiotics used to treat these cases of aspiration pneumonia cover a broad range of organisms. Based on the studies in the Table, causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods in addition to traditional organisms classically thought to cause aspiration pneumonia-anaerobes. Microbiologic etiology, however, may also be insinuated from the studies discussed in the therapeutic strategies section below as some include antibiotics with limited antimicrobial activity.

Therapeutic Strategies

The management of aspiration pneumonia has evolved significantly since it was first studied in the 1970s because of the development of antibiotic resistance patterns, newer antibiotics, and increasing information on the diversity of pathogens involved in each subset of aspiration syndromes. The antimicrobial treatment of aspiration pneumonia was classically directed against anaerobic pathogens; treatment of these infections, however, was extrapolated from studies of pulmonary abscesses and other anaerobic pulmonary infections.

A randomized controlled trial in the mid-1980s comparing penicillin and clindamycin demonstrated a significantly improved cure rate in the clindamycin group.²³ A follow-up study in 1990 implicated a significant number of penicillin-resistant Bacteroides infections—the majority of these infections were subsequently reclassified as Prevotella melaninogenica—as the cause for high rates of penicillin resistance in lung abscesses and necrotizing pneumonias, further supporting clindamycin as the treatment of choice for these infections.²⁴ Amoxicillin-clavulanic acid (IV and PO regimens), studied in the treatment of community-acquired necrotizing pneumonia/lung abscess, shows good efficacy as well.²⁵ This study also attempted to elucidate the underlying causative organisms in these patients. Organisms associated with CAP as well as anaerobic organisms were isolated, giving more credence to the idea of broader coverage for aspiration pneumonia.

Community-Acquired Aspiration Pneumonia/Healthcare-Associated Aspiration Pneumonia

The importance of making a diagnostic distinction between CAAP versus HCAAP is critical for management strategies. A prospective population-based study demonstrated that ICU length of stay and 30-day mortality is highest for HCAAP, followed by CAAP, and lastly for those with CAP.⁹ Although some studies use different nomenclature for identifying aspiration pneumonia patients at risk for a wider array of microorganisms, we attempt to standardize the language by using HCAAP. The literature on nonaspiration pneumonia is changing from terms such as CAP and healthcare-associated pneumonia (HCAP) to pneumonia with the risk of MDR organisms. One study proposed a new treatment algorithm for CAP based on the presence or absence of the following six risk factors: prior hospitalization of greater than or equal to two days in the preceding 90 days, immunosuppression, previous antibiotic use within the preceding 90 days, use of gastric acid-suppressive agents, tube feeding, and nonambulatory status.²⁶ A similar approach proposed years earlier for HCAP patients found the following to be risk factors for MDR organisms: hospitalization in the past 90 days, antibiotic therapy in the past six months, poor functional status as defined by activities of daily living score, and immune suppression.²⁷ Other factors, such as structural lung disease, that increase the risk of organisms resistant to standard antibiotic treatment regimens^28-31 should be considered in aspiration pneumonia as well. Aspiration pneumonia is following a similar trajectory where the risk of MDR organisms is taking precedence over the environment of acquisition. The final nomenclature will allow the healthcare provider to understand the organisms that need to be targeted when choosing an appropriate antibiotic treatment regimen.

There is evidence supporting the premise that CAAP and nursing home patients with no risk factors for MDR organisms can be treated with standard regimens used for patients with CAP. A prospective cohort study in 2014 did not show any statistically significant differences in clinical outcomes in nursing and healthcare-associated aspiration pneumonia patients (with no risks of MDR organisms) treated with azithromycin versus ampicillin/sulbactam. However, only 36 patients were included in the azithromycin arm, and the therapeutic choices were made by the treating physician.³²

A prospective study of 95 long-term care residents reported that of those patients admitted to the ICU with severe aspiration pneumonia, the causative organisms are gram-negative enteric bacilli in 49% of isolates, anaerobes in 16%, and Staphylococcus aureus in 12%.²² This study mentioned that six of seven anaerobic pneumonia cases had inadequate anaerobic coverage yet were effectively treated; based on the organisms represented, however, the antibiotics administered did provide some coverage.²² Prevotella was one of the common anaerobic organisms that could be treated by levofloxacin or ceftriaxone/azithromycin, possibly explaining the success of azithromycin in the study quoted previously.^22,32 Therefore, although anaerobic organisms still need to be considered, some may be treated by traditional CAP coverage.²²

In a 2005 randomized prospective study of 100 patients aged 71 to 94 years, clindamycin was found to have clinical efficacy equivalent to ampicillin-sulbactam and panipenem in the treatment of mild-to-moderate aspiration pneumonia.³³ Most patients in this study are nursing home residents, and 53% of sputum cultures in the clindamycin arm grew gram-negative rods. In contrast to the previous study, the significance of gram-negative rod infections in this population of patients, with less severe infections, is called into question, as clindamycin has no coverage against these organisms. This premise is supported by a more recent study using azithromycin in nursing and healthcare-associated aspiration pneumonia patients, mentioned previously.³² Taken together, these three studies suggest that the severity of aspiration pneumonia may be a risk factor that needs to be taken into account when considering broad-spectrum antimicrobial coverage.

While further research is needed to validate treatment approaches, based on the current literature we propose the following:

CAAP requiring hospitalization but without any of the following-risk for PA or MDR organisms, septic shock, the need for ICU admission, or mechanical ventilation-can be treated with standard CAP therapy that covers anaerobes.^26,32-34 Patients with CAAP and either of the following—risk factors for MDR organisms, septic shock, need for ICU admission, or mechanical ventilation—should be considered for broader coverage with vancomycin or linezolid, antipseudomonal antibiotics, and anaerobic coverage. CAAP with specific risk for a PA infection should be considered for two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic, and one has anaerobic coverage).

Severe HCAAP without risk for MDR organisms or PA but with any of the following-septic shock, ICU admission, or mechanical ventilation-can be treated based on the 2016 Infectious Diseases Society of America guideline recommendation for hospital-acquired pneumonia, with a regimen that also provides adequate anaerobic coverage.³⁵ If patients have HCAAP with one or more risk factors for MDR organisms, no septic shock, and no need for ICU admission or mechanical ventilation, provide coverage with a similar regimen. In contrast, HCAAP with risk factors for PA or severe HCAAP causing septic shock, requiring ICU admission, or needing mechanical ventilation, which occurs in the setting of one or more risk factors for MDR organisms, or structural lung disease, should receive two antipseudomonal antibiotics (where only one can be a beta-lactam antibiotic and one has anaerobic coverage) in addition to vancomycin or linezolid.

A recent systematic review demonstrates the paucity of studies of ideal methodologic design which complicates the ability to recommend, with confidence, one guideline-based antimicrobial regimen over another.³⁶ Future studies may determine that despite the severity of the infection, if patients do not carry any risk for MDR pathogens or PA, they may only require CAAP coverage. When a patient presents with an acute infection, it is prudent to review previous cultures, and although it may be necessary to treat with broad-spectrum antibiotics initially, it is always important to narrow the spectrum based on reliable culture results. If future studies support the results of many studies cited in this article, we may be using fewer antibiotics with narrower spectrums in the near future.

Prevention

Although the healthcare system has practices in place to prevent aspiration pneumonia, the evidence supporting them are either inconclusive or not of ideal methodological design. Two systematic reviews failed to show statistically significant decreases in rates of aspiration pneumonia or mortality using the standard of care positioning strategies or thickened fluids in patients with chronic dysphagia.^37,38 One study showed a decreased incidence of all pneumonia in dysphasic patients with dementia or Parkinson disease when a chin-down posture (with thin liquids) or thickened fluids in a head-neutral position was used. The study, however, has significant limitations, including a lack of a “no treatment” group for comparison, which did not allow investigators to conclude that the decreased incidence was from their interventions.³⁹

There are preventive strategies that show a decreased risk of aspiration pneumonia. Poor oral hygiene seems to be a modifiable risk factor to establish better control of oral flora and decrease aspiration pneumonia. A systematic review of five studies, evaluating the effects of oral healthcare on the incidence of aspiration pneumonia in frail older people, found that tooth brushing after each meal along with cleaning dentures once a day and professional oral healthcare once a week decreases febrile days, pneumonia, and dying from pneumonia.⁴⁰A two-year historical cohort study using aromatherapy with black pepper oil, followed by application of capsaicin troches, and finally menthol gel, as the first meal, leads to a decreased incidence of pneumonia and febrile days in older adults with dysphagia.⁴¹ Well-designed validation studies may establish these practices as the new standard of care for preventing pneumonia in patients with dysphagia.

Feeding Tubes

Multiple studies show that in older adults with advanced dementia there is no survival benefit from percutaneous endoscopic gastrostomy (PEG) tube placement^42-44 and more recent systematic reviews also conclude that there is currently no evidence to support the use of PEG tubes in this specific population.^45,46 In February 2013, as part of the American Board of Internal Medicine Foundation Choosing Wisely^® campaign, the American Geriatrics Society advised providers not to recommend percutaneous feeding tubes in patients with advanced dementia, rather, “offer assisted oral feeding.”⁴⁷ It is worth noting, however, that none of the studies reviewed were of ideal methodological design, so opinions may change with future studies.

A more recent study compared liquid feeds versus semisolid feeds in patients with PEG tubes. The study shows a 22.2% incidence of aspiration pneumonia in the liquid feed group, which is comparable to prior studies, but the incidence of aspiration pneumonia is only 2.2% in the semisolid feed group (P < .005).⁴⁸ A benefit of this size warrants future studies for validation.

Aspiration pneumonia leads to increased mortality when compared with CAP and HCAP.² Until future studies validate or refute the current understanding surrounding its management, the following should provide some guidance: aspiration pneumonia should be suspected in any individual with risk factors of aspiration who presents with typical or atypical symptoms of pneumonia. Confirmation of the diagnosis requires an image representative of pneumonia in the typical dependent lung segment on chest X-ray, lung ultrasound, or noncontrast CT scan of the chest. Treatment of aspiration pneumonia should take into account the site of acquisition, severity of illness, and risk for MDR organisms as the causative organisms may include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and gram-negative rods, in addition to the traditional organisms classically thought to cause aspiration pneumonia-anaerobes.

Disclosures

The authors have nothing to disclose.

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).

JackF/thinkstockphotos.com

The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.

A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.

When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m² and higher.

“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.

In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.

Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B₆, vitamin B₁₂, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.

In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.

After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.

For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).

When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.

Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.

However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.

The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.

Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.

Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.

The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.

“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.

One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.

[email protected]

SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.

Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).

JackF/thinkstockphotos.com

The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.

A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.

When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m² and higher.

“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.

In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.

Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B₆, vitamin B₁₂, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.

In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.

After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.

For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).

When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.

Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.

However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.

The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.

Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.

Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.

The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.

“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.

One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.

[email protected]

SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.

Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).

JackF/thinkstockphotos.com

The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.

A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.

When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m² and higher.

“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.

In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.

Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B₆, vitamin B₁₂, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.

In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.

After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.

For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).

When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.

Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.

However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.

The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.

Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.

Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.

The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.

“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.

One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.

[email protected]

SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.

I have the unfortunate task of trying to teach medical students about psychiatry. I say “unfortunate,” as most of them find psychiatry a difficult art to understand, and they seem reluctant to classify psychiatry as a branch of medicine.

Wavebreakmedia/Thinkstock

In my efforts to keep things simple, I tell that them psychiatry is one of the most difficult branches of medicine as there are very few objective measures we can rely on to make sense of people’s behavior. Regrettably, the American Psychiatric Association’s Diagnostic and Statistical Manual only seems to confuse them more. So, I remind them that, in medicine, 90%-95% of diagnoses can be obtained from doing a good history, and, if we are lucky a drug level will show drugs in the system, a CT scan without contrast will show cerebral atrophy, or there will be a lab result that will be abnormal and point to a diagnosis. But mostly what they will be seeing is unusual behavior they are unable to classify.

So I try to make psychiatric diagnosis more manageable for them by telling them there are essentially five overarching categories of psychiatric illness: identifiable brain damage, psychosis, affective disorders, anxiety disorders, and personality disorders. Under the brain damage category, I include the short- and long-term effects of drugs, major neurocognitive disorders (called dementia before DSM-5), cerebrovascular infarcts, traumatic brain injury, and neurodevelopmental disorders. For their exams and, if they are interested in psychiatry, I tell them to study the DSM. I explain to them that when I was in medical school my dermatology professor told us that if we could recognize the 10 most common dermatologic disorders, we would be able to recognize 90% of the skin disorders we would see. It is similar in psychiatry – thus, my five categories.

However, because I do not want them thinking that only schizophrenia causes psychosis, I let them know that at least 40 different factors cause people to be psychotic indicated by auditory hallucinations. Those 40 factors are: 1) acute alcohol intoxication, 2) alcohol withdrawal, 3) alcoholism, 4) Alzheimer’s disease, 5) benzodiazepine withdrawal, 6) cocaine abuse and addiction, 7) chemical poisoning, 8) dehydration, 9) delirium, 10) dissociative disorders, 11) electrolyte imbalances, 12) encephalopathy of various forms, 13) ecstasy, 14) extreme fatigue, 15) falling asleep, 16) fetal alcohol exposure, 17) grief, 18) hallucinogen use, 19) heroin abuse and dependence, 20) high fever, 21) hyperglycemia, 22) hypoglycemia, 23) intellectual disability, 24) lupus, 25) major depression, 26) mania, 27) methamphetamine use, 28) Parkinson’s disease, 29) phencyclidine, 30) postictal states, 31) posttraumatic stress disorder, 32) schizoid or schizotypal personality disorder, 33) schizophrenia, 34) sleep deprivation, 35) sleep paralysis, 36) solvent abuse, 37) traumatic brain injury, 38) temporal lobe epilepsy, 39) uremia. Lastly, I ask them about No. 40 – “normal” (For example, have you ever been walking down the street and thought you heard someone calling your name, but when you turned around no one was there?). Of course, there are many more causes of psychosis, but keeping it simple makes the principle easier to remember.

Regarding affective disorders, I point out to them, as I did in a previous column, that there is a huge difference between major depressive disorders, unhappiness, or sadness, grief, and demoralization. Regarding anxiety disorders, I let the medical students know that, like personality disorders, there is a lot of comorbidity. Yet, if they can distinguish brain damage, psychosis, and affective disorders from anxiety and personality disorders, that will be good enough.

In keeping with trying to help medical students not make assumptions, I always ask them what’s wrong with people who wash their hands 30 times a day. Invariably, the answer is obsessive-compulsive disorder. So, next I ask: Isn’t it possible that the person who washes his hands 30 times a day is a surgeon – or perhaps a patient with schizophrenia who thinks that Martians are beaming germs to his hands?

I guess I raise this issue because I am concerned with the future of psychiatry, and I think that my approach to medical school education provides a framework that can help students learn how to think about and provide care for psychiatric patients.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of the Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. If you have tricks of the medical school teaching trade that you would like to share, email Dr. Bell at [email protected].

I have the unfortunate task of trying to teach medical students about psychiatry. I say “unfortunate,” as most of them find psychiatry a difficult art to understand, and they seem reluctant to classify psychiatry as a branch of medicine.

