Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.

Graça Victoria/Thinkstockphotos.com

The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.

During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.

In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.

The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.

The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.

They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.

The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.

“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.

The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.

Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.

According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”

Mental illness may contribute to mass violence, but the public presumption that all perpetrators have mental illness is inaccurate, and many have no diagnosed mental illness, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.

“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.

More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.

The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.

Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.

Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.

The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.

Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.

“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.

Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.

In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.

The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.

Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.

“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.

The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.

Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.

According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”

Mental illness may contribute to mass violence, but the public presumption that all perpetrators have mental illness is inaccurate, and many have no diagnosed mental illness, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.

“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.

More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.

The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.

Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.

Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.

The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.

Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.

“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.

Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.

In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.

The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.

Stigmatizing language in the public domain that falsely links U.S. gun violence to mental illness led the National Council for Behavioral Health to move up release of a report analyzing causes, impacts, and solutions of mass violence, according to Jack Rozel, MD.

“We were planning to release it in October but released it early to push back,” Dr. Rozel, a member of the report’s expert panel and medical director of resolve Crisis Services, said on the Aug. 21 MDedge Psychcast.

The 82-page report examines behavior-based motives and solutions related to mass violence in the United States (Parks J et al. National Council for Behavioral Health. 2019 Aug 6. “Mass Violence in America: Causes, Impacts and Solutions”). It was created by the Medical Director Institute, which advises the National Council on current issues affecting clinical practice.

Policy makers and the public often leap to conclusions about the role of mental illness in the actions of individuals responsible for mass violence, wrote the panel convened by the institute. The panel included not only clinicians such as Dr. Rozel with expertise in treating mental illness, but also researchers, educators, law enforcement personnel, FBI members, judges, policy makers, and parents.

According to the report’s executive summary, perpetrators of mass violence share certain traits independent of cultural, demographic, socioeconomic, and occupational factors. The most common perpetrators of mass violence are “males, often hopeless and harboring grievances that are frequently related to work, school, finances, or interpersonal relationships; feeling victimized and sympathizing with others whom they perceive to be similarly mistreated; indifference to life; and often subsequently dying by suicide.”

Mental illness may contribute to mass violence, but the public presumption that all perpetrators have mental illness is inaccurate, and many have no diagnosed mental illness, according to the report. In fact, many perpetrators do not suffer from any major psychiatric disorder, and most individuals who do suffer from mental illness are not violent.

“Lumping all mental illness together, and then assuming that acts that seem incomprehensible to the average person are due to mental illness, results in millions of harmless, nonviolent individuals recovering from treatable mental health conditions being subjected to stigma, rejection, discrimination and even unwarranted legal restrictions and social control,” the panel wrote. Recent episodes of mass violence in the United States can contribute to a generalized fear of individuals with mental illness, they added.

More research and strategies are needed to explore and address the root causes that contribute to acts of mass violence, including social problems and insufficient mental health care, the report said.

The panelists also offered recommendations for stakeholders, including health care organizations, schools, law enforcement, and community groups.

Recommendations for health care organizations in particular include establishing multidisciplinary teams for threat assessment and management that include not only security personnel, but also human resources, legal, and law enforcement. In addition, the panel recommended that health care staff be trained in lethal means reduction. “This is a rational strategy for lethal violence reduction and very helpful in combating suicide,” they said. However, staff also should be prepared for compassion fatigue and vicarious trauma, and health care organizations should develop resources for self-care and staff support.

Other recommendations include enacting state red flag laws that would remove guns from high-risk individuals for the short term, and reassessing the value of school safety protocols, such as bulletproof glass, zero tolerance policies, and active shooter drills.

The panel also offered recommendations for additional research on mass violence, including studies on “the nature and factors that contribute to mass violence, including neurobiological, psychological and sociological factors,” as well as research on methods of intervention and prevention of mass violence and the creation of a standardized analysis for mass violence incidence led by the Department of Justice with a multidisciplinary team.

Working with the media is important for engaging and educating the public about mental illness and mass violence, the panel members wrote. They recommended that all stakeholders in mental health develop messages in advance and protocols about how to respond to media requests for information about behavioral health.

“Talk about the role of treatment in helping people at risk of violence. Highlight the fact that most people with mental illnesses will never become violent. Speak to untreated or undertreated mental illness in combination with other risk factors,” they said.

Finally, they emphasized the need to remind the public to be aware of risk factors for mass violence, and the value of the “see something, say something” message.

In the Psychcast interview, Dr. Rozel said he and several colleagues will be conducting talks and training on these issues over the next few months, including at the Institute on Psychiatric Services conference (IPS 2019) in October in New York; at the National Council’s preconference (NatCon20) in April in Austin, Tex.; and at the American College of Emergency Physicians (ACEP 2019) meeting in October in Denver.

The National Council’s expert panel was led by Joe Parks, MD, medical director of the National Council; Donald W. Bechtold, MD, of the Colorado-based Jefferson Center for Mental Health; Sara Coffey, DO, of Oklahoma State University, Tulsa; Jeffrey A. Lieberman, MD, of Columbia University, New York; and Frank Shelp, MD, MPH, of Envolve Health, Atlanta.

Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.

Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden

Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.

For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.

The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.

Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.

The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.

Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.

Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.

Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden

Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.

For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.

The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.

Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.

The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.

Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.

Type 2 diabetes is a risk factor for heart failure and a common comorbidity in heart failure patients. New results from a large cohort study in Asia show that, for people with heart failure, having diabetes is associated with changes to the structure of the heart, lower quality of life, more readmissions to hospital, and higher risk of death.

Jonathan Yap, MBBS, MPH, of the National Heart Centre in Singapore, and colleagues, looked at data from a cohort enrolling 6,167 heart failure patients in 11 Asian countries for the prospective ASIAN-HF (Asian Sudden

Cardiac Death in Heart Failure) registry. The researchers identified 5,028 patients with heart failure and reduced left ventricle ejection fraction (LVEF; 22% women), of whom 40% had type 2 diabetes. They also looked at 1,139 patients in the registry with heart failure and preserved LVEF (51% women), of whom 45% had type 2 disease. Controls without heart failure (n = 985; 9% with diabetes) from the SHOP (Singapore Heart Failure Outcomes and Phenotypes) study were included in the analysis, which was published August 21 in the Journal of the American Heart Association.

For both heart failure phenotypes, diabetes was associated with left ventricular hypertrophy, but there was no similar association in patients without diabetes. Dr. Yap and his colleagues reported differences in cardiac remodeling based on heart failure phenotype: The reduced LVEF patients had more eccentric hypertrophy, or dilation, of the left ventricular chamber, whereas the preserved LVEF patients had more concentric hypertrophy, or thickening, of the left ventricular wall.

The researchers also reported that patients with diabetes had lower health-related quality of life scores in both heart failure groups, compared with patients without diabetes, although those in the latter group with preserved LVEF did significantly worse on some quality of life measures. Patients with diabetes had more heart failure rehospitalizations (adjusted hazard ratio, 1.27; 95% confidence interval, 1.05-1.54; P = .014) and higher 1-year rates of a combined measure of all-cause mortality and hospitalization for heart failure (aHR, 1.22; 95% CI, 1.05-1.41; P = .011). No differences were seen between phenotypes for these outcomes.

Dr. Yap and colleagues noted that this was the first large, multinational study investigating diabetes and heart failure in Asia and that “no prior studies have concomitantly included both HF types or controls without HF from the same population.” They listed among the study’s limitations a lack of uniform screening for diabetes that may have resulted in under-identification of diabetics in the cohort.

The Singapore government, the Biomedical Research Council, Boston Scientific, and Bayer sponsored the study. One coauthor disclosed receiving pharmaceutical industry support.

Source: Yap J et al. J Am Heart Assoc. 2019 Aug. doi: 10.1161/JAHA.119.013114.

The combination of decreasing hospital lengths of stay and increasing age and comorbidity of the United States population is a principal driver of the increased use of postacute care in the US.^1-3 Postacute care refers to care in long-term acute care hospitals, inpatient rehabilitation facilities, skilled nursing facilities (SNFs), and care provided by home health agencies after an acute hospitalization. In 2016, 43% of Medicare beneficiaries received postacute care after hospital discharge at the cost of $60 billion annually; nearly half of these received care in an SNF.⁴ Increasing recognition of the significant cost and poor outcomes of postacute care led to payment reforms, such as bundled payments, that incentivized less expensive forms of postacute care and improvements in outcomes.^5-9 Early evaluations suggested that hospitals are sensitive to these reforms and responded by significantly decreasing SNF utilization.^10,11 It remains unclear whether this was safe and effective.

In this context, increased attention to how hospital clinicians and hospitalized patients decide whether to use postacute care (and what form to use) is appropriate since the effect of payment reforms could negatively impact vulnerable populations of older adults without adequate protection.¹² Suboptimal decision-making can drive both overuse and inappropriate underuse of this expensive medical resource. Initial evidence suggests that patients and clinicians are poorly equipped to make high-quality decisions about postacute care, with significant deficits in both the decision-making process and content.^13-16 While these gaps are important to address, they may only be part of the problem. The fields of cognitive psychology and behavioral economics have revealed new insights into decision-making, demonstrating that people deviate from rational decision-making in predictable ways, termed decision heuristics, or cognitive biases.¹⁷ This growing field of research suggests heuristics or biases play important roles in decision-making and determining behavior, particularly in situations where there may be little information provided and the patient is stressed, tired, and ill—precisely like deciding on postacute care.¹⁸ However, it is currently unknown whether cognitive biases are at play when making hospital discharge decisions.

We sought to identify the most salient heuristics or cognitive biases patients may utilize when making decisions about postacute care at the end of their hospitalization and ways clinicians may contribute to these biases. The overall goal was to derive insights for improving postacute care decision-making.

Study Design

We conducted a secondary analysis on interviews with hospital and SNF clinicians as well as patients and their caregivers who were either leaving the hospital for an SNF or newly arrived in an SNF from the hospital to understand if cognitive biases were present and how they manifested themselves in a real-world clinical context.¹⁹ These interviews were part of a larger qualitative study that sought to understand how clinicians, patients, and their caregivers made decisions about postacute care, particularly related to SNFs.^13,14 This study represents the analysis of all our interviews, specifically examining decision-making bias. Participating sites, clinical roles, and both patient and caregiver characteristics (Table 1) in our cohort have been previously described.^13,14

Analysis

We used a team-based approach to framework analysis, which has been used in other decision-making studies¹⁴, including those measuring cognitive bias.²⁰ A limitation in cognitive bias research is the lack of a standardized list or categorization of cognitive biases. We reviewed prior systematic^17,21 and narrative reviews^18,22, as well as prior studies describing examples of cognitive biases playing a role in decision-making about therapy²⁰ to construct a list of possible cognitive biases to evaluate and narrow these a priori to potential biases relevant to the decision about postacute care based on our prior work (Table 2).

We applied this framework to analyze transcripts through an iterative process of deductive coding and reviewing across four reviewers (ML, RA, AL, CL) and a hospitalist physician with expertise leading qualitative studies (REB).

Intercoder consensus was built through team discussion by resolving points of disagreement.²³ Consistency of coding was regularly checked by having more than one investigator code individual manuscripts and comparing coding, and discrepancies were resolved through team discussion. We triangulated the data (shared our preliminary results) using a larger study team, including an expert in behavioral economics (SRG), physicians at study sites (EC, RA), and an anthropologist with expertise in qualitative methods (CL). We did this to ensure credibility (to what extent the findings are credible or believable) and confirmability of findings (ensuring the findings are based on participant narratives rather than researcher biases).