Wavebreakmedia/Thinkstock

In my efforts to keep things simple, I tell that them psychiatry is one of the most difficult branches of medicine as there are very few objective measures we can rely on to make sense of people’s behavior. Regrettably, the American Psychiatric Association’s Diagnostic and Statistical Manual only seems to confuse them more. So, I remind them that, in medicine, 90%-95% of diagnoses can be obtained from doing a good history, and, if we are lucky a drug level will show drugs in the system, a CT scan without contrast will show cerebral atrophy, or there will be a lab result that will be abnormal and point to a diagnosis. But mostly what they will be seeing is unusual behavior they are unable to classify.

So I try to make psychiatric diagnosis more manageable for them by telling them there are essentially five overarching categories of psychiatric illness: identifiable brain damage, psychosis, affective disorders, anxiety disorders, and personality disorders. Under the brain damage category, I include the short- and long-term effects of drugs, major neurocognitive disorders (called dementia before DSM-5), cerebrovascular infarcts, traumatic brain injury, and neurodevelopmental disorders. For their exams and, if they are interested in psychiatry, I tell them to study the DSM. I explain to them that when I was in medical school my dermatology professor told us that if we could recognize the 10 most common dermatologic disorders, we would be able to recognize 90% of the skin disorders we would see. It is similar in psychiatry – thus, my five categories.

However, because I do not want them thinking that only schizophrenia causes psychosis, I let them know that at least 40 different factors cause people to be psychotic indicated by auditory hallucinations. Those 40 factors are: 1) acute alcohol intoxication, 2) alcohol withdrawal, 3) alcoholism, 4) Alzheimer’s disease, 5) benzodiazepine withdrawal, 6) cocaine abuse and addiction, 7) chemical poisoning, 8) dehydration, 9) delirium, 10) dissociative disorders, 11) electrolyte imbalances, 12) encephalopathy of various forms, 13) ecstasy, 14) extreme fatigue, 15) falling asleep, 16) fetal alcohol exposure, 17) grief, 18) hallucinogen use, 19) heroin abuse and dependence, 20) high fever, 21) hyperglycemia, 22) hypoglycemia, 23) intellectual disability, 24) lupus, 25) major depression, 26) mania, 27) methamphetamine use, 28) Parkinson’s disease, 29) phencyclidine, 30) postictal states, 31) posttraumatic stress disorder, 32) schizoid or schizotypal personality disorder, 33) schizophrenia, 34) sleep deprivation, 35) sleep paralysis, 36) solvent abuse, 37) traumatic brain injury, 38) temporal lobe epilepsy, 39) uremia. Lastly, I ask them about No. 40 – “normal” (For example, have you ever been walking down the street and thought you heard someone calling your name, but when you turned around no one was there?). Of course, there are many more causes of psychosis, but keeping it simple makes the principle easier to remember.

Regarding affective disorders, I point out to them, as I did in a previous column, that there is a huge difference between major depressive disorders, unhappiness, or sadness, grief, and demoralization. Regarding anxiety disorders, I let the medical students know that, like personality disorders, there is a lot of comorbidity. Yet, if they can distinguish brain damage, psychosis, and affective disorders from anxiety and personality disorders, that will be good enough.

In keeping with trying to help medical students not make assumptions, I always ask them what’s wrong with people who wash their hands 30 times a day. Invariably, the answer is obsessive-compulsive disorder. So, next I ask: Isn’t it possible that the person who washes his hands 30 times a day is a surgeon – or perhaps a patient with schizophrenia who thinks that Martians are beaming germs to his hands?

I guess I raise this issue because I am concerned with the future of psychiatry, and I think that my approach to medical school education provides a framework that can help students learn how to think about and provide care for psychiatric patients.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of the Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. If you have tricks of the medical school teaching trade that you would like to share, email Dr. Bell at [email protected].

I have the unfortunate task of trying to teach medical students about psychiatry. I say “unfortunate,” as most of them find psychiatry a difficult art to understand, and they seem reluctant to classify psychiatry as a branch of medicine.

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In my efforts to keep things simple, I tell that them psychiatry is one of the most difficult branches of medicine as there are very few objective measures we can rely on to make sense of people’s behavior. Regrettably, the American Psychiatric Association’s Diagnostic and Statistical Manual only seems to confuse them more. So, I remind them that, in medicine, 90%-95% of diagnoses can be obtained from doing a good history, and, if we are lucky a drug level will show drugs in the system, a CT scan without contrast will show cerebral atrophy, or there will be a lab result that will be abnormal and point to a diagnosis. But mostly what they will be seeing is unusual behavior they are unable to classify.

So I try to make psychiatric diagnosis more manageable for them by telling them there are essentially five overarching categories of psychiatric illness: identifiable brain damage, psychosis, affective disorders, anxiety disorders, and personality disorders. Under the brain damage category, I include the short- and long-term effects of drugs, major neurocognitive disorders (called dementia before DSM-5), cerebrovascular infarcts, traumatic brain injury, and neurodevelopmental disorders. For their exams and, if they are interested in psychiatry, I tell them to study the DSM. I explain to them that when I was in medical school my dermatology professor told us that if we could recognize the 10 most common dermatologic disorders, we would be able to recognize 90% of the skin disorders we would see. It is similar in psychiatry – thus, my five categories.

However, because I do not want them thinking that only schizophrenia causes psychosis, I let them know that at least 40 different factors cause people to be psychotic indicated by auditory hallucinations. Those 40 factors are: 1) acute alcohol intoxication, 2) alcohol withdrawal, 3) alcoholism, 4) Alzheimer’s disease, 5) benzodiazepine withdrawal, 6) cocaine abuse and addiction, 7) chemical poisoning, 8) dehydration, 9) delirium, 10) dissociative disorders, 11) electrolyte imbalances, 12) encephalopathy of various forms, 13) ecstasy, 14) extreme fatigue, 15) falling asleep, 16) fetal alcohol exposure, 17) grief, 18) hallucinogen use, 19) heroin abuse and dependence, 20) high fever, 21) hyperglycemia, 22) hypoglycemia, 23) intellectual disability, 24) lupus, 25) major depression, 26) mania, 27) methamphetamine use, 28) Parkinson’s disease, 29) phencyclidine, 30) postictal states, 31) posttraumatic stress disorder, 32) schizoid or schizotypal personality disorder, 33) schizophrenia, 34) sleep deprivation, 35) sleep paralysis, 36) solvent abuse, 37) traumatic brain injury, 38) temporal lobe epilepsy, 39) uremia. Lastly, I ask them about No. 40 – “normal” (For example, have you ever been walking down the street and thought you heard someone calling your name, but when you turned around no one was there?). Of course, there are many more causes of psychosis, but keeping it simple makes the principle easier to remember.

Regarding affective disorders, I point out to them, as I did in a previous column, that there is a huge difference between major depressive disorders, unhappiness, or sadness, grief, and demoralization. Regarding anxiety disorders, I let the medical students know that, like personality disorders, there is a lot of comorbidity. Yet, if they can distinguish brain damage, psychosis, and affective disorders from anxiety and personality disorders, that will be good enough.

In keeping with trying to help medical students not make assumptions, I always ask them what’s wrong with people who wash their hands 30 times a day. Invariably, the answer is obsessive-compulsive disorder. So, next I ask: Isn’t it possible that the person who washes his hands 30 times a day is a surgeon – or perhaps a patient with schizophrenia who thinks that Martians are beaming germs to his hands?

I guess I raise this issue because I am concerned with the future of psychiatry, and I think that my approach to medical school education provides a framework that can help students learn how to think about and provide care for psychiatric patients.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of the Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. If you have tricks of the medical school teaching trade that you would like to share, email Dr. Bell at [email protected].

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). As part of VA’s New Models of Care initiative, the 5 CoEPCEs are using VA primary care settings to develop and test innovative approaches to prepare physician residents and students, advanced practice nurses (APRNs), undergraduate nursing students, and other health professions trainees (such as pharmacy, social work, psychology, physician assistants) for primary care practice. The CoEPCE sites are developing, implementing, and evaluating curricula to prepare learners from relevant professions to practice in patientcentered, interprofessional team-based primary care settings. Patient aligned care teams (PACTs) that have 2 or more health professions trainees engaged in learning, working, and teaching are known as interprofessional academic PACTs (iAPACTs), which is the preferred model for the VA.

The Cleveland Transforming Outpatient Care (TOPC)-CoEPCE was designed for collaborative learning among nurse practitioner (NP) students and physician residents. Its robust curriculum consists of a dedicated half-day of didactics for all learners, interprofessional quality improvement projects, panel management sessions, and primary care clinical sessions for nursing and physician learners that include the dyad workplace learning model.

In 2015, the OAA lead evaluator observed the TOPC-CoEPCE dyad model process, reviewed background documents, and conducted 10 open-ended interviews with TOPC-CoEPCE staff, participating trainees, faculty, and affiliate leadership. Informants described their involvement, challenges encountered, and benefits of the TOPCCoEPC dyad model to participants, veterans, VA, and affiliates.

Lack of Interprofessional Learning Opportunities

Current health care professional education models typically do not have many workplace learning settings where physician and nursing trainees learn together and provide patient-centered care. Often in a shared clinical environment, trainees may engage in “parallel play,” which can result in physician trainees and NP students learning independently and being ill-prepared to practice effectively together.

Moreover, trainees from different professions have different learning needs. For example, less experienced NP students require greater time, supervision, and evaluation of their patient care skills. On the other hand, senior physician residents, who require less clinical instruction, need to be engaged in ways that provide opportunities to enhance their ambulatory teaching skills. Although enhancement of resident teaching skills occurs in the inpatient hospital setting, there have been limited teaching experiences for residents in a primary care setting where the instruction is traditionally faculty-based. The TOPCCoEPCE dyad model offers an opportunity to simultaneously provide trainees with a true interprofessional experience through advancement of skills in primary care, teamwork, and teaching, while addressing health care needs.

The Dyad Model

In 2011, the OAA directed COEPCE sites to develop innovative curriculum and workplace learning strategies to create more opportunities for physician and NP trainees to work as a team. There is evidence demonstrating that when students develop a shared understanding of each other’s skill set, care procedures, and values, patient care is improved.¹ Further, training in pairs can be an effective strategy in education of preclerkship medical students.² In April 2013, TOPC-CoEPCE staff asked representatives from the Student-Run Clinic at Case Western Reserve University (CWRU) in Cleveland, Ohio, to present their approach to pairing nursing and medical students in clinic under supervision by volunteer faculty. However, formal structure and curricular objectives were lacking. To address diverse TOPCCoEPCE trainee needs and create a team approach to patient care, the staff formalized and developed a workplace curriculum called the dyad model. Specifically, the model pairs 1 NP student with a senior (PGY2 or PGY3) physician resident to care for ambulatory patients as a dyad teaching/learning team. The dyad model has 3 goals: improving clinical performance, learning team dynamics, and improving the physician resident’s teaching skills in an ambulatory setting.

Planning and Implementation

Planning the dyad model took 4 months. Initial conceptualization of the model was discussed at TOPC-CoEPCE infrastructure meetings. Workgroups with representatives from medicine, nursing, evaluation and medical center administration were formed to finalize the model. The workgroups met weekly or biweekly to develop protocols for scheduling, ongoing monitoring and assessment, microteaching session curriculum development, and logistics. A pilot program was initiated for 1 month with 2 dyads to monitor learner progress and improve components, such as adjusting the patient exam start times and curriculum. In maintaining the program, the workgroups continue to meet monthly to check for areas for further improvement and maintain dissemination activities.

Curriculum

The dyad model is a novel opportunity to have trainees from different professions not only collaborate in the care of the same patient at the same time, but also negotiate their respective responsibilities preand postvisit. The experience focuses on interprofessional relationships and open communication. TOPC-CoEPCE used a modified version of the RIME (Reporter-Interpreter-Manager-Educator) model called the O-RIME model (Table 1), which includes an observer (O) phase as the first component for clarification about a beginners’ role^.3,4 

Four dyad pairs provide collaborative clinical care for veterans during one halfday session per week. The dyad conducts 4 hour-long patient visits per session. To be a dyad participant, the physician residents must be at least a PGY2, and their schedule must align with the NP student clinic schedule. Participation is mandatory for both NP students and physician residents. TOPC staff assemble the pairs.

The dyad model requires knowledge of the clinical and curricular interface and when to block the dyad team members’ schedules for 4 patients instead of 6. Physician residents are in the TOPC-CoEPCE for 12 weeks and then on inpatient for 12 weeks. Depending on the nursing school affiliate, NP student trainees are scheduled for either a 6- or 12-month TOPC-CoEPCE experience. For the 12-month NP students, they are paired with up to 4 internal medicine residents over the course of their dyad participation so they can experience different teaching styles of each resident while developing more varied interprofessional communication skills.

Faculty Roles and Development

The dyad model also seeks to address the paucity of deliberate interprofessional precepting in academic primary care settings. The TOPC-CoEPCE staff decided to use the existing primary care clinic faculty development series bimonthly for 1 hour each. The dyad model team members presented sessions covering foundational material in interprofessional teaching and precepting skills, which prepare faculty to precept for different professions and the dyad teams. It is important for preceptors to develop awareness of learners from different professions and the corresponding educational trajectories, so they can communicate with paired trainees of differing professions and academic levels who may require different levels of discussion.

Resources

By utilizing advanced residents as teachers, faculty were able to increase the number of learners in the clinic without increasing the number preceptors. For example, precepting a student typically requires more preceptor time, especially when we consider that the preceptor must also see the patient. The TOPC-CoEPCE faculty run the microteaching sessions, and an evaluator monitors and evaluates the program. The microteaching sessions were derived from several teaching resources.

Monitoring and Assessment

The Cleveland TOPC administered 2 different surveys developed by the Dyad Model Infrastructure and Evaluation workgroup. A 7-item survey assesses dyad team communication and interprofessional team functioning, and an 8-item survey assesses the teaching/mentoring of the resident as teacher. Both were collected from all participants to evaluate the residents’ and students’ point of view. Surveys are collected in the first and last weeks of the dyad experience. Feedback from participants has been used to make improvements to the program (eg, monitoring how the dyad teams are functioning, coaching individual learners).

Partnerships

In addition to TOPC staff and faculty support and engagement, the initiative has benefited from partnerships with VA clinic staff and with the associated academic affiliates. In particular, the Associate Chief of General Internal Medicine at the Cleveland VA medical center and interim clinic director helped institute changes to the primary care clinic structure. Additionally, buy-in from the clinic nurse manager was needed to make adjustments with staff schedules and clinic resources. To implement the dyad model, the clinic director had to approve reductions in the residents’ clinic loads for the mornings when they participated.

The NP affiliates’ faculty at the schools of nursing are integral partners who assist with student recruitment and participate in the planning and refinement of TOPCCoEPCE components. The Frances Payne Bolton School of Nursing at CWRU and the Breen School of Nursing of Ursuline College in Pepper Pike, Ohio, were involved in the planning stages and continue to receive monthly updates from TOPC-CoEPCE. Similarly, the CWRU School of Medicine and Cleveland Clinic Foundation affiliates contribute on an ongoing basis to the improvement and implementation process.

Discussion

One challenge has been advancing aspects of a nonhierarchical team approach while it is a teacher-student relationship. The dyad model is viewed as an opportunity to recognize nonhierarchical structures and teach negotiation and communication skills as well as increase interprofessional understanding of each other’s education, expertise, and scope of practice.

Another challenge is accommodating the diversity in NP training and clinical expertise. The NP student participants are in either the first or second year of their academic program. This is a challenge since both physician residents and physician faculty preceptors need to assess the NP students’ skills before providing opportunities to build on their skill level. Staff members have learned the value of checking in weekly on this issue.

Factors for Success

VA facility support and TOPC-CoEPCE leadership with the operations/academic partnership remain critical to integrating and sustaining the model into the Cleveland primary care clinic. The expertise of TOPC-CoEPCE dyad model faculty who serve as facilitators has been crucial, as they oversee team development concepts such as developing problem solving and negotiation skills. The workgroups ensured that faculty were skilled in understanding the different types of learners and provided guidance to dyad teams. Another success factor was the continual monitoring of the process and real-time evaluation of the program to adapt the model as needed.

Accomplishments and Benefits

There is evidence that the dyad model is achieving its goals: Trainees are using team skills during and outside formal dyad pairs; NP students report improvements in skill levels and comfort; and physician residents feel the teaching role in the dyad pair is an opportunity for them to improve their practice.

Interprofessional Educational Capacity

The dyad model complements the curriculum components and advances trainee understanding of 4 core domains: shared decision-making (SDM), sustained relationships (SR), interprofessional collaboration (IPC), and performance improvement (PI) (Table 2). The dyad model supports the other CoEPCE interprofessional education activities and is reinforced by these activities. The model is a learning laboratory for studying team dynamics and developing a curriculum that strengthens a team approach to patient-centered care.

Participants’ Knowledge, Attitudes, Skills, and Competencies

As of May 2015, 35 trainees (21 internal medicine physician residents and 14 NP students) have participated in dyads. Because physician residents participate over 2 years and may partner with more than 1 NP student, this has resulted in 27 dyad pairs in this time frame. Findings from an analysis of evaluations suggest that the dyad pair trainees learn from one another, and the model provides a safe space where trainees can practice and increase their confidence.^1,6,7 The NP students seem to increase clinical skills quickly—expanding physical exam skills, building a differential diagnosis, and formulating therapeutic plans—and progressing to the Interpreter and Manager levels in the O-RIME model. The physician resident achieves the Educator level.

As of September 2015, the results from the pairs who completed beginning and end evaluations show that the physician residents increased the amount of feedback they provided about performance to the student, and likewise the student NPs also felt they received an increased amount of feedback about performance from the physician resident. In addition, physician residents reported improving the most in the following areas: allowing the student to make commitments in diagnoses and treatment plans and asking the student to provide supporting evidence for their commitment to the diagnoses. NP students reported the largest increases in receiving weekly feedback about their performance from the physician and their ability to listen to the patient.^1,6,7

Interprofessional Collaboration

The TOPC-CoEPCE staff observed strengthened dyad pair relationships and mutual respect between the dyad partners. Trainees communicate with each other and work together to provide care of the patient. Second, dyad pair partners are learning about the other profession—their trajectory, their education model, and their differences. The physician resident develops an awareness of the partner NP student’s knowledge and expertise, such as their experience of social and psychological factors to become a more effective teacher, contributing to patient-centered care. The evaluation results illustrate increased ability of trainees to give and receive feedback and the change in roles for providing diagnosis and providing supporting evidence within the TOPCCoEPCE dyad team.^6-8

The Future

The model has broad applicability for interprofessional education in the VA since it enhances skills that providers need to work in a PACT/PCMH model. Additionally, the TOPC-CoEPCE dyad model has proven to be an effective interprofessional training experience for its affiliates and may have applicability in other VA/affiliate training programs. The dyad model can be adapted to different trainee types in the ambulatory care setting. The TOPCCoEPCE is piloting a version of the dyad with NP residents (postgraduate) and first-year medical students. Additionally, the TOPCCoEPCE is paving the way for integrating improvement of physician resident teaching skills into the primary care setting and facilitating bidirectional teaching among different professions. TOPC-CoEPCE intends to develop additional resources to facilitate use of the model application in other settings such as the dyad implementation template.

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). As part of VA’s New Models of Care initiative, the 5 CoEPCEs are using VA primary care settings to develop and test innovative approaches to prepare physician residents and students, advanced practice nurses (APRNs), undergraduate nursing students, and other health professions trainees (such as pharmacy, social work, psychology, physician assistants) for primary care practice. The CoEPCE sites are developing, implementing, and evaluating curricula to prepare learners from relevant professions to practice in patientcentered, interprofessional team-based primary care settings. Patient aligned care teams (PACTs) that have 2 or more health professions trainees engaged in learning, working, and teaching are known as interprofessional academic PACTs (iAPACTs), which is the preferred model for the VA.

The Cleveland Transforming Outpatient Care (TOPC)-CoEPCE was designed for collaborative learning among nurse practitioner (NP) students and physician residents. Its robust curriculum consists of a dedicated half-day of didactics for all learners, interprofessional quality improvement projects, panel management sessions, and primary care clinical sessions for nursing and physician learners that include the dyad workplace learning model.

In 2015, the OAA lead evaluator observed the TOPC-CoEPCE dyad model process, reviewed background documents, and conducted 10 open-ended interviews with TOPC-CoEPCE staff, participating trainees, faculty, and affiliate leadership. Informants described their involvement, challenges encountered, and benefits of the TOPCCoEPC dyad model to participants, veterans, VA, and affiliates.

Lack of Interprofessional Learning Opportunities

Current health care professional education models typically do not have many workplace learning settings where physician and nursing trainees learn together and provide patient-centered care. Often in a shared clinical environment, trainees may engage in “parallel play,” which can result in physician trainees and NP students learning independently and being ill-prepared to practice effectively together.

Moreover, trainees from different professions have different learning needs. For example, less experienced NP students require greater time, supervision, and evaluation of their patient care skills. On the other hand, senior physician residents, who require less clinical instruction, need to be engaged in ways that provide opportunities to enhance their ambulatory teaching skills. Although enhancement of resident teaching skills occurs in the inpatient hospital setting, there have been limited teaching experiences for residents in a primary care setting where the instruction is traditionally faculty-based. The TOPCCoEPCE dyad model offers an opportunity to simultaneously provide trainees with a true interprofessional experience through advancement of skills in primary care, teamwork, and teaching, while addressing health care needs.

The Dyad Model

In 2011, the OAA directed COEPCE sites to develop innovative curriculum and workplace learning strategies to create more opportunities for physician and NP trainees to work as a team. There is evidence demonstrating that when students develop a shared understanding of each other’s skill set, care procedures, and values, patient care is improved.¹ Further, training in pairs can be an effective strategy in education of preclerkship medical students.² In April 2013, TOPC-CoEPCE staff asked representatives from the Student-Run Clinic at Case Western Reserve University (CWRU) in Cleveland, Ohio, to present their approach to pairing nursing and medical students in clinic under supervision by volunteer faculty. However, formal structure and curricular objectives were lacking. To address diverse TOPCCoEPCE trainee needs and create a team approach to patient care, the staff formalized and developed a workplace curriculum called the dyad model. Specifically, the model pairs 1 NP student with a senior (PGY2 or PGY3) physician resident to care for ambulatory patients as a dyad teaching/learning team. The dyad model has 3 goals: improving clinical performance, learning team dynamics, and improving the physician resident’s teaching skills in an ambulatory setting.

Planning and Implementation

Planning the dyad model took 4 months. Initial conceptualization of the model was discussed at TOPC-CoEPCE infrastructure meetings. Workgroups with representatives from medicine, nursing, evaluation and medical center administration were formed to finalize the model. The workgroups met weekly or biweekly to develop protocols for scheduling, ongoing monitoring and assessment, microteaching session curriculum development, and logistics. A pilot program was initiated for 1 month with 2 dyads to monitor learner progress and improve components, such as adjusting the patient exam start times and curriculum. In maintaining the program, the workgroups continue to meet monthly to check for areas for further improvement and maintain dissemination activities.

Curriculum

The dyad model is a novel opportunity to have trainees from different professions not only collaborate in the care of the same patient at the same time, but also negotiate their respective responsibilities preand postvisit. The experience focuses on interprofessional relationships and open communication. TOPC-CoEPCE used a modified version of the RIME (Reporter-Interpreter-Manager-Educator) model called the O-RIME model (Table 1), which includes an observer (O) phase as the first component for clarification about a beginners’ role^.3,4 

Four dyad pairs provide collaborative clinical care for veterans during one halfday session per week. The dyad conducts 4 hour-long patient visits per session. To be a dyad participant, the physician residents must be at least a PGY2, and their schedule must align with the NP student clinic schedule. Participation is mandatory for both NP students and physician residents. TOPC staff assemble the pairs.

The dyad model requires knowledge of the clinical and curricular interface and when to block the dyad team members’ schedules for 4 patients instead of 6. Physician residents are in the TOPC-CoEPCE for 12 weeks and then on inpatient for 12 weeks. Depending on the nursing school affiliate, NP student trainees are scheduled for either a 6- or 12-month TOPC-CoEPCE experience. For the 12-month NP students, they are paired with up to 4 internal medicine residents over the course of their dyad participation so they can experience different teaching styles of each resident while developing more varied interprofessional communication skills.

Faculty Roles and Development

The dyad model also seeks to address the paucity of deliberate interprofessional precepting in academic primary care settings. The TOPC-CoEPCE staff decided to use the existing primary care clinic faculty development series bimonthly for 1 hour each. The dyad model team members presented sessions covering foundational material in interprofessional teaching and precepting skills, which prepare faculty to precept for different professions and the dyad teams. It is important for preceptors to develop awareness of learners from different professions and the corresponding educational trajectories, so they can communicate with paired trainees of differing professions and academic levels who may require different levels of discussion.

Resources

By utilizing advanced residents as teachers, faculty were able to increase the number of learners in the clinic without increasing the number preceptors. For example, precepting a student typically requires more preceptor time, especially when we consider that the preceptor must also see the patient. The TOPC-CoEPCE faculty run the microteaching sessions, and an evaluator monitors and evaluates the program. The microteaching sessions were derived from several teaching resources.

Monitoring and Assessment

The Cleveland TOPC administered 2 different surveys developed by the Dyad Model Infrastructure and Evaluation workgroup. A 7-item survey assesses dyad team communication and interprofessional team functioning, and an 8-item survey assesses the teaching/mentoring of the resident as teacher. Both were collected from all participants to evaluate the residents’ and students’ point of view. Surveys are collected in the first and last weeks of the dyad experience. Feedback from participants has been used to make improvements to the program (eg, monitoring how the dyad teams are functioning, coaching individual learners).

Partnerships

In addition to TOPC staff and faculty support and engagement, the initiative has benefited from partnerships with VA clinic staff and with the associated academic affiliates. In particular, the Associate Chief of General Internal Medicine at the Cleveland VA medical center and interim clinic director helped institute changes to the primary care clinic structure. Additionally, buy-in from the clinic nurse manager was needed to make adjustments with staff schedules and clinic resources. To implement the dyad model, the clinic director had to approve reductions in the residents’ clinic loads for the mornings when they participated.

The NP affiliates’ faculty at the schools of nursing are integral partners who assist with student recruitment and participate in the planning and refinement of TOPCCoEPCE components. The Frances Payne Bolton School of Nursing at CWRU and the Breen School of Nursing of Ursuline College in Pepper Pike, Ohio, were involved in the planning stages and continue to receive monthly updates from TOPC-CoEPCE. Similarly, the CWRU School of Medicine and Cleveland Clinic Foundation affiliates contribute on an ongoing basis to the improvement and implementation process.

Discussion

One challenge has been advancing aspects of a nonhierarchical team approach while it is a teacher-student relationship. The dyad model is viewed as an opportunity to recognize nonhierarchical structures and teach negotiation and communication skills as well as increase interprofessional understanding of each other’s education, expertise, and scope of practice.

Another challenge is accommodating the diversity in NP training and clinical expertise. The NP student participants are in either the first or second year of their academic program. This is a challenge since both physician residents and physician faculty preceptors need to assess the NP students’ skills before providing opportunities to build on their skill level. Staff members have learned the value of checking in weekly on this issue.

Factors for Success

VA facility support and TOPC-CoEPCE leadership with the operations/academic partnership remain critical to integrating and sustaining the model into the Cleveland primary care clinic. The expertise of TOPC-CoEPCE dyad model faculty who serve as facilitators has been crucial, as they oversee team development concepts such as developing problem solving and negotiation skills. The workgroups ensured that faculty were skilled in understanding the different types of learners and provided guidance to dyad teams. Another success factor was the continual monitoring of the process and real-time evaluation of the program to adapt the model as needed.

Accomplishments and Benefits

There is evidence that the dyad model is achieving its goals: Trainees are using team skills during and outside formal dyad pairs; NP students report improvements in skill levels and comfort; and physician residents feel the teaching role in the dyad pair is an opportunity for them to improve their practice.

Interprofessional Educational Capacity

The dyad model complements the curriculum components and advances trainee understanding of 4 core domains: shared decision-making (SDM), sustained relationships (SR), interprofessional collaboration (IPC), and performance improvement (PI) (Table 2). The dyad model supports the other CoEPCE interprofessional education activities and is reinforced by these activities. The model is a learning laboratory for studying team dynamics and developing a curriculum that strengthens a team approach to patient-centered care.

Participants’ Knowledge, Attitudes, Skills, and Competencies

As of May 2015, 35 trainees (21 internal medicine physician residents and 14 NP students) have participated in dyads. Because physician residents participate over 2 years and may partner with more than 1 NP student, this has resulted in 27 dyad pairs in this time frame. Findings from an analysis of evaluations suggest that the dyad pair trainees learn from one another, and the model provides a safe space where trainees can practice and increase their confidence.^1,6,7 The NP students seem to increase clinical skills quickly—expanding physical exam skills, building a differential diagnosis, and formulating therapeutic plans—and progressing to the Interpreter and Manager levels in the O-RIME model. The physician resident achieves the Educator level.

As of September 2015, the results from the pairs who completed beginning and end evaluations show that the physician residents increased the amount of feedback they provided about performance to the student, and likewise the student NPs also felt they received an increased amount of feedback about performance from the physician resident. In addition, physician residents reported improving the most in the following areas: allowing the student to make commitments in diagnoses and treatment plans and asking the student to provide supporting evidence for their commitment to the diagnoses. NP students reported the largest increases in receiving weekly feedback about their performance from the physician and their ability to listen to the patient.^1,6,7

Interprofessional Collaboration

The TOPC-CoEPCE staff observed strengthened dyad pair relationships and mutual respect between the dyad partners. Trainees communicate with each other and work together to provide care of the patient. Second, dyad pair partners are learning about the other profession—their trajectory, their education model, and their differences. The physician resident develops an awareness of the partner NP student’s knowledge and expertise, such as their experience of social and psychological factors to become a more effective teacher, contributing to patient-centered care. The evaluation results illustrate increased ability of trainees to give and receive feedback and the change in roles for providing diagnosis and providing supporting evidence within the TOPCCoEPCE dyad team.^6-8

The Future

The model has broad applicability for interprofessional education in the VA since it enhances skills that providers need to work in a PACT/PCMH model. Additionally, the TOPC-CoEPCE dyad model has proven to be an effective interprofessional training experience for its affiliates and may have applicability in other VA/affiliate training programs. The dyad model can be adapted to different trainee types in the ambulatory care setting. The TOPCCoEPCE is piloting a version of the dyad with NP residents (postgraduate) and first-year medical students. Additionally, the TOPCCoEPCE is paving the way for integrating improvement of physician resident teaching skills into the primary care setting and facilitating bidirectional teaching among different professions. TOPC-CoEPCE intends to develop additional resources to facilitate use of the model application in other settings such as the dyad implementation template.