We reviewed a total of 105 interviews with 25 hospital clinicians, 20 SNF clinicians, 21 patients and 14 caregivers in the hospital, and 15 patients and 10 caregivers in the SNF setting (Table 1). We found authority bias/halo effect; default/status quo bias, anchoring bias, and framing was commonly present in decision-making about postacute care in a SNF, whereas there were few if any examples of ambiguity aversion, availability heuristic, confirmation bias, optimism bias, or false consensus effect (Table 2).

Authority Bias/Halo Effect

While most patients deferred to their inpatient teams when it came to decision-making, this effect seemed to differ across VA and non-VA settings. Veterans expressed a higher degree of potential authority bias regarding the VA as an institution, whereas older adults in non-VA settings saw physicians as the authority figure making decisions in their best interests.

Veterans expressed confidence in the VA regarding both whether to go to a SNF and where to go:

“The VA wouldn’t license [an SNF] if they didn’t have a good reputation for care, cleanliness, things of that nature” (Veteran, VA CLC)

“I just knew the VA would have my best interests at heart” (Veteran, VA CLC)

Their caregivers expressed similar confidence:

“I’m not gonna decide [on whether the patient they care for goes to postacute care], like I told you, that’s totally up to the VA. I have trust and faith in them…so wherever they send him, that’s where he’s going” (Caregiver, VA hospital)

In some cases, this perspective was closer to the halo effect: a positive experience with the care provider or the care team led the decision-makers to believe that their recommendations about postacute care would be similarly positive.

“I think we were very trusting in the sense that whatever happened the last time around, he survived it…they took care of him…he got back home, and he started his life again, you know, so why would we question what they’re telling us to do? (Caregiver, VA hospital)

In contrast to Veterans, non-Veteran patients seemed to experience authority bias when it came to the inpatient team.

“Well, I’d like to know more about the PTs [Physical Therapists] there, but I assume since they were recommended, they will be good.” (Patient, University hospital)

This perspective was especially apparent when it came to physicians:

“The level of trust that they [patients] put in their doctor is gonna outweigh what anyone else would say.” (Clinical liaison, SNF)

“[In response to a question about influences on the decision to go to rehab] I don’t…that’s not my decision to make, that’s the doctor’s decision.” (Patient, University hospital)

“They said so…[the doctor] said I needed to go to rehab, so I guess I do because it’s the doctor’s decision.” (Patient, University hospital)

Default/Status quo Bias

In a related way, patients and caregivers with exposure to a SNF seemed to default to the same SNF with which they had previous experience. This bias seems to be primarily related to knowing what to expect.

“He thinks it’s [a particular SNF] the right place for him now…he was there before and he knew, again, it was the right place for him to be” (Caregiver, VA hospital)

“It’s the only one I’ve ever been in…but they have a lot of activities; you have a lot of freedom, staff was good” (Patient, VA hospital)

“I’ve been [to this SNF] before and I kind of know what the program involves…so it was kind of like going home, not, going home is the wrong way to put it…I mean coming here is like something I know, you know, I didn’t need anybody to explain it to me.” (Patient, VA hospital)

“Anybody that’s been to [SNF], that would be their choice to go back to, and I guess I must’ve liked it that first time because I asked to go back again.” (Patient, University hospital)

Anchoring Bias

While anchoring bias was less frequent, it came up in two domains: first, related to costs of care, and second, related to facility characteristics. Costs came up most frequently for Veterans who preferred to move their care to the VA for cost reasons, which appeared in these cases to overshadow other considerations:

“I kept emphasizing that the VA could do all the same things at a lot more reasonable price. The whole purpose of having the VA is for the Veteran, so that…we can get the healthcare that we need at a more reasonable [sic] or a reasonable price.” (Veteran, CLC)

“I think the CLC [VA SNF] is going to take care of her probably the same way any other facility of its type would, unless she were in a private facility, but you know, that costs a lot more money.” (Caregiver, VA hospital)

Patients occasionally had striking responses to particular characteristics of SNFs, regardless of whether this was a central feature or related to their rehabilitation:

“The social worker comes and talks to me about the nursing home where cats are running around, you know, to infect my leg or spin their little cat hairs into my lungs and make my asthma worse…I’m going to have to beg the nurses or the aides or the family or somebody to clean the cat…” (Veteran, VA hospital)

Framing

Framing was the strongest theme among clinician interviews in our sample. Clinicians most frequently described the SNF as a place where patients could recover function (a positive frame), explaining risks (eg, rehospitalization) associated with alternative postacute care options besides the SNF in great detail.

“Aside from explaining the benefits of going and…having that 24-hour care, having the therapies provided to them [the patients], talking about them getting stronger, phrasing it in such a way that patients sometimes are more agreeable, like not calling it a skilled nursing facility, calling it a rehab you know, for them to get physically stronger so they can be the most independent that they can once they do go home, and also explaining … we think that this would be the best plan to prevent them from coming back to the hospital, so those are some of the things that we’ll mention to patients to try and educate them and get them to be agreeable for placement.” (Social worker, University hospital)

Clinicians avoided negative associations with “nursing home” (even though all SNFs are nursing homes) and tended to use more positive frames such as “rehabilitation facility.”

“Use the word rehab….we definitely use the word rehab, to get more therapy, to go home; it’s not a, we really emphasize it’s not a nursing home, it’s not to go to stay forever.” (Physical therapist, safety-net hospital)

Clinicians used a frame of “safety” when discussing the SNF and used a frame of “risk” when discussing alternative postacute care options such as returning home. We did not find examples of clinicians discussing similar risks in going to a SNF even for risks, such as falling, which exist in both settings.

“I’ve talked to them primarily on an avenue of safety because I think people want and they value independence, they value making sure they can get home, but you know, a lot of the times they understand safety is, it can be a concern and outlining that our goal is to make sure that they’re safe and they stay home, and I tend to broach the subject saying that our therapists believe that they might not be safe at home in the moment, but they have potential goals to be safe later on if we continue therapy. I really highlight safety being the major driver of our discussion.” (Physician, VA hospital)

In some cases, framing was so overt that other risk-mitigating options (eg, home healthcare) are not discussed.

“I definitely tend to explain the ideal first. I’m not going to bring up home care when we really think somebody should go to rehab, however, once people say I don’t want to do that, I’m not going, then that’s when I’m like OK, well, let’s talk to the doctors, but we can see about other supports in the home.” (Social worker, VA hospital)

In a large sample of patients and their caregivers, as well as multidisciplinary clinicians at three different hospitals and three SNFs, we found authority bias/halo effect and framing biases were most common and seemed most impactful. Default/status quo bias and anchoring bias were also present in decision-making about a SNF. The combination of authority bias/halo effect and framing biases could synergistically interact to augment the likelihood of patients accepting a SNF for postacute care. Patients who had been to a SNF before seemed more likely to choose the SNF they had experienced previously even if they had no other postacute care experiences, and could be highly influenced by isolated characteristics of that facility (such as the physical environment or cost of care).

It is important to mention that cognitive biases do not necessarily have a negative impact: indeed, as Kahneman and Tversky point out, these are useful heuristics from “fast” thinking that are often effective.²⁴ For example, clinicians may be trying to act in the best interests of the patient when framing the decision in terms of regaining function and averting loss of safety and independence. However, the evidence base regarding the outcomes of an SNF versus other postacute options is not robust, and this decision-making is complex. While this decision was most commonly framed in terms of rehabilitation and returning home, the fact that only about half of patients have returned to the community by 100 days⁴ was not discussed in any interview. In fact, initial evidence suggests replacing the SNF with home healthcare in patients with hip and knee arthroplasty may reduce costs without worsening clinical outcomes.⁶ However, across a broader population, SNFs significantly reduce 30-day readmissions when directly compared with home healthcare, but other clinical outcomes are similar.²⁵ This evidence suggests that the “right” postacute care option for an individual patient is not clear, highlighting a key role biases may play in decision-making. Further, the nebulous concept of “safety” could introduce potential disparities related to social determinants of health.¹² The observed inclination to accept an SNF with which the individual had prior experience may be influenced by the acceptability of this choice because of personal factors or prior research, even if it also represents a bias by limiting the consideration of current alternatives.

Our findings complement those of others in the literature which have also identified profound gaps in discharge decision-making among patients and clinicians,^13-16,26-31 though to our knowledge the role of cognitive biases in these decisions has not been explored. This study also addresses gaps in the cognitive bias literature, including the need for real-world data rather than hypothetical vignettes,¹⁷ and evaluation of treatment and management decisions rather than diagnoses, which have been more commonly studied.²¹

These findings have implications for both individual clinicians and healthcare institutions. In the immediate term, these findings may serve as a call to discharging clinicians to modulate language and “debias” their conversations with patients about care after discharge.^18,22 Shared decision-making requires an informed choice by patients based on their goals and values; framing a decision in a way that puts the clinician’s goals or values (eg, safety) ahead of patient values (eg, independence and autonomy) or limits disclosure (eg, a “rehab” is a nursing home) in the hope of influencing choice may be more consistent with framing bias and less with shared decision-making.¹⁴ Although controversy exists about the best way to “debias” oneself,³² self-awareness of bias is increasingly recognized across healthcare venues as critical to improving care for vulnerable populations.³³ The use of data rather than vignettes may be a useful debiasing strategy, although the limitations of currently available data (eg, capturing nursing home quality) are increasingly recognized.³⁴ From a policy and health system perspective, cognitive biases should be integrated into the development of decision aids to facilitate informed, shared, and high-quality decision-making that incorporates patient values, and perhaps “nudges” from behavioral economics to assist patients in choosing the right postdischarge care for them. Such nudges use principles of framing to influence care without restricting choice.³⁵ As the science informing best practice regarding postacute care improves, identifying the “right” postdischarge care may become easier and recommendations more evidence-based.³⁶

Strengths of the study include a large, diverse sample of patients, caregivers, and clinicians in both the hospital and SNF setting. Also, we used a team-based analysis with an experienced team and a deep knowledge of the data, including triangulation with clinicians to verify results. However, all hospitals and SNFs were located in a single metropolitan area, and responses may vary by region or population density. All three hospitals have housestaff teaching programs, and at the time of the interviews all three community SNFs were “five-star” facilities on the Nursing Home Compare website; results may be different at community hospitals or other SNFs. Hospitalists were the only physician group sampled in the hospital as they provide the majority of inpatient care to older adults; geriatricians, in particular, may have had different perspectives. Since we intended to explore whether cognitive biases were present overall, we did not evaluate whether cognitive biases differed by role or subgroup (by clinician type, patient, or caregiver), but this may be a promising area to explore in future work. Many cognitive biases have been described, and there are likely additional biases we did not identify. To confirm the generalizability of these findings, they should be studied in a larger, more generalizable sample of respondents in future work.

Cognitive biases play an important role in patient decision-making about postacute care, particularly regarding SNF care. As postacute care undergoes a transformation spurred by payment reforms, it is more important than ever to ensure that patients understand their choices at hospital discharge and can make a high-quality decision consistent with their goals.

The combination of decreasing hospital lengths of stay and increasing age and comorbidity of the United States population is a principal driver of the increased use of postacute care in the US.^1-3 Postacute care refers to care in long-term acute care hospitals, inpatient rehabilitation facilities, skilled nursing facilities (SNFs), and care provided by home health agencies after an acute hospitalization. In 2016, 43% of Medicare beneficiaries received postacute care after hospital discharge at the cost of $60 billion annually; nearly half of these received care in an SNF.⁴ Increasing recognition of the significant cost and poor outcomes of postacute care led to payment reforms, such as bundled payments, that incentivized less expensive forms of postacute care and improvements in outcomes.^5-9 Early evaluations suggested that hospitals are sensitive to these reforms and responded by significantly decreasing SNF utilization.^10,11 It remains unclear whether this was safe and effective.