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). As part of VA’s New Models of Care initiative, the 5 CoEPCEs are using VA primary care settings to develop and test innovative approaches to prepare physician residents and students, advanced practice nurses (APRNs), undergraduate nursing students, and other health professions trainees (such as pharmacy, social work, psychology, physician assistants) for primary care practice. The CoEPCE sites are developing, implementing, and evaluating curricula to prepare learners from relevant professions to practice in patientcentered, interprofessional team-based primary care settings. Patient aligned care teams (PACTs) that have 2 or more health professions trainees engaged in learning, working, and teaching are known as interprofessional academic PACTs (iAPACTs), which is the preferred model for the VA.

The Cleveland Transforming Outpatient Care (TOPC)-CoEPCE was designed for collaborative learning among nurse practitioner (NP) students and physician residents. Its robust curriculum consists of a dedicated half-day of didactics for all learners, interprofessional quality improvement projects, panel management sessions, and primary care clinical sessions for nursing and physician learners that include the dyad workplace learning model.

In 2015, the OAA lead evaluator observed the TOPC-CoEPCE dyad model process, reviewed background documents, and conducted 10 open-ended interviews with TOPC-CoEPCE staff, participating trainees, faculty, and affiliate leadership. Informants described their involvement, challenges encountered, and benefits of the TOPCCoEPC dyad model to participants, veterans, VA, and affiliates.

Lack of Interprofessional Learning Opportunities

Current health care professional education models typically do not have many workplace learning settings where physician and nursing trainees learn together and provide patient-centered care. Often in a shared clinical environment, trainees may engage in “parallel play,” which can result in physician trainees and NP students learning independently and being ill-prepared to practice effectively together.

Moreover, trainees from different professions have different learning needs. For example, less experienced NP students require greater time, supervision, and evaluation of their patient care skills. On the other hand, senior physician residents, who require less clinical instruction, need to be engaged in ways that provide opportunities to enhance their ambulatory teaching skills. Although enhancement of resident teaching skills occurs in the inpatient hospital setting, there have been limited teaching experiences for residents in a primary care setting where the instruction is traditionally faculty-based. The TOPCCoEPCE dyad model offers an opportunity to simultaneously provide trainees with a true interprofessional experience through advancement of skills in primary care, teamwork, and teaching, while addressing health care needs.

The Dyad Model

In 2011, the OAA directed COEPCE sites to develop innovative curriculum and workplace learning strategies to create more opportunities for physician and NP trainees to work as a team. There is evidence demonstrating that when students develop a shared understanding of each other’s skill set, care procedures, and values, patient care is improved.¹ Further, training in pairs can be an effective strategy in education of preclerkship medical students.² In April 2013, TOPC-CoEPCE staff asked representatives from the Student-Run Clinic at Case Western Reserve University (CWRU) in Cleveland, Ohio, to present their approach to pairing nursing and medical students in clinic under supervision by volunteer faculty. However, formal structure and curricular objectives were lacking. To address diverse TOPCCoEPCE trainee needs and create a team approach to patient care, the staff formalized and developed a workplace curriculum called the dyad model. Specifically, the model pairs 1 NP student with a senior (PGY2 or PGY3) physician resident to care for ambulatory patients as a dyad teaching/learning team. The dyad model has 3 goals: improving clinical performance, learning team dynamics, and improving the physician resident’s teaching skills in an ambulatory setting.

Planning and Implementation

Planning the dyad model took 4 months. Initial conceptualization of the model was discussed at TOPC-CoEPCE infrastructure meetings. Workgroups with representatives from medicine, nursing, evaluation and medical center administration were formed to finalize the model. The workgroups met weekly or biweekly to develop protocols for scheduling, ongoing monitoring and assessment, microteaching session curriculum development, and logistics. A pilot program was initiated for 1 month with 2 dyads to monitor learner progress and improve components, such as adjusting the patient exam start times and curriculum. In maintaining the program, the workgroups continue to meet monthly to check for areas for further improvement and maintain dissemination activities.

Curriculum

The dyad model is a novel opportunity to have trainees from different professions not only collaborate in the care of the same patient at the same time, but also negotiate their respective responsibilities preand postvisit. The experience focuses on interprofessional relationships and open communication. TOPC-CoEPCE used a modified version of the RIME (Reporter-Interpreter-Manager-Educator) model called the O-RIME model (Table 1), which includes an observer (O) phase as the first component for clarification about a beginners’ role^.3,4 

Four dyad pairs provide collaborative clinical care for veterans during one halfday session per week. The dyad conducts 4 hour-long patient visits per session. To be a dyad participant, the physician residents must be at least a PGY2, and their schedule must align with the NP student clinic schedule. Participation is mandatory for both NP students and physician residents. TOPC staff assemble the pairs.

The dyad model requires knowledge of the clinical and curricular interface and when to block the dyad team members’ schedules for 4 patients instead of 6. Physician residents are in the TOPC-CoEPCE for 12 weeks and then on inpatient for 12 weeks. Depending on the nursing school affiliate, NP student trainees are scheduled for either a 6- or 12-month TOPC-CoEPCE experience. For the 12-month NP students, they are paired with up to 4 internal medicine residents over the course of their dyad participation so they can experience different teaching styles of each resident while developing more varied interprofessional communication skills.

Faculty Roles and Development

The dyad model also seeks to address the paucity of deliberate interprofessional precepting in academic primary care settings. The TOPC-CoEPCE staff decided to use the existing primary care clinic faculty development series bimonthly for 1 hour each. The dyad model team members presented sessions covering foundational material in interprofessional teaching and precepting skills, which prepare faculty to precept for different professions and the dyad teams. It is important for preceptors to develop awareness of learners from different professions and the corresponding educational trajectories, so they can communicate with paired trainees of differing professions and academic levels who may require different levels of discussion.

Resources

By utilizing advanced residents as teachers, faculty were able to increase the number of learners in the clinic without increasing the number preceptors. For example, precepting a student typically requires more preceptor time, especially when we consider that the preceptor must also see the patient. The TOPC-CoEPCE faculty run the microteaching sessions, and an evaluator monitors and evaluates the program. The microteaching sessions were derived from several teaching resources.

Monitoring and Assessment

The Cleveland TOPC administered 2 different surveys developed by the Dyad Model Infrastructure and Evaluation workgroup. A 7-item survey assesses dyad team communication and interprofessional team functioning, and an 8-item survey assesses the teaching/mentoring of the resident as teacher. Both were collected from all participants to evaluate the residents’ and students’ point of view. Surveys are collected in the first and last weeks of the dyad experience. Feedback from participants has been used to make improvements to the program (eg, monitoring how the dyad teams are functioning, coaching individual learners).

Partnerships

In addition to TOPC staff and faculty support and engagement, the initiative has benefited from partnerships with VA clinic staff and with the associated academic affiliates. In particular, the Associate Chief of General Internal Medicine at the Cleveland VA medical center and interim clinic director helped institute changes to the primary care clinic structure. Additionally, buy-in from the clinic nurse manager was needed to make adjustments with staff schedules and clinic resources. To implement the dyad model, the clinic director had to approve reductions in the residents’ clinic loads for the mornings when they participated.

The NP affiliates’ faculty at the schools of nursing are integral partners who assist with student recruitment and participate in the planning and refinement of TOPCCoEPCE components. The Frances Payne Bolton School of Nursing at CWRU and the Breen School of Nursing of Ursuline College in Pepper Pike, Ohio, were involved in the planning stages and continue to receive monthly updates from TOPC-CoEPCE. Similarly, the CWRU School of Medicine and Cleveland Clinic Foundation affiliates contribute on an ongoing basis to the improvement and implementation process.

Discussion

One challenge has been advancing aspects of a nonhierarchical team approach while it is a teacher-student relationship. The dyad model is viewed as an opportunity to recognize nonhierarchical structures and teach negotiation and communication skills as well as increase interprofessional understanding of each other’s education, expertise, and scope of practice.

Another challenge is accommodating the diversity in NP training and clinical expertise. The NP student participants are in either the first or second year of their academic program. This is a challenge since both physician residents and physician faculty preceptors need to assess the NP students’ skills before providing opportunities to build on their skill level. Staff members have learned the value of checking in weekly on this issue.

Factors for Success

VA facility support and TOPC-CoEPCE leadership with the operations/academic partnership remain critical to integrating and sustaining the model into the Cleveland primary care clinic. The expertise of TOPC-CoEPCE dyad model faculty who serve as facilitators has been crucial, as they oversee team development concepts such as developing problem solving and negotiation skills. The workgroups ensured that faculty were skilled in understanding the different types of learners and provided guidance to dyad teams. Another success factor was the continual monitoring of the process and real-time evaluation of the program to adapt the model as needed.

Accomplishments and Benefits

There is evidence that the dyad model is achieving its goals: Trainees are using team skills during and outside formal dyad pairs; NP students report improvements in skill levels and comfort; and physician residents feel the teaching role in the dyad pair is an opportunity for them to improve their practice.

Interprofessional Educational Capacity

The dyad model complements the curriculum components and advances trainee understanding of 4 core domains: shared decision-making (SDM), sustained relationships (SR), interprofessional collaboration (IPC), and performance improvement (PI) (Table 2). The dyad model supports the other CoEPCE interprofessional education activities and is reinforced by these activities. The model is a learning laboratory for studying team dynamics and developing a curriculum that strengthens a team approach to patient-centered care.

Participants’ Knowledge, Attitudes, Skills, and Competencies

As of May 2015, 35 trainees (21 internal medicine physician residents and 14 NP students) have participated in dyads. Because physician residents participate over 2 years and may partner with more than 1 NP student, this has resulted in 27 dyad pairs in this time frame. Findings from an analysis of evaluations suggest that the dyad pair trainees learn from one another, and the model provides a safe space where trainees can practice and increase their confidence.^1,6,7 The NP students seem to increase clinical skills quickly—expanding physical exam skills, building a differential diagnosis, and formulating therapeutic plans—and progressing to the Interpreter and Manager levels in the O-RIME model. The physician resident achieves the Educator level.

As of September 2015, the results from the pairs who completed beginning and end evaluations show that the physician residents increased the amount of feedback they provided about performance to the student, and likewise the student NPs also felt they received an increased amount of feedback about performance from the physician resident. In addition, physician residents reported improving the most in the following areas: allowing the student to make commitments in diagnoses and treatment plans and asking the student to provide supporting evidence for their commitment to the diagnoses. NP students reported the largest increases in receiving weekly feedback about their performance from the physician and their ability to listen to the patient.^1,6,7

Interprofessional Collaboration

The TOPC-CoEPCE staff observed strengthened dyad pair relationships and mutual respect between the dyad partners. Trainees communicate with each other and work together to provide care of the patient. Second, dyad pair partners are learning about the other profession—their trajectory, their education model, and their differences. The physician resident develops an awareness of the partner NP student’s knowledge and expertise, such as their experience of social and psychological factors to become a more effective teacher, contributing to patient-centered care. The evaluation results illustrate increased ability of trainees to give and receive feedback and the change in roles for providing diagnosis and providing supporting evidence within the TOPCCoEPCE dyad team.^6-8

The Future

The model has broad applicability for interprofessional education in the VA since it enhances skills that providers need to work in a PACT/PCMH model. Additionally, the TOPC-CoEPCE dyad model has proven to be an effective interprofessional training experience for its affiliates and may have applicability in other VA/affiliate training programs. The dyad model can be adapted to different trainee types in the ambulatory care setting. The TOPCCoEPCE is piloting a version of the dyad with NP residents (postgraduate) and first-year medical students. Additionally, the TOPCCoEPCE is paving the way for integrating improvement of physician resident teaching skills into the primary care setting and facilitating bidirectional teaching among different professions. TOPC-CoEPCE intends to develop additional resources to facilitate use of the model application in other settings such as the dyad implementation template.

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers a spectrum of phenotypes ranging from nonalcoholic fatty liver or simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) defined by histologic findings of steatosis, lobular inflammation, cytologic ballooning, and some degree of fibrosis.¹ While frequently observed in patients with at least 1 risk factor (eg, obesity, diabetes mellitus [DM], dyslipidemia, hypertension), NAFLD also is an independent risk factor for type 2 DM (T2DM), chronic kidney disease, and cardiovascular disease.² At early disease stages with absence of liver fibrosis, mortality is linked to cardiovascular and not liver disease. However, in the presence of NASH, fibrosis progression to liver cirrhosis, or hepatocellular carcinoma (HCC) represent the most important liver-related outcomes that determine morbidity and mortality.³ Mirroring the obesity and T2DM epidemics, the health care burden is projected to dramatically rise.

In the following article, we will discuss how the Veterans Health Administration (VHA) is well positioned to implement an organizational strategy of comprehensive care for veterans with NAFLD. This comprehensive care strategy should include the development of a NAFLD clinic offering care for comorbid conditions frequently present in these patients, point-of-care testing, access to clinical trials, and outcomes monitoring as a key performance target for providers and the respective facility.

NAFLD disease burden

To fully appreciate the burden of a chronic disease like NAFLD, it is important to assess its long- and short-term consequences in a comprehensive manner with regard to its clinical impact, impact on the patient, and economic impact (Figure 1).

Clinical Impact

Clinical impact is assessed based on the prevalence and natural history of NAFLD and the liver fibrosis stage and determines patient survival. Coinciding with the epidemic of obesity and T2DM, the prevalence of NAFLD in the general population in North America is 24% and even higher with older age and higher body mass index (BMI).^4,5 The prevalence for NAFLD is particularly high in patients with T2DM (47%). Of patients with T2DM and NAFLD, 65% have biopsy-proven NASH of which 15% have bridging fibrosis or liver cirrhosis.⁶

NAFLD is the fastest growing cause of cirrhosis in the US with a forecasted NAFLD population of 101 million by 2030.⁷ At the same time, the number of patients with NASH will rise to 27 million of which > 7 million will have bridging fibrosis or liver cirrhosis; hepatic decompensation events are estimated to occur in 105,430 patients with liver cirrhosis, posing a major public health threat related to organ availability for liver transplantation.⁸ Since 2013, NAFLD has been the second leading cause for liver transplantation and the top reason for transplantation in patients aged < 50 years.^9,10 As many patients with NAFLD are diagnosed with HCC at stages where liver transplantation is not an option, mortality from HCC in NAFLD patients is higher than with other etiologies as treatment options are restricted.^11,12

Compared with that of the general population, veterans seeking care are older and sicker with 43% of veterans taking > 5 prescribed medications.¹³ Of those receiving VHA care, 6.6 million veterans are either overweight or obese; 165,000 are morbidly obese with a BMI > 40.¹⁴ In addition, veterans are 2.5 times more likely to have T2DM compared with that of nonveterans. Because T2DM and obesity are the most common risk factors for NAFLD, it is not surprising that NAFLD prevalence among veterans rose 3-fold from 2003 to 2011.¹⁵ It is now estimated that 540,000 veterans will progress to NASH and 108,000 will develop bridging fibrosis or liver cirrhosis by 2030.⁸ Similar to that of the general population, liver cirrhosis is attributed to NAFLD in 15% of veterans.^15,16 NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 years and 70 years, respectively.^16,17 Shockingly, 20% of HCCs were not linked to liver cirrhosis and escaped recommended HCC screening for patients with cirrhosis.^18,19

Patient Impact

Assessment of disease burden should not be restricted to clinical outcomes as patients can experience a range of symptoms that may have significant impact on their health-related quality of life (QOL) and functional status.²⁰ Using general but not disease-specific instruments, NAFLD patients reported outcomes score low regarding fatigue, activity, and emotions.²¹ More disease-specific questionnaires may provide better and disease-specific insights as how NASH impacts patients’ QOL.^22-24

Economic Impact

There is mounting evidence that the clinical implications of NAFLD directly influence the economic burden of NAFLD.²⁵ The annual burden associated with all incident and prevalent NAFLD cases in the US has been estimated at $103 billion, and projections suggest that the expected 10-year burden of NAFLD may increase to $1.005 trillion.²⁶ It is anticipated that increased NAFLD costs will affect the VHA with billions of dollars in annual expenditures in addition to the $1.5 billion already spent annually for T2DM care (4% of the VA pharmacy budget is spent on T2DM treatment).^27-29

Current Patient Care

Obesity, DM, and dyslipidemia are common conditions managed by primary care providers (PCPs). Given the close association of these conditions with NAFLD, the PCP is often the first point of medical contact for patients with or at risk for NAFLD.³⁰ For that reason, PCP awareness of NAFLD is critical for effective management of these patients. PCPs should be actively involved in the management of patients with NAFLD with pathways in place for identifying patients at high risk of liver disease for timely referral to a specialist and adequate education on the follow-up and treatment of low-risk patients. Instead, diagnosis of NAFLD is primarily triggered by either abnormal aminotransferases or detection of steatosis on imaging performed for other indications.

Barriers to optimal management of NAFLD by PCPs have been identified and occur at different levels of patient care. In the absence of clinical practice guidelines by the American Association of Family Practice covering NAFLD and a substantial latency period without signs of symptoms, NAFLD may not be perceived as a potentially serious condition by PCPs and their patients; interestingly this holds true even for some medical specialties.^31-39 More than half of PCPs do not test their patients at highest risk for NAFLD (eg, patients with obesity or T2DM) and may be unaware of practice guidelines.^40-42

Guidelines from Europe and the US are not completely in accordance. The US guidelines are vague regarding screening and are supported by only 1 medical society, due to the lack of NASH-specific drug therapies. The European guidelines are built on the support of 3 different stakeholders covering liver diseases, obesity, and DM and the experience using noninvasive liver fibrosis assessments for patients with NAFLD. To overcome this apparent conflict, a more practical and risk-stratified approach is warranted.^41,42

Making the diagnosis can be challenging in cases with competing etiologies, such as T2DM and alcohol misuse. There also is an overreliance on aminotransferase levels to diagnose NAFLD. Significant liver disease can exist in the presence of normal aminotransferases, and this may be attributed to either spontaneous aminotransferase fluctuations or upper limits of normal that have been chosen too high.^43-47 Often additional workup by PCPs depends on the magnitude of aminotransferase abnormalities.

Even if NAFLD has been diagnosed by PCPs, identifying those with NASH is hindered by the absence of an accurate noninvasive diagnostic method and the need to perform a liver biopsy. Liver biopsy is often not considered or delayed to monitor patients with serial aminotransferases, regardless of the patient’s metabolic comorbidity profile or baseline aminotransferases.³² As a result, referral to a specialist often depends on the magnitude of the aminotransferase abnormality,^30,48 and often occurs when advanced liver disease is already present.⁴⁹ Finally, providers may not be aware of beneficial effects of lifestyle interventions and certain medications, including statins on NASH and liver fibrosis.^50-53 As NAFLD is associated with excess cardiovascular- and cancer-related morbidity and mortality, it is possible that regression of NAFLD may improve associated risk for these outcomes as well.

Framework for Comprehensive NAFLD Care

Chronic liver diseases and associated comorbidities have long been addressed by PCPs and specialty providers working in isolation and within the narrow focus of each discipline. Contrary to working in silos of the past, a coordinated management strategy with other disciplines that cover these comorbidities needs to be established, or alternatively the PCP must be aware of the management of comorbidities to execute them independently. Integration of hepatology-driven NAFLD care with other specialties involves communication, collaboration, and sharing of resources and expertise that will address patient care needs. Obviously, this cannot be undertaken in a single outpatient visit and requires vertical and longitudinal follow-up over time. One important aspect of comprehensive NAFLD care is the targeting of a particular patient population rather than being seen as a panacea for all; cost-utility analysis is hampered by uncertainties around accuracy of noninvasive biomarkers reflecting liver injury and a lack of effectiveness data for treatment. However, it seems reasonable to screen patients at high risk for NASH and adverse clinical outcomes. Such a risk stratification approach should be cost-effective.

A first key step by the PCP is to identify whether a patient is at risk, especially patients with NASH. The majority of patients at risk are already seen by PCPs. While there is no consensus on ideal screening for NAFLD by PCPs, the use of ultrasound in the at-risk population is recommended in Europe.⁴² Although NASH remains a histopathologic diagnosis, a reasonable approach is to define NASH based on clinical criteria as done similarly in a real-world observational NAFLD cohort study.⁵⁴ In the absence of chronic alcohol consumption and viral hepatitis and in a real-world scenario, NASH can be defined as steatosis shown on liver imaging or biopsy and alanine aminotransferase (ALT) levels of > 25 U/L. In addition, ≥ 1 of the following criteria must be met: BMI > 30, T2DM, dyslipidemia, or metabolic syndrome (Table 1). 

In the absence of easy-to-use validated tests, all patients with NAFLD need to be assessed with simple, noninvasive scores for the presence of clinically relevant liver fibrosis (F2-portal fibrosis with septa; F3-bridging fibrosis; F4-liver cirrhosis); those that meet the fibrosis criteria should receive further assessment usually only offered in a comprehensive NAFLD clinic.¹ PCPs should focus on addressing 2 aspects related to NAFLD: (1) Does my patient have NASH based on clinical criteria; and (2) Is my patient at risk for clinically relevant liver fibrosis? PCPs are integral in optimal management of comorbidities and metabolic syndrome abnormalities with lifestyle and exercise interventions.

The care needs of a typical patient with NAFLD can be classified into 3 categories: liver disease (NAFLD) management, addressing NAFLD associated comorbidities, and attending to the personal care needs of the patient. With considerable interactions between these categories, interventions done within the framework of 1 category can influence the needs pertaining to another, requiring closer monitoring of the patient and potentially modifying care. For example, initiating a low carbohydrate diet in a patient with DM and NAFLD who is on antidiabetic medication may require adjusting the medication; disease progression or failure to achieve treatment goals may affect the emotional state of the patient, which can affect adherence.

Referrals to a comprehensive NAFLD clinic need to be standardized. Clearly, the referral process depends in part on local resources, comprehensiveness of available services, and patient characteristics, among others. Most often, PCPs refer patients with suspected diagnosis of NAFLD, with or without abnormal aminotransferases, to a hepatologist to confirm the diagnosis and for disease staging and liver disease management. This may have the advantage of greatest extent of access and should limit the number of patients with advanced liver fibrosis who otherwise may have been missed. On the other hand, different thresholds of PCPs for referrals may delay the patient’s access to comprehensive NAFLD care. Of those referred by primary care, the hepatologist identifies patients with NAFLD who benefit most from a comprehensive care approach. This automated referral process without predefined criteria remains more a vision than reality as it would require an infrastructure and resources that no health care system can provide currently.

The alternative approach of automatic referral may use predefined criteria related to patients’ diagnoses and prognoses (Figure 2). 

Patient-Centered Care

At present the narrow focus of VHA specialty outpatient clinics associated with time constraints of providers and gaps in NAFLD awareness clearly does not address the complex metabolic needs of veterans with NAFLD. This is in striking contrast to the comprehensive care offered to patients with cancer. To overcome these limitations, new care delivery models need to be explored. At first it seems attractive to embed NAFLD patient care geographically into a hepatology clinic with the potential advantages of improving volume and timeliness of referral and reinforcing communication among specialty providers while maximizing convenience for patients. However, this is resource intensive not only concerning clinic space, but also in terms of staffing clinics with specialty providers.

Patient-centered care for veterans with NAFLD seems to be best organized around a comprehensive NAFLD clinic with access to specialized diagnostics and knowledge in day-to-day NAFLD management. This evolving care concept has been developed already for patients with liver cirrhosis and inflammatory bowel disease and considers NAFLD a chronic disease that cannot be addressed sufficiently by providing episodic care.^55,56 The development of comprehensive NAFLD care can build on the great success of the Hepatitis Innovation Team Collaborative that employed lean management strategies with local and regional teams to facilitate efforts to make chronic hepatitis C virus a rare disease in the VHA.⁵⁷

NAFLD Care Team

Given the central role of the liver and gastrointestinal tract in the field of nutrition, knowledge of the pathophysiology of the liver and digestive tract as well as emerging therapeutic options offered via metabolic endoscopy uniquely positions the hepatologist/gastroenterologist to take the lead in managing NAFLD. Treating NAFLD is best accomplished when the specialist partners with other health care providers who have expertise in the nutritional, behavioral, and physical activity aspects of treatment. The composition of the NAFLD care team and the roles that different providers fulfill can vary depending on the clinical setting; however, the hepatologist/gastroenterologist is best suited to lead the team, or alternatively, this role can be fulfilled by a provider with liver disease expertise.

Based on experiences from the United Kingdom, the minimum staffing of a NAFLD clinic should include a physician and nurse practitioner who has expertise in managing patients with chronic liver disease, a registered nurse, a dietitian, and a clinical pharmacy specialist (CPS).⁵⁸ With coexistent diseases common and many veterans who have > 5 prescribed medications, risk of polypharmacy and adverse drug reactions are a concern, particularly since adherence in patients with chronic diseases has been reported to be as low as 43%.^59-61 Risk of medication errors and serious adverse effects are magnified by difficulties with patient adherence, medication interactions, and potential need for frequent dose adjustments, particularly when on a weight-loss diet.

Without doubt, comprehensive medication management, offered by a highly trained CPS with independent prescriptive authority occurring while the veteran is in the NAFLD clinic, is highly desirable. Establishing a functional statement and care coordination agreement could describe the role of the CPS as a member of the NAFLD provider team. 

Patient Evaluation

After being referred to the NAFLD clinic, the veteran should have a thorough assessment, including medical, nutritional, physical activity, exercise, and psychosocial evaluations (Figure 4). 

The assessment also should include patient education to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals. Educating on NAFLD is critical as most patients with NAFLD do not think of themselves as sick and have limited readiness for lifestyle changes.^63,64 A better understanding of NAFLD combined with a higher self-efficacy seems to be positively linked to better nutritional habits.⁶⁵

An online patient-reported outcomes measurement information system for a patient with NAFLD (eg, assessmentcenter.net) may be beneficial and can be applied within a routine NAFLD clinic visit because of its multidimensionality and compatibility with other chronic diseases.^66-68 Other tools to assess health-related QOL include questionnaires, such as the functional assessment of chronic illness therapy-fatigue, work productivity and activity impairment questionnaire: specific health problem, Short Form-36, and chronic liver disease questionnaire-NAFLD.^23,69

The medical evaluation includes assessment of secondary causes of NAFLD and identification of NAFLD-related comorbidities. Weight, height, blood pressure, waist circumference, and BMI should be recorded. The physical exam should focus on signs of chronic liver disease and include inspection for acanthosis nigricans, hirsutism, and large neck circumference, which are associated with insulin resistance, polycystic ovarian syndrome, and obstructive sleep apnea, respectively. NAFLD-associated comorbidities may contribute to frailty or physical limitations that affect treatment with diet and exercise and need to be assessed. A thorough medication reconciliation will reveal whether the patient is prescribed obesogenic medications and whether comorbidities (eg, DM and dyslipidemia) are being treated optimally and according to current society guidelines.

Making the diagnosis of NAFLD requires excluding other (concomitant) chronic liver diseases. While often this is done indirectly using order sets with a panoply of available serologic tests without accounting for risks for rare causes of liver injury, a more focused and cost-effective approach is warranted. As most patients will already have had imaging studies that show fatty liver, assessment of liver fibrosis is an important step for risk stratification. Noninvasive scores (eg, FIB-4) can be used by the PCP to identify high-risk patients requiring further workup and referral.^1,70 More sophisticated tools, including transient elastography and/or magnetic resonance elastography are applied for more sophisticated risk stratification and liver disease management (Table 2).⁷¹ 

A nutritional evaluation includes information about eating behavior and food choices, body composition analysis, and an assessment of short- and long-term alcohol consumption. Presence of bilateral muscle wasting, subcutaneous fat loss, and signs of micronutrient deficiencies also should be explored. The lifestyle evaluation should include the patient’s typical physical activity and exercise as well as limiting factors.

Finally, and equally important, the patient’s psychosocial situation should be assessed, as motivation and accountability are key to success and may require behavioral modification. Assessing readiness is done best with motivational interviewing, the 5As counseling framework (Ask, Advise, Assess, Assist, Arrange) or using open-ended questions, affirmation, reflections, and summaries.^72,73 Even if not personally delivering behavioral treatment, such an approach also can help move patients toward addressing important health-related behaviors.

Personalized Interventions

If available, patients should be offered participation in NAFLD clinical trials. A personalized treatment plan should be developed for each patient with input from all NAFLD care team members. The patient and providers should work together to make important decisions about the treatment plan and goals of care. Making the patient an active participant in their treatment rather than the passive recipient will lead to improvement in adherence and outcomes. Patients will engage when they are comfortable speaking with providers and are sufficiently educated about their disease.

Personalized interventions may be built by combining different strategies, such as lifestyle and dietary interventions, NASH-specific pharmacotherapy, comorbidity management, metabolic endoscopy, and bariatric surgery. Although NASH-specific medications are not currently available, approved medications, including pioglitazone or liraglutide, can be considered for therapy.^74,75 Ideally, the NAFLD team CPS would manage comorbidities, such as T2DM and dyslipidemia, but this also can be done by a hepatologist or other specialist. Metabolic endoscopy (eg, intragastric balloons) or bariatric surgery would be done by referral.

Resource-Limited Settings

Although the VHA offers care at > 150 medical centers and > 1,000 outpatient clinics, specialty care such as hepatology and sophisticated and novel testing modalities are not available at many facilities. In 2011 VHA launched the Specialty Care Access Network Extension for Community Healthcare Outcomes to bring hepatitis C therapy and liver transplantation evaluations to rural areas without specialists.^76-78 It is logical to explore how telehealth can be used for NAFLD care that requires complex management using new treatments and has a high societal impact, particularly when left untreated.

Telehealth must be easy to use and integrated into everyday routines to be useful for NAFLD management by addressing different aspects of promoting self-management, optimizing therapy, and care coordination. Participation in a structured face-to-face or group-based lifestyle program is often jeopardized by time and job constraints but can be successfully overcome using online approaches.⁷⁹ The Internet-based VA Video Connect videoconferencing, which incorporates cell phone, laptop, or tablet use could help expand lifestyle interventions to a much larger community of patients with NAFLD and overcome local resource constraints. Finally, e-consultation also can be used in circumstances where synchronous communication with specialists may not be necessary.