In this context, increased attention to how hospital clinicians and hospitalized patients decide whether to use postacute care (and what form to use) is appropriate since the effect of payment reforms could negatively impact vulnerable populations of older adults without adequate protection.¹² Suboptimal decision-making can drive both overuse and inappropriate underuse of this expensive medical resource. Initial evidence suggests that patients and clinicians are poorly equipped to make high-quality decisions about postacute care, with significant deficits in both the decision-making process and content.^13-16 While these gaps are important to address, they may only be part of the problem. The fields of cognitive psychology and behavioral economics have revealed new insights into decision-making, demonstrating that people deviate from rational decision-making in predictable ways, termed decision heuristics, or cognitive biases.¹⁷ This growing field of research suggests heuristics or biases play important roles in decision-making and determining behavior, particularly in situations where there may be little information provided and the patient is stressed, tired, and ill—precisely like deciding on postacute care.¹⁸ However, it is currently unknown whether cognitive biases are at play when making hospital discharge decisions.

We sought to identify the most salient heuristics or cognitive biases patients may utilize when making decisions about postacute care at the end of their hospitalization and ways clinicians may contribute to these biases. The overall goal was to derive insights for improving postacute care decision-making.

Study Design

We conducted a secondary analysis on interviews with hospital and SNF clinicians as well as patients and their caregivers who were either leaving the hospital for an SNF or newly arrived in an SNF from the hospital to understand if cognitive biases were present and how they manifested themselves in a real-world clinical context.¹⁹ These interviews were part of a larger qualitative study that sought to understand how clinicians, patients, and their caregivers made decisions about postacute care, particularly related to SNFs.^13,14 This study represents the analysis of all our interviews, specifically examining decision-making bias. Participating sites, clinical roles, and both patient and caregiver characteristics (Table 1) in our cohort have been previously described.^13,14

Analysis

We used a team-based approach to framework analysis, which has been used in other decision-making studies¹⁴, including those measuring cognitive bias.²⁰ A limitation in cognitive bias research is the lack of a standardized list or categorization of cognitive biases. We reviewed prior systematic^17,21 and narrative reviews^18,22, as well as prior studies describing examples of cognitive biases playing a role in decision-making about therapy²⁰ to construct a list of possible cognitive biases to evaluate and narrow these a priori to potential biases relevant to the decision about postacute care based on our prior work (Table 2).

We applied this framework to analyze transcripts through an iterative process of deductive coding and reviewing across four reviewers (ML, RA, AL, CL) and a hospitalist physician with expertise leading qualitative studies (REB).

Intercoder consensus was built through team discussion by resolving points of disagreement.²³ Consistency of coding was regularly checked by having more than one investigator code individual manuscripts and comparing coding, and discrepancies were resolved through team discussion. We triangulated the data (shared our preliminary results) using a larger study team, including an expert in behavioral economics (SRG), physicians at study sites (EC, RA), and an anthropologist with expertise in qualitative methods (CL). We did this to ensure credibility (to what extent the findings are credible or believable) and confirmability of findings (ensuring the findings are based on participant narratives rather than researcher biases).

We reviewed a total of 105 interviews with 25 hospital clinicians, 20 SNF clinicians, 21 patients and 14 caregivers in the hospital, and 15 patients and 10 caregivers in the SNF setting (Table 1). We found authority bias/halo effect; default/status quo bias, anchoring bias, and framing was commonly present in decision-making about postacute care in a SNF, whereas there were few if any examples of ambiguity aversion, availability heuristic, confirmation bias, optimism bias, or false consensus effect (Table 2).

Authority Bias/Halo Effect

While most patients deferred to their inpatient teams when it came to decision-making, this effect seemed to differ across VA and non-VA settings. Veterans expressed a higher degree of potential authority bias regarding the VA as an institution, whereas older adults in non-VA settings saw physicians as the authority figure making decisions in their best interests.

Veterans expressed confidence in the VA regarding both whether to go to a SNF and where to go:

“The VA wouldn’t license [an SNF] if they didn’t have a good reputation for care, cleanliness, things of that nature” (Veteran, VA CLC)

“I just knew the VA would have my best interests at heart” (Veteran, VA CLC)

Their caregivers expressed similar confidence:

“I’m not gonna decide [on whether the patient they care for goes to postacute care], like I told you, that’s totally up to the VA. I have trust and faith in them…so wherever they send him, that’s where he’s going” (Caregiver, VA hospital)

In some cases, this perspective was closer to the halo effect: a positive experience with the care provider or the care team led the decision-makers to believe that their recommendations about postacute care would be similarly positive.

“I think we were very trusting in the sense that whatever happened the last time around, he survived it…they took care of him…he got back home, and he started his life again, you know, so why would we question what they’re telling us to do? (Caregiver, VA hospital)

In contrast to Veterans, non-Veteran patients seemed to experience authority bias when it came to the inpatient team.

“Well, I’d like to know more about the PTs [Physical Therapists] there, but I assume since they were recommended, they will be good.” (Patient, University hospital)

This perspective was especially apparent when it came to physicians:

“The level of trust that they [patients] put in their doctor is gonna outweigh what anyone else would say.” (Clinical liaison, SNF)

“[In response to a question about influences on the decision to go to rehab] I don’t…that’s not my decision to make, that’s the doctor’s decision.” (Patient, University hospital)

“They said so…[the doctor] said I needed to go to rehab, so I guess I do because it’s the doctor’s decision.” (Patient, University hospital)

Default/Status quo Bias

In a related way, patients and caregivers with exposure to a SNF seemed to default to the same SNF with which they had previous experience. This bias seems to be primarily related to knowing what to expect.

“He thinks it’s [a particular SNF] the right place for him now…he was there before and he knew, again, it was the right place for him to be” (Caregiver, VA hospital)

“It’s the only one I’ve ever been in…but they have a lot of activities; you have a lot of freedom, staff was good” (Patient, VA hospital)

“I’ve been [to this SNF] before and I kind of know what the program involves…so it was kind of like going home, not, going home is the wrong way to put it…I mean coming here is like something I know, you know, I didn’t need anybody to explain it to me.” (Patient, VA hospital)

“Anybody that’s been to [SNF], that would be their choice to go back to, and I guess I must’ve liked it that first time because I asked to go back again.” (Patient, University hospital)

Anchoring Bias

While anchoring bias was less frequent, it came up in two domains: first, related to costs of care, and second, related to facility characteristics. Costs came up most frequently for Veterans who preferred to move their care to the VA for cost reasons, which appeared in these cases to overshadow other considerations:

“I kept emphasizing that the VA could do all the same things at a lot more reasonable price. The whole purpose of having the VA is for the Veteran, so that…we can get the healthcare that we need at a more reasonable [sic] or a reasonable price.” (Veteran, CLC)

“I think the CLC [VA SNF] is going to take care of her probably the same way any other facility of its type would, unless she were in a private facility, but you know, that costs a lot more money.” (Caregiver, VA hospital)

Patients occasionally had striking responses to particular characteristics of SNFs, regardless of whether this was a central feature or related to their rehabilitation:

“The social worker comes and talks to me about the nursing home where cats are running around, you know, to infect my leg or spin their little cat hairs into my lungs and make my asthma worse…I’m going to have to beg the nurses or the aides or the family or somebody to clean the cat…” (Veteran, VA hospital)

Framing

Framing was the strongest theme among clinician interviews in our sample. Clinicians most frequently described the SNF as a place where patients could recover function (a positive frame), explaining risks (eg, rehospitalization) associated with alternative postacute care options besides the SNF in great detail.

“Aside from explaining the benefits of going and…having that 24-hour care, having the therapies provided to them [the patients], talking about them getting stronger, phrasing it in such a way that patients sometimes are more agreeable, like not calling it a skilled nursing facility, calling it a rehab you know, for them to get physically stronger so they can be the most independent that they can once they do go home, and also explaining … we think that this would be the best plan to prevent them from coming back to the hospital, so those are some of the things that we’ll mention to patients to try and educate them and get them to be agreeable for placement.” (Social worker, University hospital)

Clinicians avoided negative associations with “nursing home” (even though all SNFs are nursing homes) and tended to use more positive frames such as “rehabilitation facility.”

“Use the word rehab….we definitely use the word rehab, to get more therapy, to go home; it’s not a, we really emphasize it’s not a nursing home, it’s not to go to stay forever.” (Physical therapist, safety-net hospital)

Clinicians used a frame of “safety” when discussing the SNF and used a frame of “risk” when discussing alternative postacute care options such as returning home. We did not find examples of clinicians discussing similar risks in going to a SNF even for risks, such as falling, which exist in both settings.

“I’ve talked to them primarily on an avenue of safety because I think people want and they value independence, they value making sure they can get home, but you know, a lot of the times they understand safety is, it can be a concern and outlining that our goal is to make sure that they’re safe and they stay home, and I tend to broach the subject saying that our therapists believe that they might not be safe at home in the moment, but they have potential goals to be safe later on if we continue therapy. I really highlight safety being the major driver of our discussion.” (Physician, VA hospital)

In some cases, framing was so overt that other risk-mitigating options (eg, home healthcare) are not discussed.

“I definitely tend to explain the ideal first. I’m not going to bring up home care when we really think somebody should go to rehab, however, once people say I don’t want to do that, I’m not going, then that’s when I’m like OK, well, let’s talk to the doctors, but we can see about other supports in the home.” (Social worker, VA hospital)

In a large sample of patients and their caregivers, as well as multidisciplinary clinicians at three different hospitals and three SNFs, we found authority bias/halo effect and framing biases were most common and seemed most impactful. Default/status quo bias and anchoring bias were also present in decision-making about a SNF. The combination of authority bias/halo effect and framing biases could synergistically interact to augment the likelihood of patients accepting a SNF for postacute care. Patients who had been to a SNF before seemed more likely to choose the SNF they had experienced previously even if they had no other postacute care experiences, and could be highly influenced by isolated characteristics of that facility (such as the physical environment or cost of care).

It is important to mention that cognitive biases do not necessarily have a negative impact: indeed, as Kahneman and Tversky point out, these are useful heuristics from “fast” thinking that are often effective.²⁴ For example, clinicians may be trying to act in the best interests of the patient when framing the decision in terms of regaining function and averting loss of safety and independence. However, the evidence base regarding the outcomes of an SNF versus other postacute options is not robust, and this decision-making is complex. While this decision was most commonly framed in terms of rehabilitation and returning home, the fact that only about half of patients have returned to the community by 100 days⁴ was not discussed in any interview. In fact, initial evidence suggests replacing the SNF with home healthcare in patients with hip and knee arthroplasty may reduce costs without worsening clinical outcomes.⁶ However, across a broader population, SNFs significantly reduce 30-day readmissions when directly compared with home healthcare, but other clinical outcomes are similar.²⁵ This evidence suggests that the “right” postacute care option for an individual patient is not clear, highlighting a key role biases may play in decision-making. Further, the nebulous concept of “safety” could introduce potential disparities related to social determinants of health.¹² The observed inclination to accept an SNF with which the individual had prior experience may be influenced by the acceptability of this choice because of personal factors or prior research, even if it also represents a bias by limiting the consideration of current alternatives.

Our findings complement those of others in the literature which have also identified profound gaps in discharge decision-making among patients and clinicians,^13-16,26-31 though to our knowledge the role of cognitive biases in these decisions has not been explored. This study also addresses gaps in the cognitive bias literature, including the need for real-world data rather than hypothetical vignettes,¹⁷ and evaluation of treatment and management decisions rather than diagnoses, which have been more commonly studied.²¹

These findings have implications for both individual clinicians and healthcare institutions. In the immediate term, these findings may serve as a call to discharging clinicians to modulate language and “debias” their conversations with patients about care after discharge.^18,22 Shared decision-making requires an informed choice by patients based on their goals and values; framing a decision in a way that puts the clinician’s goals or values (eg, safety) ahead of patient values (eg, independence and autonomy) or limits disclosure (eg, a “rehab” is a nursing home) in the hope of influencing choice may be more consistent with framing bias and less with shared decision-making.¹⁴ Although controversy exists about the best way to “debias” oneself,³² self-awareness of bias is increasingly recognized across healthcare venues as critical to improving care for vulnerable populations.³³ The use of data rather than vignettes may be a useful debiasing strategy, although the limitations of currently available data (eg, capturing nursing home quality) are increasingly recognized.³⁴ From a policy and health system perspective, cognitive biases should be integrated into the development of decision aids to facilitate informed, shared, and high-quality decision-making that incorporates patient values, and perhaps “nudges” from behavioral economics to assist patients in choosing the right postdischarge care for them. Such nudges use principles of framing to influence care without restricting choice.³⁵ As the science informing best practice regarding postacute care improves, identifying the “right” postdischarge care may become easier and recommendations more evidence-based.³⁶

Strengths of the study include a large, diverse sample of patients, caregivers, and clinicians in both the hospital and SNF setting. Also, we used a team-based analysis with an experienced team and a deep knowledge of the data, including triangulation with clinicians to verify results. However, all hospitals and SNFs were located in a single metropolitan area, and responses may vary by region or population density. All three hospitals have housestaff teaching programs, and at the time of the interviews all three community SNFs were “five-star” facilities on the Nursing Home Compare website; results may be different at community hospitals or other SNFs. Hospitalists were the only physician group sampled in the hospital as they provide the majority of inpatient care to older adults; geriatricians, in particular, may have had different perspectives. Since we intended to explore whether cognitive biases were present overall, we did not evaluate whether cognitive biases differed by role or subgroup (by clinician type, patient, or caregiver), but this may be a promising area to explore in future work. Many cognitive biases have been described, and there are likely additional biases we did not identify. To confirm the generalizability of these findings, they should be studied in a larger, more generalizable sample of respondents in future work.

Cognitive biases play an important role in patient decision-making about postacute care, particularly regarding SNF care. As postacute care undergoes a transformation spurred by payment reforms, it is more important than ever to ensure that patients understand their choices at hospital discharge and can make a high-quality decision consistent with their goals.

The combination of decreasing hospital lengths of stay and increasing age and comorbidity of the United States population is a principal driver of the increased use of postacute care in the US.^1-3 Postacute care refers to care in long-term acute care hospitals, inpatient rehabilitation facilities, skilled nursing facilities (SNFs), and care provided by home health agencies after an acute hospitalization. In 2016, 43% of Medicare beneficiaries received postacute care after hospital discharge at the cost of $60 billion annually; nearly half of these received care in an SNF.⁴ Increasing recognition of the significant cost and poor outcomes of postacute care led to payment reforms, such as bundled payments, that incentivized less expensive forms of postacute care and improvements in outcomes.^5-9 Early evaluations suggested that hospitals are sensitive to these reforms and responded by significantly decreasing SNF utilization.^10,11 It remains unclear whether this was safe and effective.

In this context, increased attention to how hospital clinicians and hospitalized patients decide whether to use postacute care (and what form to use) is appropriate since the effect of payment reforms could negatively impact vulnerable populations of older adults without adequate protection.¹² Suboptimal decision-making can drive both overuse and inappropriate underuse of this expensive medical resource. Initial evidence suggests that patients and clinicians are poorly equipped to make high-quality decisions about postacute care, with significant deficits in both the decision-making process and content.^13-16 While these gaps are important to address, they may only be part of the problem. The fields of cognitive psychology and behavioral economics have revealed new insights into decision-making, demonstrating that people deviate from rational decision-making in predictable ways, termed decision heuristics, or cognitive biases.¹⁷ This growing field of research suggests heuristics or biases play important roles in decision-making and determining behavior, particularly in situations where there may be little information provided and the patient is stressed, tired, and ill—precisely like deciding on postacute care.¹⁸ However, it is currently unknown whether cognitive biases are at play when making hospital discharge decisions.

We sought to identify the most salient heuristics or cognitive biases patients may utilize when making decisions about postacute care at the end of their hospitalization and ways clinicians may contribute to these biases. The overall goal was to derive insights for improving postacute care decision-making.

Study Design

We conducted a secondary analysis on interviews with hospital and SNF clinicians as well as patients and their caregivers who were either leaving the hospital for an SNF or newly arrived in an SNF from the hospital to understand if cognitive biases were present and how they manifested themselves in a real-world clinical context.¹⁹ These interviews were part of a larger qualitative study that sought to understand how clinicians, patients, and their caregivers made decisions about postacute care, particularly related to SNFs.^13,14 This study represents the analysis of all our interviews, specifically examining decision-making bias. Participating sites, clinical roles, and both patient and caregiver characteristics (Table 1) in our cohort have been previously described.^13,14

Analysis

We used a team-based approach to framework analysis, which has been used in other decision-making studies¹⁴, including those measuring cognitive bias.²⁰ A limitation in cognitive bias research is the lack of a standardized list or categorization of cognitive biases. We reviewed prior systematic^17,21 and narrative reviews^18,22, as well as prior studies describing examples of cognitive biases playing a role in decision-making about therapy²⁰ to construct a list of possible cognitive biases to evaluate and narrow these a priori to potential biases relevant to the decision about postacute care based on our prior work (Table 2).

We applied this framework to analyze transcripts through an iterative process of deductive coding and reviewing across four reviewers (ML, RA, AL, CL) and a hospitalist physician with expertise leading qualitative studies (REB).

Intercoder consensus was built through team discussion by resolving points of disagreement.²³ Consistency of coding was regularly checked by having more than one investigator code individual manuscripts and comparing coding, and discrepancies were resolved through team discussion. We triangulated the data (shared our preliminary results) using a larger study team, including an expert in behavioral economics (SRG), physicians at study sites (EC, RA), and an anthropologist with expertise in qualitative methods (CL). We did this to ensure credibility (to what extent the findings are credible or believable) and confirmability of findings (ensuring the findings are based on participant narratives rather than researcher biases).

We reviewed a total of 105 interviews with 25 hospital clinicians, 20 SNF clinicians, 21 patients and 14 caregivers in the hospital, and 15 patients and 10 caregivers in the SNF setting (Table 1). We found authority bias/halo effect; default/status quo bias, anchoring bias, and framing was commonly present in decision-making about postacute care in a SNF, whereas there were few if any examples of ambiguity aversion, availability heuristic, confirmation bias, optimism bias, or false consensus effect (Table 2).

Authority Bias/Halo Effect

While most patients deferred to their inpatient teams when it came to decision-making, this effect seemed to differ across VA and non-VA settings. Veterans expressed a higher degree of potential authority bias regarding the VA as an institution, whereas older adults in non-VA settings saw physicians as the authority figure making decisions in their best interests.

Veterans expressed confidence in the VA regarding both whether to go to a SNF and where to go:

“The VA wouldn’t license [an SNF] if they didn’t have a good reputation for care, cleanliness, things of that nature” (Veteran, VA CLC)

“I just knew the VA would have my best interests at heart” (Veteran, VA CLC)

Their caregivers expressed similar confidence:

“I’m not gonna decide [on whether the patient they care for goes to postacute care], like I told you, that’s totally up to the VA. I have trust and faith in them…so wherever they send him, that’s where he’s going” (Caregiver, VA hospital)

In some cases, this perspective was closer to the halo effect: a positive experience with the care provider or the care team led the decision-makers to believe that their recommendations about postacute care would be similarly positive.

“I think we were very trusting in the sense that whatever happened the last time around, he survived it…they took care of him…he got back home, and he started his life again, you know, so why would we question what they’re telling us to do? (Caregiver, VA hospital)

In contrast to Veterans, non-Veteran patients seemed to experience authority bias when it came to the inpatient team.

“Well, I’d like to know more about the PTs [Physical Therapists] there, but I assume since they were recommended, they will be good.” (Patient, University hospital)

This perspective was especially apparent when it came to physicians:

“The level of trust that they [patients] put in their doctor is gonna outweigh what anyone else would say.” (Clinical liaison, SNF)

“[In response to a question about influences on the decision to go to rehab] I don’t…that’s not my decision to make, that’s the doctor’s decision.” (Patient, University hospital)

“They said so…[the doctor] said I needed to go to rehab, so I guess I do because it’s the doctor’s decision.” (Patient, University hospital)

Default/Status quo Bias

In a related way, patients and caregivers with exposure to a SNF seemed to default to the same SNF with which they had previous experience. This bias seems to be primarily related to knowing what to expect.

“He thinks it’s [a particular SNF] the right place for him now…he was there before and he knew, again, it was the right place for him to be” (Caregiver, VA hospital)

“It’s the only one I’ve ever been in…but they have a lot of activities; you have a lot of freedom, staff was good” (Patient, VA hospital)

“I’ve been [to this SNF] before and I kind of know what the program involves…so it was kind of like going home, not, going home is the wrong way to put it…I mean coming here is like something I know, you know, I didn’t need anybody to explain it to me.” (Patient, VA hospital)

“Anybody that’s been to [SNF], that would be their choice to go back to, and I guess I must’ve liked it that first time because I asked to go back again.” (Patient, University hospital)

Anchoring Bias

While anchoring bias was less frequent, it came up in two domains: first, related to costs of care, and second, related to facility characteristics. Costs came up most frequently for Veterans who preferred to move their care to the VA for cost reasons, which appeared in these cases to overshadow other considerations:

“I kept emphasizing that the VA could do all the same things at a lot more reasonable price. The whole purpose of having the VA is for the Veteran, so that…we can get the healthcare that we need at a more reasonable [sic] or a reasonable price.” (Veteran, CLC)

“I think the CLC [VA SNF] is going to take care of her probably the same way any other facility of its type would, unless she were in a private facility, but you know, that costs a lot more money.” (Caregiver, VA hospital)

Patients occasionally had striking responses to particular characteristics of SNFs, regardless of whether this was a central feature or related to their rehabilitation:

“The social worker comes and talks to me about the nursing home where cats are running around, you know, to infect my leg or spin their little cat hairs into my lungs and make my asthma worse…I’m going to have to beg the nurses or the aides or the family or somebody to clean the cat…” (Veteran, VA hospital)

Framing

Framing was the strongest theme among clinician interviews in our sample. Clinicians most frequently described the SNF as a place where patients could recover function (a positive frame), explaining risks (eg, rehospitalization) associated with alternative postacute care options besides the SNF in great detail.

“Aside from explaining the benefits of going and…having that 24-hour care, having the therapies provided to them [the patients], talking about them getting stronger, phrasing it in such a way that patients sometimes are more agreeable, like not calling it a skilled nursing facility, calling it a rehab you know, for them to get physically stronger so they can be the most independent that they can once they do go home, and also explaining … we think that this would be the best plan to prevent them from coming back to the hospital, so those are some of the things that we’ll mention to patients to try and educate them and get them to be agreeable for placement.” (Social worker, University hospital)

Clinicians avoided negative associations with “nursing home” (even though all SNFs are nursing homes) and tended to use more positive frames such as “rehabilitation facility.”

“Use the word rehab….we definitely use the word rehab, to get more therapy, to go home; it’s not a, we really emphasize it’s not a nursing home, it’s not to go to stay forever.” (Physical therapist, safety-net hospital)

Clinicians used a frame of “safety” when discussing the SNF and used a frame of “risk” when discussing alternative postacute care options such as returning home. We did not find examples of clinicians discussing similar risks in going to a SNF even for risks, such as falling, which exist in both settings.