Patient Monitoring and Quality Metrics

Monitoring of the patient after initiation of an intervention is variable but occurs more frequently at the beginning. For high-intensity dietary interventions, weekly monitoring for the first several weeks can ensure ongoing motivation, and accountability may increase the patient’s confidence and provide encouragement for further weight loss. It also is an opportunity to reestablish goals with patients with declining motivation. Long-term monitoring of patients may occur in 6- to 12-month intervals to document patient-reported outcomes, liver-related mortality, cardiovascular events, malignancies, and disease progression or regression.

While quality indicators have been proposed for cirrhosis care, such indicators have yet to be defined for NALD care.⁸⁰ Such quality indicators assessed with validated questionnaires should include knowledge about NAFLD, satisfaction with care, perception of quality of care, and patient-reported outcomes. Other indicators may include use of therapies to treat dyslipidemia and T2DM. Last and likely the most important indicator of improved liver health in NAFLD will be either histologic improvement of NASH or improvement of the fibrosis risk category.

Outlook

With the enormous burden of NAFLD on the rise for many more years to come, quality care delivered to patients with NAFLD warrants resource-adaptive population health management strategies. With a limited number of providers specialized in liver disease, provider education assisted by clinical guidelines and decision support tools, development of referral and access to care mechanisms through integrated care, remote monitoring strategies as well as development of patient self-management and community resources will become more important. We have outlined essential components of an effective population health management strategy for NAFLD and actionable items for the VHA to consider when implementing these strategies. This is the time for the VHA to invest in efforts for NAFLD population care. Clearly, consideration must be given to local needs and resources and integration of technology platforms. Addressing NAFLD at a population level will provide yet another opportunity to demonstrate that VHA performs better on quality when compared with care systems in the private sector.⁸¹

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers a spectrum of phenotypes ranging from nonalcoholic fatty liver or simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) defined by histologic findings of steatosis, lobular inflammation, cytologic ballooning, and some degree of fibrosis.¹ While frequently observed in patients with at least 1 risk factor (eg, obesity, diabetes mellitus [DM], dyslipidemia, hypertension), NAFLD also is an independent risk factor for type 2 DM (T2DM), chronic kidney disease, and cardiovascular disease.² At early disease stages with absence of liver fibrosis, mortality is linked to cardiovascular and not liver disease. However, in the presence of NASH, fibrosis progression to liver cirrhosis, or hepatocellular carcinoma (HCC) represent the most important liver-related outcomes that determine morbidity and mortality.³ Mirroring the obesity and T2DM epidemics, the health care burden is projected to dramatically rise.

In the following article, we will discuss how the Veterans Health Administration (VHA) is well positioned to implement an organizational strategy of comprehensive care for veterans with NAFLD. This comprehensive care strategy should include the development of a NAFLD clinic offering care for comorbid conditions frequently present in these patients, point-of-care testing, access to clinical trials, and outcomes monitoring as a key performance target for providers and the respective facility.

NAFLD disease burden

To fully appreciate the burden of a chronic disease like NAFLD, it is important to assess its long- and short-term consequences in a comprehensive manner with regard to its clinical impact, impact on the patient, and economic impact (Figure 1).

Clinical Impact

Clinical impact is assessed based on the prevalence and natural history of NAFLD and the liver fibrosis stage and determines patient survival. Coinciding with the epidemic of obesity and T2DM, the prevalence of NAFLD in the general population in North America is 24% and even higher with older age and higher body mass index (BMI).^4,5 The prevalence for NAFLD is particularly high in patients with T2DM (47%). Of patients with T2DM and NAFLD, 65% have biopsy-proven NASH of which 15% have bridging fibrosis or liver cirrhosis.⁶

NAFLD is the fastest growing cause of cirrhosis in the US with a forecasted NAFLD population of 101 million by 2030.⁷ At the same time, the number of patients with NASH will rise to 27 million of which > 7 million will have bridging fibrosis or liver cirrhosis; hepatic decompensation events are estimated to occur in 105,430 patients with liver cirrhosis, posing a major public health threat related to organ availability for liver transplantation.⁸ Since 2013, NAFLD has been the second leading cause for liver transplantation and the top reason for transplantation in patients aged < 50 years.^9,10 As many patients with NAFLD are diagnosed with HCC at stages where liver transplantation is not an option, mortality from HCC in NAFLD patients is higher than with other etiologies as treatment options are restricted.^11,12

Compared with that of the general population, veterans seeking care are older and sicker with 43% of veterans taking > 5 prescribed medications.¹³ Of those receiving VHA care, 6.6 million veterans are either overweight or obese; 165,000 are morbidly obese with a BMI > 40.¹⁴ In addition, veterans are 2.5 times more likely to have T2DM compared with that of nonveterans. Because T2DM and obesity are the most common risk factors for NAFLD, it is not surprising that NAFLD prevalence among veterans rose 3-fold from 2003 to 2011.¹⁵ It is now estimated that 540,000 veterans will progress to NASH and 108,000 will develop bridging fibrosis or liver cirrhosis by 2030.⁸ Similar to that of the general population, liver cirrhosis is attributed to NAFLD in 15% of veterans.^15,16 NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 years and 70 years, respectively.^16,17 Shockingly, 20% of HCCs were not linked to liver cirrhosis and escaped recommended HCC screening for patients with cirrhosis.^18,19

Patient Impact

Assessment of disease burden should not be restricted to clinical outcomes as patients can experience a range of symptoms that may have significant impact on their health-related quality of life (QOL) and functional status.²⁰ Using general but not disease-specific instruments, NAFLD patients reported outcomes score low regarding fatigue, activity, and emotions.²¹ More disease-specific questionnaires may provide better and disease-specific insights as how NASH impacts patients’ QOL.^22-24

Economic Impact

There is mounting evidence that the clinical implications of NAFLD directly influence the economic burden of NAFLD.²⁵ The annual burden associated with all incident and prevalent NAFLD cases in the US has been estimated at $103 billion, and projections suggest that the expected 10-year burden of NAFLD may increase to $1.005 trillion.²⁶ It is anticipated that increased NAFLD costs will affect the VHA with billions of dollars in annual expenditures in addition to the $1.5 billion already spent annually for T2DM care (4% of the VA pharmacy budget is spent on T2DM treatment).^27-29

Current Patient Care

Obesity, DM, and dyslipidemia are common conditions managed by primary care providers (PCPs). Given the close association of these conditions with NAFLD, the PCP is often the first point of medical contact for patients with or at risk for NAFLD.³⁰ For that reason, PCP awareness of NAFLD is critical for effective management of these patients. PCPs should be actively involved in the management of patients with NAFLD with pathways in place for identifying patients at high risk of liver disease for timely referral to a specialist and adequate education on the follow-up and treatment of low-risk patients. Instead, diagnosis of NAFLD is primarily triggered by either abnormal aminotransferases or detection of steatosis on imaging performed for other indications.

Barriers to optimal management of NAFLD by PCPs have been identified and occur at different levels of patient care. In the absence of clinical practice guidelines by the American Association of Family Practice covering NAFLD and a substantial latency period without signs of symptoms, NAFLD may not be perceived as a potentially serious condition by PCPs and their patients; interestingly this holds true even for some medical specialties.^31-39 More than half of PCPs do not test their patients at highest risk for NAFLD (eg, patients with obesity or T2DM) and may be unaware of practice guidelines.^40-42

Guidelines from Europe and the US are not completely in accordance. The US guidelines are vague regarding screening and are supported by only 1 medical society, due to the lack of NASH-specific drug therapies. The European guidelines are built on the support of 3 different stakeholders covering liver diseases, obesity, and DM and the experience using noninvasive liver fibrosis assessments for patients with NAFLD. To overcome this apparent conflict, a more practical and risk-stratified approach is warranted.^41,42

Making the diagnosis can be challenging in cases with competing etiologies, such as T2DM and alcohol misuse. There also is an overreliance on aminotransferase levels to diagnose NAFLD. Significant liver disease can exist in the presence of normal aminotransferases, and this may be attributed to either spontaneous aminotransferase fluctuations or upper limits of normal that have been chosen too high.^43-47 Often additional workup by PCPs depends on the magnitude of aminotransferase abnormalities.

Even if NAFLD has been diagnosed by PCPs, identifying those with NASH is hindered by the absence of an accurate noninvasive diagnostic method and the need to perform a liver biopsy. Liver biopsy is often not considered or delayed to monitor patients with serial aminotransferases, regardless of the patient’s metabolic comorbidity profile or baseline aminotransferases.³² As a result, referral to a specialist often depends on the magnitude of the aminotransferase abnormality,^30,48 and often occurs when advanced liver disease is already present.⁴⁹ Finally, providers may not be aware of beneficial effects of lifestyle interventions and certain medications, including statins on NASH and liver fibrosis.^50-53 As NAFLD is associated with excess cardiovascular- and cancer-related morbidity and mortality, it is possible that regression of NAFLD may improve associated risk for these outcomes as well.

Framework for Comprehensive NAFLD Care

Chronic liver diseases and associated comorbidities have long been addressed by PCPs and specialty providers working in isolation and within the narrow focus of each discipline. Contrary to working in silos of the past, a coordinated management strategy with other disciplines that cover these comorbidities needs to be established, or alternatively the PCP must be aware of the management of comorbidities to execute them independently. Integration of hepatology-driven NAFLD care with other specialties involves communication, collaboration, and sharing of resources and expertise that will address patient care needs. Obviously, this cannot be undertaken in a single outpatient visit and requires vertical and longitudinal follow-up over time. One important aspect of comprehensive NAFLD care is the targeting of a particular patient population rather than being seen as a panacea for all; cost-utility analysis is hampered by uncertainties around accuracy of noninvasive biomarkers reflecting liver injury and a lack of effectiveness data for treatment. However, it seems reasonable to screen patients at high risk for NASH and adverse clinical outcomes. Such a risk stratification approach should be cost-effective.

A first key step by the PCP is to identify whether a patient is at risk, especially patients with NASH. The majority of patients at risk are already seen by PCPs. While there is no consensus on ideal screening for NAFLD by PCPs, the use of ultrasound in the at-risk population is recommended in Europe.⁴² Although NASH remains a histopathologic diagnosis, a reasonable approach is to define NASH based on clinical criteria as done similarly in a real-world observational NAFLD cohort study.⁵⁴ In the absence of chronic alcohol consumption and viral hepatitis and in a real-world scenario, NASH can be defined as steatosis shown on liver imaging or biopsy and alanine aminotransferase (ALT) levels of > 25 U/L. In addition, ≥ 1 of the following criteria must be met: BMI > 30, T2DM, dyslipidemia, or metabolic syndrome (Table 1). 

In the absence of easy-to-use validated tests, all patients with NAFLD need to be assessed with simple, noninvasive scores for the presence of clinically relevant liver fibrosis (F2-portal fibrosis with septa; F3-bridging fibrosis; F4-liver cirrhosis); those that meet the fibrosis criteria should receive further assessment usually only offered in a comprehensive NAFLD clinic.¹ PCPs should focus on addressing 2 aspects related to NAFLD: (1) Does my patient have NASH based on clinical criteria; and (2) Is my patient at risk for clinically relevant liver fibrosis? PCPs are integral in optimal management of comorbidities and metabolic syndrome abnormalities with lifestyle and exercise interventions.

The care needs of a typical patient with NAFLD can be classified into 3 categories: liver disease (NAFLD) management, addressing NAFLD associated comorbidities, and attending to the personal care needs of the patient. With considerable interactions between these categories, interventions done within the framework of 1 category can influence the needs pertaining to another, requiring closer monitoring of the patient and potentially modifying care. For example, initiating a low carbohydrate diet in a patient with DM and NAFLD who is on antidiabetic medication may require adjusting the medication; disease progression or failure to achieve treatment goals may affect the emotional state of the patient, which can affect adherence.

Referrals to a comprehensive NAFLD clinic need to be standardized. Clearly, the referral process depends in part on local resources, comprehensiveness of available services, and patient characteristics, among others. Most often, PCPs refer patients with suspected diagnosis of NAFLD, with or without abnormal aminotransferases, to a hepatologist to confirm the diagnosis and for disease staging and liver disease management. This may have the advantage of greatest extent of access and should limit the number of patients with advanced liver fibrosis who otherwise may have been missed. On the other hand, different thresholds of PCPs for referrals may delay the patient’s access to comprehensive NAFLD care. Of those referred by primary care, the hepatologist identifies patients with NAFLD who benefit most from a comprehensive care approach. This automated referral process without predefined criteria remains more a vision than reality as it would require an infrastructure and resources that no health care system can provide currently.

The alternative approach of automatic referral may use predefined criteria related to patients’ diagnoses and prognoses (Figure 2). 

Patient-Centered Care

At present the narrow focus of VHA specialty outpatient clinics associated with time constraints of providers and gaps in NAFLD awareness clearly does not address the complex metabolic needs of veterans with NAFLD. This is in striking contrast to the comprehensive care offered to patients with cancer. To overcome these limitations, new care delivery models need to be explored. At first it seems attractive to embed NAFLD patient care geographically into a hepatology clinic with the potential advantages of improving volume and timeliness of referral and reinforcing communication among specialty providers while maximizing convenience for patients. However, this is resource intensive not only concerning clinic space, but also in terms of staffing clinics with specialty providers.

Patient-centered care for veterans with NAFLD seems to be best organized around a comprehensive NAFLD clinic with access to specialized diagnostics and knowledge in day-to-day NAFLD management. This evolving care concept has been developed already for patients with liver cirrhosis and inflammatory bowel disease and considers NAFLD a chronic disease that cannot be addressed sufficiently by providing episodic care.^55,56 The development of comprehensive NAFLD care can build on the great success of the Hepatitis Innovation Team Collaborative that employed lean management strategies with local and regional teams to facilitate efforts to make chronic hepatitis C virus a rare disease in the VHA.⁵⁷

NAFLD Care Team

Given the central role of the liver and gastrointestinal tract in the field of nutrition, knowledge of the pathophysiology of the liver and digestive tract as well as emerging therapeutic options offered via metabolic endoscopy uniquely positions the hepatologist/gastroenterologist to take the lead in managing NAFLD. Treating NAFLD is best accomplished when the specialist partners with other health care providers who have expertise in the nutritional, behavioral, and physical activity aspects of treatment. The composition of the NAFLD care team and the roles that different providers fulfill can vary depending on the clinical setting; however, the hepatologist/gastroenterologist is best suited to lead the team, or alternatively, this role can be fulfilled by a provider with liver disease expertise.

Based on experiences from the United Kingdom, the minimum staffing of a NAFLD clinic should include a physician and nurse practitioner who has expertise in managing patients with chronic liver disease, a registered nurse, a dietitian, and a clinical pharmacy specialist (CPS).⁵⁸ With coexistent diseases common and many veterans who have > 5 prescribed medications, risk of polypharmacy and adverse drug reactions are a concern, particularly since adherence in patients with chronic diseases has been reported to be as low as 43%.^59-61 Risk of medication errors and serious adverse effects are magnified by difficulties with patient adherence, medication interactions, and potential need for frequent dose adjustments, particularly when on a weight-loss diet.