“I’ve talked to them primarily on an avenue of safety because I think people want and they value independence, they value making sure they can get home, but you know, a lot of the times they understand safety is, it can be a concern and outlining that our goal is to make sure that they’re safe and they stay home, and I tend to broach the subject saying that our therapists believe that they might not be safe at home in the moment, but they have potential goals to be safe later on if we continue therapy. I really highlight safety being the major driver of our discussion.” (Physician, VA hospital)

In some cases, framing was so overt that other risk-mitigating options (eg, home healthcare) are not discussed.

“I definitely tend to explain the ideal first. I’m not going to bring up home care when we really think somebody should go to rehab, however, once people say I don’t want to do that, I’m not going, then that’s when I’m like OK, well, let’s talk to the doctors, but we can see about other supports in the home.” (Social worker, VA hospital)

In a large sample of patients and their caregivers, as well as multidisciplinary clinicians at three different hospitals and three SNFs, we found authority bias/halo effect and framing biases were most common and seemed most impactful. Default/status quo bias and anchoring bias were also present in decision-making about a SNF. The combination of authority bias/halo effect and framing biases could synergistically interact to augment the likelihood of patients accepting a SNF for postacute care. Patients who had been to a SNF before seemed more likely to choose the SNF they had experienced previously even if they had no other postacute care experiences, and could be highly influenced by isolated characteristics of that facility (such as the physical environment or cost of care).

It is important to mention that cognitive biases do not necessarily have a negative impact: indeed, as Kahneman and Tversky point out, these are useful heuristics from “fast” thinking that are often effective.²⁴ For example, clinicians may be trying to act in the best interests of the patient when framing the decision in terms of regaining function and averting loss of safety and independence. However, the evidence base regarding the outcomes of an SNF versus other postacute options is not robust, and this decision-making is complex. While this decision was most commonly framed in terms of rehabilitation and returning home, the fact that only about half of patients have returned to the community by 100 days⁴ was not discussed in any interview. In fact, initial evidence suggests replacing the SNF with home healthcare in patients with hip and knee arthroplasty may reduce costs without worsening clinical outcomes.⁶ However, across a broader population, SNFs significantly reduce 30-day readmissions when directly compared with home healthcare, but other clinical outcomes are similar.²⁵ This evidence suggests that the “right” postacute care option for an individual patient is not clear, highlighting a key role biases may play in decision-making. Further, the nebulous concept of “safety” could introduce potential disparities related to social determinants of health.¹² The observed inclination to accept an SNF with which the individual had prior experience may be influenced by the acceptability of this choice because of personal factors or prior research, even if it also represents a bias by limiting the consideration of current alternatives.

Our findings complement those of others in the literature which have also identified profound gaps in discharge decision-making among patients and clinicians,^13-16,26-31 though to our knowledge the role of cognitive biases in these decisions has not been explored. This study also addresses gaps in the cognitive bias literature, including the need for real-world data rather than hypothetical vignettes,¹⁷ and evaluation of treatment and management decisions rather than diagnoses, which have been more commonly studied.²¹

These findings have implications for both individual clinicians and healthcare institutions. In the immediate term, these findings may serve as a call to discharging clinicians to modulate language and “debias” their conversations with patients about care after discharge.^18,22 Shared decision-making requires an informed choice by patients based on their goals and values; framing a decision in a way that puts the clinician’s goals or values (eg, safety) ahead of patient values (eg, independence and autonomy) or limits disclosure (eg, a “rehab” is a nursing home) in the hope of influencing choice may be more consistent with framing bias and less with shared decision-making.¹⁴ Although controversy exists about the best way to “debias” oneself,³² self-awareness of bias is increasingly recognized across healthcare venues as critical to improving care for vulnerable populations.³³ The use of data rather than vignettes may be a useful debiasing strategy, although the limitations of currently available data (eg, capturing nursing home quality) are increasingly recognized.³⁴ From a policy and health system perspective, cognitive biases should be integrated into the development of decision aids to facilitate informed, shared, and high-quality decision-making that incorporates patient values, and perhaps “nudges” from behavioral economics to assist patients in choosing the right postdischarge care for them. Such nudges use principles of framing to influence care without restricting choice.³⁵ As the science informing best practice regarding postacute care improves, identifying the “right” postdischarge care may become easier and recommendations more evidence-based.³⁶

Strengths of the study include a large, diverse sample of patients, caregivers, and clinicians in both the hospital and SNF setting. Also, we used a team-based analysis with an experienced team and a deep knowledge of the data, including triangulation with clinicians to verify results. However, all hospitals and SNFs were located in a single metropolitan area, and responses may vary by region or population density. All three hospitals have housestaff teaching programs, and at the time of the interviews all three community SNFs were “five-star” facilities on the Nursing Home Compare website; results may be different at community hospitals or other SNFs. Hospitalists were the only physician group sampled in the hospital as they provide the majority of inpatient care to older adults; geriatricians, in particular, may have had different perspectives. Since we intended to explore whether cognitive biases were present overall, we did not evaluate whether cognitive biases differed by role or subgroup (by clinician type, patient, or caregiver), but this may be a promising area to explore in future work. Many cognitive biases have been described, and there are likely additional biases we did not identify. To confirm the generalizability of these findings, they should be studied in a larger, more generalizable sample of respondents in future work.

Cognitive biases play an important role in patient decision-making about postacute care, particularly regarding SNF care. As postacute care undergoes a transformation spurred by payment reforms, it is more important than ever to ensure that patients understand their choices at hospital discharge and can make a high-quality decision consistent with their goals.

Pediatric acute pancreatitis is being diagnosed more commonly, affecting approximately one per 10,000 children annually with an estimated inpatient cost burden of $200 million per year.^1,2 Common causes of pediatric acute pancreatitis include systemic illness, biliary disease, trauma, and medications; 13%-34% of cases are idiopathic.¹ Currently, substantial variation exists in the clinical management of this condition.^3,4 Hospitalists should familiarize themselves with the current literature, including the recent practice guideline by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).²

(Evidence quality: not graded, recommendation by expert consensus)

Recommendation 1. Diagnosis of acute pancreatitis in pediatric patients requires at least two of the following symptoms: abdominal pain compatible with acute pancreatitis, serum amylase and/or lipase values >3 times the upper limits of normal, and imaging findings consistent with acute pancreatitis.The most common symptoms of acute pancreatitis in children are epigastric or diffuse abdominal pain, vomiting, and irritability. Presentation varies by age, and diagnosis requires a high index of suspicion. Significant elevations in amylase and lipase levels are typically detected early in the disease course. The guideline does not specify a preferred serum biomarker in the diagnosis of pancreatitis but notes that lipase is more sensitive and specific than amylase, rises within 6 hours of symptoms, and stays elevated longer. Amylase levels rise faster but often normalize by 24 hours of symptom onset. Amylase and lipase can originate from extrapancreatic sources and may be elevated during acute illness in the absence of pancreatitis.

Laboratory testing to investigate the etiology of acute pancreatitis should include hepatic enzymes, bilirubin, triglyceride, and calcium levels. Although not typically necessary for diagnosis, imaging may demonstrate pancreatic edema or peripancreatic fluid, confirm disease complications, and identify obstructive causes. Transabdominal ultrasonography is indicated if biliary pancreatitis is suspected. Contrast-enhanced computed tomography should be considered for patients with severe presentation or deteriorating condition. Magnetic resonance cholangiopancreatography is useful in detecting pancreaticobiliary abnormalities.

Recommendation 2. Children with acute pancreatitis should be initially resuscitated with crystalloids, either with lactated Ringer’s or normal saline in the acute setting. These children should be provided 1.5-2 times maintenance intravenous fluids with monitoring of urine output over the next 24-48 hours.

Fluid resuscitation and maintenance are the current mainstays of therapy for pancreatitis. Prompt fluid administration corrects hypovolemia and may prevent potential complications. Early, aggressive fluid replacement in adults reduces the incidence of systemic inflammatory response syndrome and organ failure. Limited pediatric studies support correction of hypovolemia and/or circulatory compromise using 10-20 ml/kg boluses of isotonic crystalloid fluid. Although the literature is sparse regarding the rate of continued fluid replacement, the committee recommends patients receive 1.5-2 times maintenance intravenous fluid (IVF) with normal saline plus 5% dextrose for the first 24-48 hours. The rate of IVF administration should be adjusted based on volume status and urine output. IVF should be discontinued once the patient is able to maintain adequate hydration enterally. Cardiac, renal, and pulmonary complications of pancreatitis often present within the first 48 hours of illness and should prompt close monitoring with assessment of vital signs every four hours. The committee recommends monitoring serum electrolytes and renal function in the first 48 hours but does not offer guidance regarding the frequency of laboratory testing or the value of trending serum biomarkers.

Recommendation 3. Except in the presence of direct contraindications to use the gut, children with mild acute pancreatitis may benefit from early (within 48-72 hours of presentation) oral and enteral nutrition to decrease the length of stay (LOS) and the risk of organ dysfunction.

Adult studies suggest early enteral nutrition decreases complications and reduces LOS. Initiating enteral nutrition within 48 hours in children may have similar benefits. Several small pediatric studies have demonstrated a reduced LOS with early enteral feeds without an increase in complications. In a retrospective single-center study, children who were fed within the first 48 hours and received 1.5-2 times maintenance IVF had shorter LOS, less frequent intensive care admissions, and reduced severity of illness compared with those who were kept nil per os for the first 48 hours.⁵ Nasogastric or nasojejunal feeds may be initiated if a patient is unable to tolerate oral feeding. Parenteral nutrition should be reserved for children in whom enteral nutrition cannot be initiated within five to seven days.

Recommendation 4. Intravenous morphine or other opioids should be used for acute pancreatitis pain not responding to acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs).

Abdominal pain is the most common presenting symptom of pancreatitis, and pain control is an essential component of supportive care. There are no randomized trials identifying an optimal pain management regimen. The committee recommends the use of opioids for pain not controlled with acetaminophen and NSAIDs. Refractory pain may necessitate consultation with an acute pain specialist.

Recommendation 5. Routine use of prophylactic antibiotics, protease inhibitors, antioxidants, and probiotics is not recommended in acute pancreatitis.

Adult literature does not support routine use of antibiotics in acute pancreatitis, but their use may be beneficial in severe or recalcitrant cases. Pediatric literature neither confirms nor refutes this finding. The guideline does not recommend the use of antibiotics without signs of infection. Limited adult studies have shown protease inhibitors, antioxidants, and probiotics to be beneficial; however, no pediatric data support their use.

This guideline also discusses interventional and surgical procedures. Of note, biliary tract disease may necessitate endoscopic retrograde cholangiopancreatography or cholecystectomy. Such procedures should be considered in conjunction with subspecialty input.²

Methods in Preparing Guideline

The guideline development committee, funded by the NASPGHAN and the National Institutes of Diabetes and Digestive and Kidney Diseases, was composed of members of the NASPGHAN Pancreas Committee and included gastroenterologists from multiple sites.² Topics were selected via group discussion, and Medline searches included both adult and pediatric literature. Preliminary recommendations were presented at the 2016 World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Following revision, the 24 authors voted on each recommendation using a five-point Likert scale. A recommendation passed if 75% of the participants either agreed or strongly agreed with it. The authors reported no conflicts of interest.

Although the literature review was comprehensive, it lacked prospective pediatric studies and many of the recommendations were derived from adult research. The committee originally intended to grade the quality of evidence; however, the pediatric specific literature was underpowered and retrospective. Therefore, the committee opted to use consensus voting. The authors note that had the group used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, it would have returned grades of “low” or “very low” quality evidence.² The Hungarian Pancreatic Study Group and the European Pancreatic Club published a consensus guideline on the management of pediatric acute pancreatitis shortly after the NASPGHAN guideline, which offers similar conclusions.^2,6 The strength and generalizability of the NASPGHAN guideline are limited by its overreliance on adult literature, expert consensus, and small, retrospective pediatric studies to guide care.

This guideline highlights the need for pediatric research to guide the management of acute pancreatitis. The etiologies of pancreatitis in children are distinct from adults, where alcohol abuse and biliary disease are significant contributors.¹ Furthermore, age and environmental factors influence the presentation and clinical course.¹ Robust, prospective studies are needed to better understand the treatment outcomes of pediatric pancreatitis. Areas of further research include pediatric pancreatic severity scoring, ideal fluid composition and administration rate, enteral feed timing, optimal pain control, laboratory monitoring frequency, and adjuvant therapies.

Disclosures

Dr. Wall has nothing to disclose.

Pediatric acute pancreatitis is being diagnosed more commonly, affecting approximately one per 10,000 children annually with an estimated inpatient cost burden of $200 million per year.^1,2 Common causes of pediatric acute pancreatitis include systemic illness, biliary disease, trauma, and medications; 13%-34% of cases are idiopathic.¹ Currently, substantial variation exists in the clinical management of this condition.^3,4 Hospitalists should familiarize themselves with the current literature, including the recent practice guideline by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).²

(Evidence quality: not graded, recommendation by expert consensus)

Recommendation 1. Diagnosis of acute pancreatitis in pediatric patients requires at least two of the following symptoms: abdominal pain compatible with acute pancreatitis, serum amylase and/or lipase values >3 times the upper limits of normal, and imaging findings consistent with acute pancreatitis.The most common symptoms of acute pancreatitis in children are epigastric or diffuse abdominal pain, vomiting, and irritability. Presentation varies by age, and diagnosis requires a high index of suspicion. Significant elevations in amylase and lipase levels are typically detected early in the disease course. The guideline does not specify a preferred serum biomarker in the diagnosis of pancreatitis but notes that lipase is more sensitive and specific than amylase, rises within 6 hours of symptoms, and stays elevated longer. Amylase levels rise faster but often normalize by 24 hours of symptom onset. Amylase and lipase can originate from extrapancreatic sources and may be elevated during acute illness in the absence of pancreatitis.

Laboratory testing to investigate the etiology of acute pancreatitis should include hepatic enzymes, bilirubin, triglyceride, and calcium levels. Although not typically necessary for diagnosis, imaging may demonstrate pancreatic edema or peripancreatic fluid, confirm disease complications, and identify obstructive causes. Transabdominal ultrasonography is indicated if biliary pancreatitis is suspected. Contrast-enhanced computed tomography should be considered for patients with severe presentation or deteriorating condition. Magnetic resonance cholangiopancreatography is useful in detecting pancreaticobiliary abnormalities.

Recommendation 2. Children with acute pancreatitis should be initially resuscitated with crystalloids, either with lactated Ringer’s or normal saline in the acute setting. These children should be provided 1.5-2 times maintenance intravenous fluids with monitoring of urine output over the next 24-48 hours.

Fluid resuscitation and maintenance are the current mainstays of therapy for pancreatitis. Prompt fluid administration corrects hypovolemia and may prevent potential complications. Early, aggressive fluid replacement in adults reduces the incidence of systemic inflammatory response syndrome and organ failure. Limited pediatric studies support correction of hypovolemia and/or circulatory compromise using 10-20 ml/kg boluses of isotonic crystalloid fluid. Although the literature is sparse regarding the rate of continued fluid replacement, the committee recommends patients receive 1.5-2 times maintenance intravenous fluid (IVF) with normal saline plus 5% dextrose for the first 24-48 hours. The rate of IVF administration should be adjusted based on volume status and urine output. IVF should be discontinued once the patient is able to maintain adequate hydration enterally. Cardiac, renal, and pulmonary complications of pancreatitis often present within the first 48 hours of illness and should prompt close monitoring with assessment of vital signs every four hours. The committee recommends monitoring serum electrolytes and renal function in the first 48 hours but does not offer guidance regarding the frequency of laboratory testing or the value of trending serum biomarkers.

Recommendation 3. Except in the presence of direct contraindications to use the gut, children with mild acute pancreatitis may benefit from early (within 48-72 hours of presentation) oral and enteral nutrition to decrease the length of stay (LOS) and the risk of organ dysfunction.

Adult studies suggest early enteral nutrition decreases complications and reduces LOS. Initiating enteral nutrition within 48 hours in children may have similar benefits. Several small pediatric studies have demonstrated a reduced LOS with early enteral feeds without an increase in complications. In a retrospective single-center study, children who were fed within the first 48 hours and received 1.5-2 times maintenance IVF had shorter LOS, less frequent intensive care admissions, and reduced severity of illness compared with those who were kept nil per os for the first 48 hours.⁵ Nasogastric or nasojejunal feeds may be initiated if a patient is unable to tolerate oral feeding. Parenteral nutrition should be reserved for children in whom enteral nutrition cannot be initiated within five to seven days.

Recommendation 4. Intravenous morphine or other opioids should be used for acute pancreatitis pain not responding to acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs).

Abdominal pain is the most common presenting symptom of pancreatitis, and pain control is an essential component of supportive care. There are no randomized trials identifying an optimal pain management regimen. The committee recommends the use of opioids for pain not controlled with acetaminophen and NSAIDs. Refractory pain may necessitate consultation with an acute pain specialist.

Recommendation 5. Routine use of prophylactic antibiotics, protease inhibitors, antioxidants, and probiotics is not recommended in acute pancreatitis.

Adult literature does not support routine use of antibiotics in acute pancreatitis, but their use may be beneficial in severe or recalcitrant cases. Pediatric literature neither confirms nor refutes this finding. The guideline does not recommend the use of antibiotics without signs of infection. Limited adult studies have shown protease inhibitors, antioxidants, and probiotics to be beneficial; however, no pediatric data support their use.

This guideline also discusses interventional and surgical procedures. Of note, biliary tract disease may necessitate endoscopic retrograde cholangiopancreatography or cholecystectomy. Such procedures should be considered in conjunction with subspecialty input.²

Methods in Preparing Guideline

The guideline development committee, funded by the NASPGHAN and the National Institutes of Diabetes and Digestive and Kidney Diseases, was composed of members of the NASPGHAN Pancreas Committee and included gastroenterologists from multiple sites.² Topics were selected via group discussion, and Medline searches included both adult and pediatric literature. Preliminary recommendations were presented at the 2016 World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Following revision, the 24 authors voted on each recommendation using a five-point Likert scale. A recommendation passed if 75% of the participants either agreed or strongly agreed with it. The authors reported no conflicts of interest.

Although the literature review was comprehensive, it lacked prospective pediatric studies and many of the recommendations were derived from adult research. The committee originally intended to grade the quality of evidence; however, the pediatric specific literature was underpowered and retrospective. Therefore, the committee opted to use consensus voting. The authors note that had the group used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, it would have returned grades of “low” or “very low” quality evidence.² The Hungarian Pancreatic Study Group and the European Pancreatic Club published a consensus guideline on the management of pediatric acute pancreatitis shortly after the NASPGHAN guideline, which offers similar conclusions.^2,6 The strength and generalizability of the NASPGHAN guideline are limited by its overreliance on adult literature, expert consensus, and small, retrospective pediatric studies to guide care.

This guideline highlights the need for pediatric research to guide the management of acute pancreatitis. The etiologies of pancreatitis in children are distinct from adults, where alcohol abuse and biliary disease are significant contributors.¹ Furthermore, age and environmental factors influence the presentation and clinical course.¹ Robust, prospective studies are needed to better understand the treatment outcomes of pediatric pancreatitis. Areas of further research include pediatric pancreatic severity scoring, ideal fluid composition and administration rate, enteral feed timing, optimal pain control, laboratory monitoring frequency, and adjuvant therapies.

Disclosures

Dr. Wall has nothing to disclose.

Pediatric acute pancreatitis is being diagnosed more commonly, affecting approximately one per 10,000 children annually with an estimated inpatient cost burden of $200 million per year.^1,2 Common causes of pediatric acute pancreatitis include systemic illness, biliary disease, trauma, and medications; 13%-34% of cases are idiopathic.¹ Currently, substantial variation exists in the clinical management of this condition.^3,4 Hospitalists should familiarize themselves with the current literature, including the recent practice guideline by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).²

(Evidence quality: not graded, recommendation by expert consensus)

Recommendation 1. Diagnosis of acute pancreatitis in pediatric patients requires at least two of the following symptoms: abdominal pain compatible with acute pancreatitis, serum amylase and/or lipase values >3 times the upper limits of normal, and imaging findings consistent with acute pancreatitis.The most common symptoms of acute pancreatitis in children are epigastric or diffuse abdominal pain, vomiting, and irritability. Presentation varies by age, and diagnosis requires a high index of suspicion. Significant elevations in amylase and lipase levels are typically detected early in the disease course. The guideline does not specify a preferred serum biomarker in the diagnosis of pancreatitis but notes that lipase is more sensitive and specific than amylase, rises within 6 hours of symptoms, and stays elevated longer. Amylase levels rise faster but often normalize by 24 hours of symptom onset. Amylase and lipase can originate from extrapancreatic sources and may be elevated during acute illness in the absence of pancreatitis.

Laboratory testing to investigate the etiology of acute pancreatitis should include hepatic enzymes, bilirubin, triglyceride, and calcium levels. Although not typically necessary for diagnosis, imaging may demonstrate pancreatic edema or peripancreatic fluid, confirm disease complications, and identify obstructive causes. Transabdominal ultrasonography is indicated if biliary pancreatitis is suspected. Contrast-enhanced computed tomography should be considered for patients with severe presentation or deteriorating condition. Magnetic resonance cholangiopancreatography is useful in detecting pancreaticobiliary abnormalities.

Recommendation 2. Children with acute pancreatitis should be initially resuscitated with crystalloids, either with lactated Ringer’s or normal saline in the acute setting. These children should be provided 1.5-2 times maintenance intravenous fluids with monitoring of urine output over the next 24-48 hours.

Fluid resuscitation and maintenance are the current mainstays of therapy for pancreatitis. Prompt fluid administration corrects hypovolemia and may prevent potential complications. Early, aggressive fluid replacement in adults reduces the incidence of systemic inflammatory response syndrome and organ failure. Limited pediatric studies support correction of hypovolemia and/or circulatory compromise using 10-20 ml/kg boluses of isotonic crystalloid fluid. Although the literature is sparse regarding the rate of continued fluid replacement, the committee recommends patients receive 1.5-2 times maintenance intravenous fluid (IVF) with normal saline plus 5% dextrose for the first 24-48 hours. The rate of IVF administration should be adjusted based on volume status and urine output. IVF should be discontinued once the patient is able to maintain adequate hydration enterally. Cardiac, renal, and pulmonary complications of pancreatitis often present within the first 48 hours of illness and should prompt close monitoring with assessment of vital signs every four hours. The committee recommends monitoring serum electrolytes and renal function in the first 48 hours but does not offer guidance regarding the frequency of laboratory testing or the value of trending serum biomarkers.

Recommendation 3. Except in the presence of direct contraindications to use the gut, children with mild acute pancreatitis may benefit from early (within 48-72 hours of presentation) oral and enteral nutrition to decrease the length of stay (LOS) and the risk of organ dysfunction.

Adult studies suggest early enteral nutrition decreases complications and reduces LOS. Initiating enteral nutrition within 48 hours in children may have similar benefits. Several small pediatric studies have demonstrated a reduced LOS with early enteral feeds without an increase in complications. In a retrospective single-center study, children who were fed within the first 48 hours and received 1.5-2 times maintenance IVF had shorter LOS, less frequent intensive care admissions, and reduced severity of illness compared with those who were kept nil per os for the first 48 hours.⁵ Nasogastric or nasojejunal feeds may be initiated if a patient is unable to tolerate oral feeding. Parenteral nutrition should be reserved for children in whom enteral nutrition cannot be initiated within five to seven days.