Without doubt, comprehensive medication management, offered by a highly trained CPS with independent prescriptive authority occurring while the veteran is in the NAFLD clinic, is highly desirable. Establishing a functional statement and care coordination agreement could describe the role of the CPS as a member of the NAFLD provider team. 

Patient Evaluation

After being referred to the NAFLD clinic, the veteran should have a thorough assessment, including medical, nutritional, physical activity, exercise, and psychosocial evaluations (Figure 4). 

The assessment also should include patient education to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals. Educating on NAFLD is critical as most patients with NAFLD do not think of themselves as sick and have limited readiness for lifestyle changes.^63,64 A better understanding of NAFLD combined with a higher self-efficacy seems to be positively linked to better nutritional habits.⁶⁵

An online patient-reported outcomes measurement information system for a patient with NAFLD (eg, assessmentcenter.net) may be beneficial and can be applied within a routine NAFLD clinic visit because of its multidimensionality and compatibility with other chronic diseases.^66-68 Other tools to assess health-related QOL include questionnaires, such as the functional assessment of chronic illness therapy-fatigue, work productivity and activity impairment questionnaire: specific health problem, Short Form-36, and chronic liver disease questionnaire-NAFLD.^23,69

The medical evaluation includes assessment of secondary causes of NAFLD and identification of NAFLD-related comorbidities. Weight, height, blood pressure, waist circumference, and BMI should be recorded. The physical exam should focus on signs of chronic liver disease and include inspection for acanthosis nigricans, hirsutism, and large neck circumference, which are associated with insulin resistance, polycystic ovarian syndrome, and obstructive sleep apnea, respectively. NAFLD-associated comorbidities may contribute to frailty or physical limitations that affect treatment with diet and exercise and need to be assessed. A thorough medication reconciliation will reveal whether the patient is prescribed obesogenic medications and whether comorbidities (eg, DM and dyslipidemia) are being treated optimally and according to current society guidelines.

Making the diagnosis of NAFLD requires excluding other (concomitant) chronic liver diseases. While often this is done indirectly using order sets with a panoply of available serologic tests without accounting for risks for rare causes of liver injury, a more focused and cost-effective approach is warranted. As most patients will already have had imaging studies that show fatty liver, assessment of liver fibrosis is an important step for risk stratification. Noninvasive scores (eg, FIB-4) can be used by the PCP to identify high-risk patients requiring further workup and referral.^1,70 More sophisticated tools, including transient elastography and/or magnetic resonance elastography are applied for more sophisticated risk stratification and liver disease management (Table 2).⁷¹ 

A nutritional evaluation includes information about eating behavior and food choices, body composition analysis, and an assessment of short- and long-term alcohol consumption. Presence of bilateral muscle wasting, subcutaneous fat loss, and signs of micronutrient deficiencies also should be explored. The lifestyle evaluation should include the patient’s typical physical activity and exercise as well as limiting factors.

Finally, and equally important, the patient’s psychosocial situation should be assessed, as motivation and accountability are key to success and may require behavioral modification. Assessing readiness is done best with motivational interviewing, the 5As counseling framework (Ask, Advise, Assess, Assist, Arrange) or using open-ended questions, affirmation, reflections, and summaries.^72,73 Even if not personally delivering behavioral treatment, such an approach also can help move patients toward addressing important health-related behaviors.

Personalized Interventions

If available, patients should be offered participation in NAFLD clinical trials. A personalized treatment plan should be developed for each patient with input from all NAFLD care team members. The patient and providers should work together to make important decisions about the treatment plan and goals of care. Making the patient an active participant in their treatment rather than the passive recipient will lead to improvement in adherence and outcomes. Patients will engage when they are comfortable speaking with providers and are sufficiently educated about their disease.

Personalized interventions may be built by combining different strategies, such as lifestyle and dietary interventions, NASH-specific pharmacotherapy, comorbidity management, metabolic endoscopy, and bariatric surgery. Although NASH-specific medications are not currently available, approved medications, including pioglitazone or liraglutide, can be considered for therapy.^74,75 Ideally, the NAFLD team CPS would manage comorbidities, such as T2DM and dyslipidemia, but this also can be done by a hepatologist or other specialist. Metabolic endoscopy (eg, intragastric balloons) or bariatric surgery would be done by referral.

Resource-Limited Settings

Although the VHA offers care at > 150 medical centers and > 1,000 outpatient clinics, specialty care such as hepatology and sophisticated and novel testing modalities are not available at many facilities. In 2011 VHA launched the Specialty Care Access Network Extension for Community Healthcare Outcomes to bring hepatitis C therapy and liver transplantation evaluations to rural areas without specialists.^76-78 It is logical to explore how telehealth can be used for NAFLD care that requires complex management using new treatments and has a high societal impact, particularly when left untreated.

Telehealth must be easy to use and integrated into everyday routines to be useful for NAFLD management by addressing different aspects of promoting self-management, optimizing therapy, and care coordination. Participation in a structured face-to-face or group-based lifestyle program is often jeopardized by time and job constraints but can be successfully overcome using online approaches.⁷⁹ The Internet-based VA Video Connect videoconferencing, which incorporates cell phone, laptop, or tablet use could help expand lifestyle interventions to a much larger community of patients with NAFLD and overcome local resource constraints. Finally, e-consultation also can be used in circumstances where synchronous communication with specialists may not be necessary.

Patient Monitoring and Quality Metrics

Monitoring of the patient after initiation of an intervention is variable but occurs more frequently at the beginning. For high-intensity dietary interventions, weekly monitoring for the first several weeks can ensure ongoing motivation, and accountability may increase the patient’s confidence and provide encouragement for further weight loss. It also is an opportunity to reestablish goals with patients with declining motivation. Long-term monitoring of patients may occur in 6- to 12-month intervals to document patient-reported outcomes, liver-related mortality, cardiovascular events, malignancies, and disease progression or regression.

While quality indicators have been proposed for cirrhosis care, such indicators have yet to be defined for NALD care.⁸⁰ Such quality indicators assessed with validated questionnaires should include knowledge about NAFLD, satisfaction with care, perception of quality of care, and patient-reported outcomes. Other indicators may include use of therapies to treat dyslipidemia and T2DM. Last and likely the most important indicator of improved liver health in NAFLD will be either histologic improvement of NASH or improvement of the fibrosis risk category.

Outlook

With the enormous burden of NAFLD on the rise for many more years to come, quality care delivered to patients with NAFLD warrants resource-adaptive population health management strategies. With a limited number of providers specialized in liver disease, provider education assisted by clinical guidelines and decision support tools, development of referral and access to care mechanisms through integrated care, remote monitoring strategies as well as development of patient self-management and community resources will become more important. We have outlined essential components of an effective population health management strategy for NAFLD and actionable items for the VHA to consider when implementing these strategies. This is the time for the VHA to invest in efforts for NAFLD population care. Clearly, consideration must be given to local needs and resources and integration of technology platforms. Addressing NAFLD at a population level will provide yet another opportunity to demonstrate that VHA performs better on quality when compared with care systems in the private sector.⁸¹

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers a spectrum of phenotypes ranging from nonalcoholic fatty liver or simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) defined by histologic findings of steatosis, lobular inflammation, cytologic ballooning, and some degree of fibrosis.¹ While frequently observed in patients with at least 1 risk factor (eg, obesity, diabetes mellitus [DM], dyslipidemia, hypertension), NAFLD also is an independent risk factor for type 2 DM (T2DM), chronic kidney disease, and cardiovascular disease.² At early disease stages with absence of liver fibrosis, mortality is linked to cardiovascular and not liver disease. However, in the presence of NASH, fibrosis progression to liver cirrhosis, or hepatocellular carcinoma (HCC) represent the most important liver-related outcomes that determine morbidity and mortality.³ Mirroring the obesity and T2DM epidemics, the health care burden is projected to dramatically rise.

In the following article, we will discuss how the Veterans Health Administration (VHA) is well positioned to implement an organizational strategy of comprehensive care for veterans with NAFLD. This comprehensive care strategy should include the development of a NAFLD clinic offering care for comorbid conditions frequently present in these patients, point-of-care testing, access to clinical trials, and outcomes monitoring as a key performance target for providers and the respective facility.

NAFLD disease burden

To fully appreciate the burden of a chronic disease like NAFLD, it is important to assess its long- and short-term consequences in a comprehensive manner with regard to its clinical impact, impact on the patient, and economic impact (Figure 1).

Clinical Impact

Clinical impact is assessed based on the prevalence and natural history of NAFLD and the liver fibrosis stage and determines patient survival. Coinciding with the epidemic of obesity and T2DM, the prevalence of NAFLD in the general population in North America is 24% and even higher with older age and higher body mass index (BMI).^4,5 The prevalence for NAFLD is particularly high in patients with T2DM (47%). Of patients with T2DM and NAFLD, 65% have biopsy-proven NASH of which 15% have bridging fibrosis or liver cirrhosis.⁶

NAFLD is the fastest growing cause of cirrhosis in the US with a forecasted NAFLD population of 101 million by 2030.⁷ At the same time, the number of patients with NASH will rise to 27 million of which > 7 million will have bridging fibrosis or liver cirrhosis; hepatic decompensation events are estimated to occur in 105,430 patients with liver cirrhosis, posing a major public health threat related to organ availability for liver transplantation.⁸ Since 2013, NAFLD has been the second leading cause for liver transplantation and the top reason for transplantation in patients aged < 50 years.^9,10 As many patients with NAFLD are diagnosed with HCC at stages where liver transplantation is not an option, mortality from HCC in NAFLD patients is higher than with other etiologies as treatment options are restricted.^11,12

Compared with that of the general population, veterans seeking care are older and sicker with 43% of veterans taking > 5 prescribed medications.¹³ Of those receiving VHA care, 6.6 million veterans are either overweight or obese; 165,000 are morbidly obese with a BMI > 40.¹⁴ In addition, veterans are 2.5 times more likely to have T2DM compared with that of nonveterans. Because T2DM and obesity are the most common risk factors for NAFLD, it is not surprising that NAFLD prevalence among veterans rose 3-fold from 2003 to 2011.¹⁵ It is now estimated that 540,000 veterans will progress to NASH and 108,000 will develop bridging fibrosis or liver cirrhosis by 2030.⁸ Similar to that of the general population, liver cirrhosis is attributed to NAFLD in 15% of veterans.^15,16 NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 years and 70 years, respectively.^16,17 Shockingly, 20% of HCCs were not linked to liver cirrhosis and escaped recommended HCC screening for patients with cirrhosis.^18,19

Patient Impact

Assessment of disease burden should not be restricted to clinical outcomes as patients can experience a range of symptoms that may have significant impact on their health-related quality of life (QOL) and functional status.²⁰ Using general but not disease-specific instruments, NAFLD patients reported outcomes score low regarding fatigue, activity, and emotions.²¹ More disease-specific questionnaires may provide better and disease-specific insights as how NASH impacts patients’ QOL.^22-24

Economic Impact

There is mounting evidence that the clinical implications of NAFLD directly influence the economic burden of NAFLD.²⁵ The annual burden associated with all incident and prevalent NAFLD cases in the US has been estimated at $103 billion, and projections suggest that the expected 10-year burden of NAFLD may increase to $1.005 trillion.²⁶ It is anticipated that increased NAFLD costs will affect the VHA with billions of dollars in annual expenditures in addition to the $1.5 billion already spent annually for T2DM care (4% of the VA pharmacy budget is spent on T2DM treatment).^27-29

Current Patient Care

Obesity, DM, and dyslipidemia are common conditions managed by primary care providers (PCPs). Given the close association of these conditions with NAFLD, the PCP is often the first point of medical contact for patients with or at risk for NAFLD.³⁰ For that reason, PCP awareness of NAFLD is critical for effective management of these patients. PCPs should be actively involved in the management of patients with NAFLD with pathways in place for identifying patients at high risk of liver disease for timely referral to a specialist and adequate education on the follow-up and treatment of low-risk patients. Instead, diagnosis of NAFLD is primarily triggered by either abnormal aminotransferases or detection of steatosis on imaging performed for other indications.

Barriers to optimal management of NAFLD by PCPs have been identified and occur at different levels of patient care. In the absence of clinical practice guidelines by the American Association of Family Practice covering NAFLD and a substantial latency period without signs of symptoms, NAFLD may not be perceived as a potentially serious condition by PCPs and their patients; interestingly this holds true even for some medical specialties.^31-39 More than half of PCPs do not test their patients at highest risk for NAFLD (eg, patients with obesity or T2DM) and may be unaware of practice guidelines.^40-42

Guidelines from Europe and the US are not completely in accordance. The US guidelines are vague regarding screening and are supported by only 1 medical society, due to the lack of NASH-specific drug therapies. The European guidelines are built on the support of 3 different stakeholders covering liver diseases, obesity, and DM and the experience using noninvasive liver fibrosis assessments for patients with NAFLD. To overcome this apparent conflict, a more practical and risk-stratified approach is warranted.^41,42

Making the diagnosis can be challenging in cases with competing etiologies, such as T2DM and alcohol misuse. There also is an overreliance on aminotransferase levels to diagnose NAFLD. Significant liver disease can exist in the presence of normal aminotransferases, and this may be attributed to either spontaneous aminotransferase fluctuations or upper limits of normal that have been chosen too high.^43-47 Often additional workup by PCPs depends on the magnitude of aminotransferase abnormalities.

Even if NAFLD has been diagnosed by PCPs, identifying those with NASH is hindered by the absence of an accurate noninvasive diagnostic method and the need to perform a liver biopsy. Liver biopsy is often not considered or delayed to monitor patients with serial aminotransferases, regardless of the patient’s metabolic comorbidity profile or baseline aminotransferases.³² As a result, referral to a specialist often depends on the magnitude of the aminotransferase abnormality,^30,48 and often occurs when advanced liver disease is already present.⁴⁹ Finally, providers may not be aware of beneficial effects of lifestyle interventions and certain medications, including statins on NASH and liver fibrosis.^50-53 As NAFLD is associated with excess cardiovascular- and cancer-related morbidity and mortality, it is possible that regression of NAFLD may improve associated risk for these outcomes as well.

Framework for Comprehensive NAFLD Care

Chronic liver diseases and associated comorbidities have long been addressed by PCPs and specialty providers working in isolation and within the narrow focus of each discipline. Contrary to working in silos of the past, a coordinated management strategy with other disciplines that cover these comorbidities needs to be established, or alternatively the PCP must be aware of the management of comorbidities to execute them independently. Integration of hepatology-driven NAFLD care with other specialties involves communication, collaboration, and sharing of resources and expertise that will address patient care needs. Obviously, this cannot be undertaken in a single outpatient visit and requires vertical and longitudinal follow-up over time. One important aspect of comprehensive NAFLD care is the targeting of a particular patient population rather than being seen as a panacea for all; cost-utility analysis is hampered by uncertainties around accuracy of noninvasive biomarkers reflecting liver injury and a lack of effectiveness data for treatment. However, it seems reasonable to screen patients at high risk for NASH and adverse clinical outcomes. Such a risk stratification approach should be cost-effective.