Recommendation 4. Intravenous morphine or other opioids should be used for acute pancreatitis pain not responding to acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs).

Abdominal pain is the most common presenting symptom of pancreatitis, and pain control is an essential component of supportive care. There are no randomized trials identifying an optimal pain management regimen. The committee recommends the use of opioids for pain not controlled with acetaminophen and NSAIDs. Refractory pain may necessitate consultation with an acute pain specialist.

Recommendation 5. Routine use of prophylactic antibiotics, protease inhibitors, antioxidants, and probiotics is not recommended in acute pancreatitis.

Adult literature does not support routine use of antibiotics in acute pancreatitis, but their use may be beneficial in severe or recalcitrant cases. Pediatric literature neither confirms nor refutes this finding. The guideline does not recommend the use of antibiotics without signs of infection. Limited adult studies have shown protease inhibitors, antioxidants, and probiotics to be beneficial; however, no pediatric data support their use.

This guideline also discusses interventional and surgical procedures. Of note, biliary tract disease may necessitate endoscopic retrograde cholangiopancreatography or cholecystectomy. Such procedures should be considered in conjunction with subspecialty input.²

Methods in Preparing Guideline

The guideline development committee, funded by the NASPGHAN and the National Institutes of Diabetes and Digestive and Kidney Diseases, was composed of members of the NASPGHAN Pancreas Committee and included gastroenterologists from multiple sites.² Topics were selected via group discussion, and Medline searches included both adult and pediatric literature. Preliminary recommendations were presented at the 2016 World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Following revision, the 24 authors voted on each recommendation using a five-point Likert scale. A recommendation passed if 75% of the participants either agreed or strongly agreed with it. The authors reported no conflicts of interest.

Although the literature review was comprehensive, it lacked prospective pediatric studies and many of the recommendations were derived from adult research. The committee originally intended to grade the quality of evidence; however, the pediatric specific literature was underpowered and retrospective. Therefore, the committee opted to use consensus voting. The authors note that had the group used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, it would have returned grades of “low” or “very low” quality evidence.² The Hungarian Pancreatic Study Group and the European Pancreatic Club published a consensus guideline on the management of pediatric acute pancreatitis shortly after the NASPGHAN guideline, which offers similar conclusions.^2,6 The strength and generalizability of the NASPGHAN guideline are limited by its overreliance on adult literature, expert consensus, and small, retrospective pediatric studies to guide care.

This guideline highlights the need for pediatric research to guide the management of acute pancreatitis. The etiologies of pancreatitis in children are distinct from adults, where alcohol abuse and biliary disease are significant contributors.¹ Furthermore, age and environmental factors influence the presentation and clinical course.¹ Robust, prospective studies are needed to better understand the treatment outcomes of pediatric pancreatitis. Areas of further research include pediatric pancreatic severity scoring, ideal fluid composition and administration rate, enteral feed timing, optimal pain control, laboratory monitoring frequency, and adjuvant therapies.

Disclosures

Dr. Wall has nothing to disclose.

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

A 40-year-old woman with a history of opioid use disorder (OUD) on buprenorphine-naloxone treatment is admitted to medicine following incision and drainage of a large forearm abscess with surrounding cellulitis. The patient reports severe pain following the procedure, which is not relieved by ibuprofen. The admitting hospitalist orders a pain regimen for the patient, which includes oral and intravenous hydromorphone and discontinues the patient’s buprenorphine-naloxone so that the short-acting opioids can take effect.

Medications to treat OUD include methadone, buprenorphine, and extended-release naltrexone. Buprenorphine is a Schedule III medication under the United States Food and Drug Administration that reduces opioid cravings, subsequently decreasing drug use¹ and opioid-related overdose deaths.² It has a favorable safety profile and can be prescribed for OUD in an office-based, outpatient setting since the Drug Addiction Treatment Act of 2000 (DATA 2000). Due to extensive first-pass metabolism, buprenorphine for OUD is typically administered sublingually, either alone or in a fixed combination with naloxone.

Buprenorphine is a partial opioid agonist with a long half-life and high affinity for the mu opioid receptor. Given these properties, prior recommendations assumed that buprenorphine blocked the effectiveness of additional opioid agonists.^3,4 In 2004, guidelines by the Department of Health and Human Service Center for Substance Abuse Treatment recommended discontinuing buprenorphine in patients taking opioid pain medications.⁵ These suggestions were based on limited case reports describing difficulty controlling pain in patients with OUD with a high opioid tolerance who were receiving buprenorphine.⁶

Providers may hold buprenorphine when treating acute pain out of concern it could precipitate withdrawal by displacing full opioid agonists from the mu receptor. Providers may also believe that the naloxone component in the most commonly prescribed formulation, buprenorphine-naloxone, blocks the effects of opioid analgesics. Evolving understanding of buprenorphine pharmacology and the absence of high-quality evidence has resulted in providers holding buprenorphine in the setting of acute pain.

Finally, providers without dedicated training may feel they lack the necessary qualifications to prescribe buprenorphine in the inpatient setting. DATA 2000 requires mandatory X waiver training for physicians, nurse practitioners, and physician assistants to prescribe outpatient buprenorphine for OUD treatment outside of specialized opioid treatment programs.

Despite buprenorphine’s high affinity at the mu receptor, additional receptors remain available for full opioid agonists to bind and activate,⁶ providing effective pain relief even in patients using buprenorphine. In contrast to the 2004 Department of Health and Human Service guidelines, subsequent clinical studies have demonstrated that concurrent use of opioid analgesics is effective for patients maintained on buprenorphine, similar to patients on other forms of OUD treatment such as methadone.^7,8

Precipitated withdrawal only occurs when buprenorphine is newly introduced to patients with already circulating opioids. Patients receiving buprenorphine-naloxone can also be exposed to opioids without precipitated withdrawal from the naloxone component, as naloxone is not absorbed via sublingual or buccal administration, but only present in the formulation to dissuade intravenous administration of the medication.

Even in the perioperative period, there is insufficient evidence to support the discontinuation of buprenorphine.⁹ Studies in this patient population have found that patients receiving buprenorphine may require higher doses of short-acting opioids to achieve adequate analgesia, but they experience similar pain control, lengths of stay, and functional outcomes to controls.¹⁰ Despite variable perioperative management of buprenorphine,¹¹ protocols at major medical centers now recommend continuing or dose adjusting buprenorphine in the perioperative period rather than discontinuing.^12-14

Patients physically dependent on opioid agonists, including buprenorphine, must be maintained on a daily equivalent opioid dose to avoid experiencing withdrawal. This maintenance requirement must be met before any analgesic effect for acute pain is obtained with additional opioids. Temporarily discontinuing buprenorphine introduces unnecessary complexity to a hospitalization, places the patient at risk of exacerbation of pain, opioid withdrawal, and predisposes the patient to return to use and overdose if not resumed before hospital discharge.⁵

Finally, clinicians do not require additional training or an X waiver to administer buprenorphine to hospitalized patients. These requirements are limited to providers managing buprenorphine in the outpatient setting or those prescribing buprenorphine to patients to take postdischarge. Hospitalists frequently prescribe opioid medications in the inpatient setting with similar or greater safety risk profiles to buprenorphine.

Providers may consider holding buprenorphine if a patient with OUD has not been taking buprenorphine before hospitalization and has severe acute pain needs. This history can be confirmed with the patient and the state’s online prescription drug monitoring program. If further clarification is needed, this can be accomplished with a pharmacist and urine testing or by verifying with the patient’s opioid treatment program, as some programs provide directly administered buprenorphine.

In cases where a patient may have stopped buprenorphine before admission but wants to restart it in the hospital, it is essential to ascertain when the patient last used an opioid. The buprenorphine reinduction should be timed to a sufficient number of hours since last opioid use and/or to when the patient shows signs of active withdrawal. The re-induction can take place before, during, or after an acute pain episode, depending on the individual circumstances.

Patient preference is extremely important in the management of both pain and OUD. After shared decision-making, some patients may ultimately opt to hold buprenorphine in certain situations or switch to an alternative treatment, such as methadone, during their hospitalization. Such adjustments should be made in conjunction with the patient, primary care provider, and pain or addiction medicine specialty consultation.

For patients on buprenorphine admitted to the hospital with anticipated or unanticipated acute pain needs, hospitalists should continue buprenorphine. Continuation of buprenorphine meets a patient’s baseline opioid requirement while still allowing the use of additional short-acting opioid agonists as needed for pain.¹⁵

As with all pain, multimodal pain management should be provided with adjunctive medications such as acetaminophen, nonsteroidal anti-inflammatory drugs, neuropathic agents, topical analgesics, and regional anesthesia.⁸

Acute pain can be addressed by taking advantage of buprenorphine’s analgesic effects and adding additional short-acting opioids if needed.¹⁵ Several options are available, including:

1. Continuing daily buprenorphine and prescribing short-acting opioid agonists, preferably those with high intrinsic activity at the mu receptor (such as morphine, fentanyl, or hydromorphone). Full opioid agonist doses to achieve analgesia for patients on buprenorphine will be higher than in opioid naïve patients due to tolerance.¹⁶

2 .Dividing the total daily buprenorphine dose into three or four times per day dosing, since buprenorphine provides an analgesic effect lasting six to eight hours. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

3. Temporarily increasing the total daily buprenorphine dose and dividing into three or four times per day dosing, as above. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

It is essential to make a clear plan with the patient for initiation and discontinuation of short-acting opioid agonists or buprenorphine changes. Patients on buprenorphine should be managed collaboratively with the primary care provider or addiction specialist to coordinate prescribing and follow-up after discharge.

• Continue outpatient buprenorphine treatment for patients admitted with acute pain.
• Use adjunctive nonopioid pain medications and nonpharmacologic modalities to address acute pain.
• Adjust buprenorphine to address acute pain by dividing the total daily amount into three or four times a day dosing, and/or up-titrate the buprenorphine dose (federal prescribing regulations recommend a maximum of 24 mg daily, but state regulations may vary).
• Add short-acting opioid agonists on an as-needed basis in conjunction with a defined plan to discontinue short-acting opioid agonists to avoid a return to use.
• Make plans collaboratively with the patient and outpatient provider, and communicate medication changes and plan at discharge.

Concerning our case, the hospitalist can continue the patient’s buprenorphine-naloxone, even with her acute pain needs. The patient has a baseline opioid requirement, fulfilled by continuing buprenorphine. Additional short-acting opioid agonists, such as hydromorphone, will provide analgesia for the patient, though the clinician should be aware that higher doses might be required. The practice of holding buprenorphine during episodes of acute pain is not supported by current evidence and may predispose to inadequate analgesia, opioid withdrawal, and risk of return to use and death.²

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

Disclosures

The authors report no conflicts of interest.

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

A 40-year-old woman with a history of opioid use disorder (OUD) on buprenorphine-naloxone treatment is admitted to medicine following incision and drainage of a large forearm abscess with surrounding cellulitis. The patient reports severe pain following the procedure, which is not relieved by ibuprofen. The admitting hospitalist orders a pain regimen for the patient, which includes oral and intravenous hydromorphone and discontinues the patient’s buprenorphine-naloxone so that the short-acting opioids can take effect.

Medications to treat OUD include methadone, buprenorphine, and extended-release naltrexone. Buprenorphine is a Schedule III medication under the United States Food and Drug Administration that reduces opioid cravings, subsequently decreasing drug use¹ and opioid-related overdose deaths.² It has a favorable safety profile and can be prescribed for OUD in an office-based, outpatient setting since the Drug Addiction Treatment Act of 2000 (DATA 2000). Due to extensive first-pass metabolism, buprenorphine for OUD is typically administered sublingually, either alone or in a fixed combination with naloxone.