A first key step by the PCP is to identify whether a patient is at risk, especially patients with NASH. The majority of patients at risk are already seen by PCPs. While there is no consensus on ideal screening for NAFLD by PCPs, the use of ultrasound in the at-risk population is recommended in Europe.⁴² Although NASH remains a histopathologic diagnosis, a reasonable approach is to define NASH based on clinical criteria as done similarly in a real-world observational NAFLD cohort study.⁵⁴ In the absence of chronic alcohol consumption and viral hepatitis and in a real-world scenario, NASH can be defined as steatosis shown on liver imaging or biopsy and alanine aminotransferase (ALT) levels of > 25 U/L. In addition, ≥ 1 of the following criteria must be met: BMI > 30, T2DM, dyslipidemia, or metabolic syndrome (Table 1). 

In the absence of easy-to-use validated tests, all patients with NAFLD need to be assessed with simple, noninvasive scores for the presence of clinically relevant liver fibrosis (F2-portal fibrosis with septa; F3-bridging fibrosis; F4-liver cirrhosis); those that meet the fibrosis criteria should receive further assessment usually only offered in a comprehensive NAFLD clinic.¹ PCPs should focus on addressing 2 aspects related to NAFLD: (1) Does my patient have NASH based on clinical criteria; and (2) Is my patient at risk for clinically relevant liver fibrosis? PCPs are integral in optimal management of comorbidities and metabolic syndrome abnormalities with lifestyle and exercise interventions.

The care needs of a typical patient with NAFLD can be classified into 3 categories: liver disease (NAFLD) management, addressing NAFLD associated comorbidities, and attending to the personal care needs of the patient. With considerable interactions between these categories, interventions done within the framework of 1 category can influence the needs pertaining to another, requiring closer monitoring of the patient and potentially modifying care. For example, initiating a low carbohydrate diet in a patient with DM and NAFLD who is on antidiabetic medication may require adjusting the medication; disease progression or failure to achieve treatment goals may affect the emotional state of the patient, which can affect adherence.

Referrals to a comprehensive NAFLD clinic need to be standardized. Clearly, the referral process depends in part on local resources, comprehensiveness of available services, and patient characteristics, among others. Most often, PCPs refer patients with suspected diagnosis of NAFLD, with or without abnormal aminotransferases, to a hepatologist to confirm the diagnosis and for disease staging and liver disease management. This may have the advantage of greatest extent of access and should limit the number of patients with advanced liver fibrosis who otherwise may have been missed. On the other hand, different thresholds of PCPs for referrals may delay the patient’s access to comprehensive NAFLD care. Of those referred by primary care, the hepatologist identifies patients with NAFLD who benefit most from a comprehensive care approach. This automated referral process without predefined criteria remains more a vision than reality as it would require an infrastructure and resources that no health care system can provide currently.

The alternative approach of automatic referral may use predefined criteria related to patients’ diagnoses and prognoses (Figure 2). 

Patient-Centered Care

At present the narrow focus of VHA specialty outpatient clinics associated with time constraints of providers and gaps in NAFLD awareness clearly does not address the complex metabolic needs of veterans with NAFLD. This is in striking contrast to the comprehensive care offered to patients with cancer. To overcome these limitations, new care delivery models need to be explored. At first it seems attractive to embed NAFLD patient care geographically into a hepatology clinic with the potential advantages of improving volume and timeliness of referral and reinforcing communication among specialty providers while maximizing convenience for patients. However, this is resource intensive not only concerning clinic space, but also in terms of staffing clinics with specialty providers.

Patient-centered care for veterans with NAFLD seems to be best organized around a comprehensive NAFLD clinic with access to specialized diagnostics and knowledge in day-to-day NAFLD management. This evolving care concept has been developed already for patients with liver cirrhosis and inflammatory bowel disease and considers NAFLD a chronic disease that cannot be addressed sufficiently by providing episodic care.^55,56 The development of comprehensive NAFLD care can build on the great success of the Hepatitis Innovation Team Collaborative that employed lean management strategies with local and regional teams to facilitate efforts to make chronic hepatitis C virus a rare disease in the VHA.⁵⁷

NAFLD Care Team

Given the central role of the liver and gastrointestinal tract in the field of nutrition, knowledge of the pathophysiology of the liver and digestive tract as well as emerging therapeutic options offered via metabolic endoscopy uniquely positions the hepatologist/gastroenterologist to take the lead in managing NAFLD. Treating NAFLD is best accomplished when the specialist partners with other health care providers who have expertise in the nutritional, behavioral, and physical activity aspects of treatment. The composition of the NAFLD care team and the roles that different providers fulfill can vary depending on the clinical setting; however, the hepatologist/gastroenterologist is best suited to lead the team, or alternatively, this role can be fulfilled by a provider with liver disease expertise.

Based on experiences from the United Kingdom, the minimum staffing of a NAFLD clinic should include a physician and nurse practitioner who has expertise in managing patients with chronic liver disease, a registered nurse, a dietitian, and a clinical pharmacy specialist (CPS).⁵⁸ With coexistent diseases common and many veterans who have > 5 prescribed medications, risk of polypharmacy and adverse drug reactions are a concern, particularly since adherence in patients with chronic diseases has been reported to be as low as 43%.^59-61 Risk of medication errors and serious adverse effects are magnified by difficulties with patient adherence, medication interactions, and potential need for frequent dose adjustments, particularly when on a weight-loss diet.

Without doubt, comprehensive medication management, offered by a highly trained CPS with independent prescriptive authority occurring while the veteran is in the NAFLD clinic, is highly desirable. Establishing a functional statement and care coordination agreement could describe the role of the CPS as a member of the NAFLD provider team. 

Patient Evaluation

After being referred to the NAFLD clinic, the veteran should have a thorough assessment, including medical, nutritional, physical activity, exercise, and psychosocial evaluations (Figure 4). 

The assessment also should include patient education to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals. Educating on NAFLD is critical as most patients with NAFLD do not think of themselves as sick and have limited readiness for lifestyle changes.^63,64 A better understanding of NAFLD combined with a higher self-efficacy seems to be positively linked to better nutritional habits.⁶⁵

An online patient-reported outcomes measurement information system for a patient with NAFLD (eg, assessmentcenter.net) may be beneficial and can be applied within a routine NAFLD clinic visit because of its multidimensionality and compatibility with other chronic diseases.^66-68 Other tools to assess health-related QOL include questionnaires, such as the functional assessment of chronic illness therapy-fatigue, work productivity and activity impairment questionnaire: specific health problem, Short Form-36, and chronic liver disease questionnaire-NAFLD.^23,69

The medical evaluation includes assessment of secondary causes of NAFLD and identification of NAFLD-related comorbidities. Weight, height, blood pressure, waist circumference, and BMI should be recorded. The physical exam should focus on signs of chronic liver disease and include inspection for acanthosis nigricans, hirsutism, and large neck circumference, which are associated with insulin resistance, polycystic ovarian syndrome, and obstructive sleep apnea, respectively. NAFLD-associated comorbidities may contribute to frailty or physical limitations that affect treatment with diet and exercise and need to be assessed. A thorough medication reconciliation will reveal whether the patient is prescribed obesogenic medications and whether comorbidities (eg, DM and dyslipidemia) are being treated optimally and according to current society guidelines.

Making the diagnosis of NAFLD requires excluding other (concomitant) chronic liver diseases. While often this is done indirectly using order sets with a panoply of available serologic tests without accounting for risks for rare causes of liver injury, a more focused and cost-effective approach is warranted. As most patients will already have had imaging studies that show fatty liver, assessment of liver fibrosis is an important step for risk stratification. Noninvasive scores (eg, FIB-4) can be used by the PCP to identify high-risk patients requiring further workup and referral.^1,70 More sophisticated tools, including transient elastography and/or magnetic resonance elastography are applied for more sophisticated risk stratification and liver disease management (Table 2).⁷¹ 

A nutritional evaluation includes information about eating behavior and food choices, body composition analysis, and an assessment of short- and long-term alcohol consumption. Presence of bilateral muscle wasting, subcutaneous fat loss, and signs of micronutrient deficiencies also should be explored. The lifestyle evaluation should include the patient’s typical physical activity and exercise as well as limiting factors.

Finally, and equally important, the patient’s psychosocial situation should be assessed, as motivation and accountability are key to success and may require behavioral modification. Assessing readiness is done best with motivational interviewing, the 5As counseling framework (Ask, Advise, Assess, Assist, Arrange) or using open-ended questions, affirmation, reflections, and summaries.^72,73 Even if not personally delivering behavioral treatment, such an approach also can help move patients toward addressing important health-related behaviors.

Personalized Interventions

If available, patients should be offered participation in NAFLD clinical trials. A personalized treatment plan should be developed for each patient with input from all NAFLD care team members. The patient and providers should work together to make important decisions about the treatment plan and goals of care. Making the patient an active participant in their treatment rather than the passive recipient will lead to improvement in adherence and outcomes. Patients will engage when they are comfortable speaking with providers and are sufficiently educated about their disease.

Personalized interventions may be built by combining different strategies, such as lifestyle and dietary interventions, NASH-specific pharmacotherapy, comorbidity management, metabolic endoscopy, and bariatric surgery. Although NASH-specific medications are not currently available, approved medications, including pioglitazone or liraglutide, can be considered for therapy.^74,75 Ideally, the NAFLD team CPS would manage comorbidities, such as T2DM and dyslipidemia, but this also can be done by a hepatologist or other specialist. Metabolic endoscopy (eg, intragastric balloons) or bariatric surgery would be done by referral.

Resource-Limited Settings

Although the VHA offers care at > 150 medical centers and > 1,000 outpatient clinics, specialty care such as hepatology and sophisticated and novel testing modalities are not available at many facilities. In 2011 VHA launched the Specialty Care Access Network Extension for Community Healthcare Outcomes to bring hepatitis C therapy and liver transplantation evaluations to rural areas without specialists.^76-78 It is logical to explore how telehealth can be used for NAFLD care that requires complex management using new treatments and has a high societal impact, particularly when left untreated.

Telehealth must be easy to use and integrated into everyday routines to be useful for NAFLD management by addressing different aspects of promoting self-management, optimizing therapy, and care coordination. Participation in a structured face-to-face or group-based lifestyle program is often jeopardized by time and job constraints but can be successfully overcome using online approaches.⁷⁹ The Internet-based VA Video Connect videoconferencing, which incorporates cell phone, laptop, or tablet use could help expand lifestyle interventions to a much larger community of patients with NAFLD and overcome local resource constraints. Finally, e-consultation also can be used in circumstances where synchronous communication with specialists may not be necessary.

Patient Monitoring and Quality Metrics

Monitoring of the patient after initiation of an intervention is variable but occurs more frequently at the beginning. For high-intensity dietary interventions, weekly monitoring for the first several weeks can ensure ongoing motivation, and accountability may increase the patient’s confidence and provide encouragement for further weight loss. It also is an opportunity to reestablish goals with patients with declining motivation. Long-term monitoring of patients may occur in 6- to 12-month intervals to document patient-reported outcomes, liver-related mortality, cardiovascular events, malignancies, and disease progression or regression.

While quality indicators have been proposed for cirrhosis care, such indicators have yet to be defined for NALD care.⁸⁰ Such quality indicators assessed with validated questionnaires should include knowledge about NAFLD, satisfaction with care, perception of quality of care, and patient-reported outcomes. Other indicators may include use of therapies to treat dyslipidemia and T2DM. Last and likely the most important indicator of improved liver health in NAFLD will be either histologic improvement of NASH or improvement of the fibrosis risk category.

Outlook

With the enormous burden of NAFLD on the rise for many more years to come, quality care delivered to patients with NAFLD warrants resource-adaptive population health management strategies. With a limited number of providers specialized in liver disease, provider education assisted by clinical guidelines and decision support tools, development of referral and access to care mechanisms through integrated care, remote monitoring strategies as well as development of patient self-management and community resources will become more important. We have outlined essential components of an effective population health management strategy for NAFLD and actionable items for the VHA to consider when implementing these strategies. This is the time for the VHA to invest in efforts for NAFLD population care. Clearly, consideration must be given to local needs and resources and integration of technology platforms. Addressing NAFLD at a population level will provide yet another opportunity to demonstrate that VHA performs better on quality when compared with care systems in the private sector.⁸¹

Oxygen is a highly effective treatment for cluster headache with few complications, according to patient survey results published in the February issue of Headache. According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.

To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.

In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).

Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.

Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.

“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”

Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.

Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.

The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.

This article was updated 3/7/2019.

[email protected]

SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.

Oxygen is a highly effective treatment for cluster headache with few complications, according to patient survey results published in the February issue of Headache. According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.

To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.

In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).

Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.

Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.

“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”

Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.

Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.

The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.

This article was updated 3/7/2019.

[email protected]

SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.

Oxygen is a highly effective treatment for cluster headache with few complications, according to patient survey results published in the February issue of Headache. According to the results, triptans also are highly effective, with some side effects. Newer medications deserve further study, the researchers said.

To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, Stuart M. Pearson, a researcher in the department of psychology at the University of West Georgia in Carrollton, and his coauthors analyzed data from the Cluster Headache Questionnaire. Respondents from more than 50 countries completed the online survey; most were from the United States, the United Kingdom, and Canada. The survey included questions about cluster headache diagnostic criteria and medication effectiveness, complications, and access to medications.

In all, 3,251 subjects participated in the questionnaire, and 2,193 respondents met criteria for the study; 1,604 had cluster headache, and 589 had probable cluster headache. Among the respondents with cluster headache, 68.8% were male, 78.0% had episodic cluster headache, and the average age was 46 years. More than half of respondents reported complete or very effective treatment for triptans (54%) and oxygen (also 54%). The proportion of respondents who reported that ergot derivatives, caffeine or energy drinks, and intranasal ketamine were completely or very effective ranged from 14% to 25%. Patients were less likely to report high levels of efficacy for opioids (6%), intranasal capsaicin (5%), and intranasal lidocaine (2%).

Participants experienced few complications from oxygen, with 99% reporting no or minimal physical and medical complications, and 97% reporting no or minimal psychological and emotional complications. Patients also reported few complications from intranasal lidocaine, intranasal ketamine, intranasal capsaicin, and caffeine and energy drinks. For triptans, 74% of respondents reported no or minimal physical and medical complications, and 85% reported no or minimal psychological and emotional complications.

Among the 139 participants with cluster headache who were aged 65 years or older, responses were similar to those for the entire population. In addition, the 589 respondents with probable cluster headache reported similar efficacy data, compared with respondents with a full diagnosis of cluster headache.

“Oxygen in particular had a high rate of complete effectiveness, a low rate of ineffectiveness, and a low rate of physical, medical, emotional, and psychological side effects,” the investigators said. “However, respondents reported that it was difficult to obtain.”

Limited insurance coverage of oxygen may affect access, even though the treatment has a Level A recommendation for the acute treatment of cluster headache in the American Headache Society guidelines, the authors said. Physicians also may pose a barrier. A prior study found that 12% of providers did not prescribe oxygen for cluster headache because they doubted its efficacy or did not know about it. In addition, there may be concerns that the treatment could be a fire hazard in a patient population that has high rates of smoking, the researchers said.

Limitations of the study include the survey’s use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of all triptans, rather than assessing individual triptan medications, such as sumatriptan subcutaneous, alone.

The study received funding from Autonomic Technologies and Clusterbusters. One of the authors has served as a paid consultant to Eli Lilly as a member of the data monitoring committee for clinical trials of galcanezumab for cluster headache and migraine.

This article was updated 3/7/2019.

[email protected]

SOURCE: Pearson SM et al. Headache. 2019 Jan 11. doi: 10.1111/head.13473.