Buprenorphine is a partial opioid agonist with a long half-life and high affinity for the mu opioid receptor. Given these properties, prior recommendations assumed that buprenorphine blocked the effectiveness of additional opioid agonists.^3,4 In 2004, guidelines by the Department of Health and Human Service Center for Substance Abuse Treatment recommended discontinuing buprenorphine in patients taking opioid pain medications.⁵ These suggestions were based on limited case reports describing difficulty controlling pain in patients with OUD with a high opioid tolerance who were receiving buprenorphine.⁶

Providers may hold buprenorphine when treating acute pain out of concern it could precipitate withdrawal by displacing full opioid agonists from the mu receptor. Providers may also believe that the naloxone component in the most commonly prescribed formulation, buprenorphine-naloxone, blocks the effects of opioid analgesics. Evolving understanding of buprenorphine pharmacology and the absence of high-quality evidence has resulted in providers holding buprenorphine in the setting of acute pain.

Finally, providers without dedicated training may feel they lack the necessary qualifications to prescribe buprenorphine in the inpatient setting. DATA 2000 requires mandatory X waiver training for physicians, nurse practitioners, and physician assistants to prescribe outpatient buprenorphine for OUD treatment outside of specialized opioid treatment programs.

Despite buprenorphine’s high affinity at the mu receptor, additional receptors remain available for full opioid agonists to bind and activate,⁶ providing effective pain relief even in patients using buprenorphine. In contrast to the 2004 Department of Health and Human Service guidelines, subsequent clinical studies have demonstrated that concurrent use of opioid analgesics is effective for patients maintained on buprenorphine, similar to patients on other forms of OUD treatment such as methadone.^7,8

Precipitated withdrawal only occurs when buprenorphine is newly introduced to patients with already circulating opioids. Patients receiving buprenorphine-naloxone can also be exposed to opioids without precipitated withdrawal from the naloxone component, as naloxone is not absorbed via sublingual or buccal administration, but only present in the formulation to dissuade intravenous administration of the medication.

Even in the perioperative period, there is insufficient evidence to support the discontinuation of buprenorphine.⁹ Studies in this patient population have found that patients receiving buprenorphine may require higher doses of short-acting opioids to achieve adequate analgesia, but they experience similar pain control, lengths of stay, and functional outcomes to controls.¹⁰ Despite variable perioperative management of buprenorphine,¹¹ protocols at major medical centers now recommend continuing or dose adjusting buprenorphine in the perioperative period rather than discontinuing.^12-14

Patients physically dependent on opioid agonists, including buprenorphine, must be maintained on a daily equivalent opioid dose to avoid experiencing withdrawal. This maintenance requirement must be met before any analgesic effect for acute pain is obtained with additional opioids. Temporarily discontinuing buprenorphine introduces unnecessary complexity to a hospitalization, places the patient at risk of exacerbation of pain, opioid withdrawal, and predisposes the patient to return to use and overdose if not resumed before hospital discharge.⁵

Finally, clinicians do not require additional training or an X waiver to administer buprenorphine to hospitalized patients. These requirements are limited to providers managing buprenorphine in the outpatient setting or those prescribing buprenorphine to patients to take postdischarge. Hospitalists frequently prescribe opioid medications in the inpatient setting with similar or greater safety risk profiles to buprenorphine.

Providers may consider holding buprenorphine if a patient with OUD has not been taking buprenorphine before hospitalization and has severe acute pain needs. This history can be confirmed with the patient and the state’s online prescription drug monitoring program. If further clarification is needed, this can be accomplished with a pharmacist and urine testing or by verifying with the patient’s opioid treatment program, as some programs provide directly administered buprenorphine.

In cases where a patient may have stopped buprenorphine before admission but wants to restart it in the hospital, it is essential to ascertain when the patient last used an opioid. The buprenorphine reinduction should be timed to a sufficient number of hours since last opioid use and/or to when the patient shows signs of active withdrawal. The re-induction can take place before, during, or after an acute pain episode, depending on the individual circumstances.

Patient preference is extremely important in the management of both pain and OUD. After shared decision-making, some patients may ultimately opt to hold buprenorphine in certain situations or switch to an alternative treatment, such as methadone, during their hospitalization. Such adjustments should be made in conjunction with the patient, primary care provider, and pain or addiction medicine specialty consultation.

For patients on buprenorphine admitted to the hospital with anticipated or unanticipated acute pain needs, hospitalists should continue buprenorphine. Continuation of buprenorphine meets a patient’s baseline opioid requirement while still allowing the use of additional short-acting opioid agonists as needed for pain.¹⁵

As with all pain, multimodal pain management should be provided with adjunctive medications such as acetaminophen, nonsteroidal anti-inflammatory drugs, neuropathic agents, topical analgesics, and regional anesthesia.⁸

Acute pain can be addressed by taking advantage of buprenorphine’s analgesic effects and adding additional short-acting opioids if needed.¹⁵ Several options are available, including:

1. Continuing daily buprenorphine and prescribing short-acting opioid agonists, preferably those with high intrinsic activity at the mu receptor (such as morphine, fentanyl, or hydromorphone). Full opioid agonist doses to achieve analgesia for patients on buprenorphine will be higher than in opioid naïve patients due to tolerance.¹⁶

2 .Dividing the total daily buprenorphine dose into three or four times per day dosing, since buprenorphine provides an analgesic effect lasting six to eight hours. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

3. Temporarily increasing the total daily buprenorphine dose and dividing into three or four times per day dosing, as above. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

It is essential to make a clear plan with the patient for initiation and discontinuation of short-acting opioid agonists or buprenorphine changes. Patients on buprenorphine should be managed collaboratively with the primary care provider or addiction specialist to coordinate prescribing and follow-up after discharge.

• Continue outpatient buprenorphine treatment for patients admitted with acute pain.
• Use adjunctive nonopioid pain medications and nonpharmacologic modalities to address acute pain.
• Adjust buprenorphine to address acute pain by dividing the total daily amount into three or four times a day dosing, and/or up-titrate the buprenorphine dose (federal prescribing regulations recommend a maximum of 24 mg daily, but state regulations may vary).
• Add short-acting opioid agonists on an as-needed basis in conjunction with a defined plan to discontinue short-acting opioid agonists to avoid a return to use.
• Make plans collaboratively with the patient and outpatient provider, and communicate medication changes and plan at discharge.

Concerning our case, the hospitalist can continue the patient’s buprenorphine-naloxone, even with her acute pain needs. The patient has a baseline opioid requirement, fulfilled by continuing buprenorphine. Additional short-acting opioid agonists, such as hydromorphone, will provide analgesia for the patient, though the clinician should be aware that higher doses might be required. The practice of holding buprenorphine during episodes of acute pain is not supported by current evidence and may predispose to inadequate analgesia, opioid withdrawal, and risk of return to use and death.²

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

Disclosures

The authors report no conflicts of interest.

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

A 40-year-old woman with a history of opioid use disorder (OUD) on buprenorphine-naloxone treatment is admitted to medicine following incision and drainage of a large forearm abscess with surrounding cellulitis. The patient reports severe pain following the procedure, which is not relieved by ibuprofen. The admitting hospitalist orders a pain regimen for the patient, which includes oral and intravenous hydromorphone and discontinues the patient’s buprenorphine-naloxone so that the short-acting opioids can take effect.

Medications to treat OUD include methadone, buprenorphine, and extended-release naltrexone. Buprenorphine is a Schedule III medication under the United States Food and Drug Administration that reduces opioid cravings, subsequently decreasing drug use¹ and opioid-related overdose deaths.² It has a favorable safety profile and can be prescribed for OUD in an office-based, outpatient setting since the Drug Addiction Treatment Act of 2000 (DATA 2000). Due to extensive first-pass metabolism, buprenorphine for OUD is typically administered sublingually, either alone or in a fixed combination with naloxone.

Buprenorphine is a partial opioid agonist with a long half-life and high affinity for the mu opioid receptor. Given these properties, prior recommendations assumed that buprenorphine blocked the effectiveness of additional opioid agonists.^3,4 In 2004, guidelines by the Department of Health and Human Service Center for Substance Abuse Treatment recommended discontinuing buprenorphine in patients taking opioid pain medications.⁵ These suggestions were based on limited case reports describing difficulty controlling pain in patients with OUD with a high opioid tolerance who were receiving buprenorphine.⁶

Providers may hold buprenorphine when treating acute pain out of concern it could precipitate withdrawal by displacing full opioid agonists from the mu receptor. Providers may also believe that the naloxone component in the most commonly prescribed formulation, buprenorphine-naloxone, blocks the effects of opioid analgesics. Evolving understanding of buprenorphine pharmacology and the absence of high-quality evidence has resulted in providers holding buprenorphine in the setting of acute pain.

Finally, providers without dedicated training may feel they lack the necessary qualifications to prescribe buprenorphine in the inpatient setting. DATA 2000 requires mandatory X waiver training for physicians, nurse practitioners, and physician assistants to prescribe outpatient buprenorphine for OUD treatment outside of specialized opioid treatment programs.

Despite buprenorphine’s high affinity at the mu receptor, additional receptors remain available for full opioid agonists to bind and activate,⁶ providing effective pain relief even in patients using buprenorphine. In contrast to the 2004 Department of Health and Human Service guidelines, subsequent clinical studies have demonstrated that concurrent use of opioid analgesics is effective for patients maintained on buprenorphine, similar to patients on other forms of OUD treatment such as methadone.^7,8

Precipitated withdrawal only occurs when buprenorphine is newly introduced to patients with already circulating opioids. Patients receiving buprenorphine-naloxone can also be exposed to opioids without precipitated withdrawal from the naloxone component, as naloxone is not absorbed via sublingual or buccal administration, but only present in the formulation to dissuade intravenous administration of the medication.

Even in the perioperative period, there is insufficient evidence to support the discontinuation of buprenorphine.⁹ Studies in this patient population have found that patients receiving buprenorphine may require higher doses of short-acting opioids to achieve adequate analgesia, but they experience similar pain control, lengths of stay, and functional outcomes to controls.¹⁰ Despite variable perioperative management of buprenorphine,¹¹ protocols at major medical centers now recommend continuing or dose adjusting buprenorphine in the perioperative period rather than discontinuing.^12-14

Patients physically dependent on opioid agonists, including buprenorphine, must be maintained on a daily equivalent opioid dose to avoid experiencing withdrawal. This maintenance requirement must be met before any analgesic effect for acute pain is obtained with additional opioids. Temporarily discontinuing buprenorphine introduces unnecessary complexity to a hospitalization, places the patient at risk of exacerbation of pain, opioid withdrawal, and predisposes the patient to return to use and overdose if not resumed before hospital discharge.⁵

Finally, clinicians do not require additional training or an X waiver to administer buprenorphine to hospitalized patients. These requirements are limited to providers managing buprenorphine in the outpatient setting or those prescribing buprenorphine to patients to take postdischarge. Hospitalists frequently prescribe opioid medications in the inpatient setting with similar or greater safety risk profiles to buprenorphine.

Providers may consider holding buprenorphine if a patient with OUD has not been taking buprenorphine before hospitalization and has severe acute pain needs. This history can be confirmed with the patient and the state’s online prescription drug monitoring program. If further clarification is needed, this can be accomplished with a pharmacist and urine testing or by verifying with the patient’s opioid treatment program, as some programs provide directly administered buprenorphine.

In cases where a patient may have stopped buprenorphine before admission but wants to restart it in the hospital, it is essential to ascertain when the patient last used an opioid. The buprenorphine reinduction should be timed to a sufficient number of hours since last opioid use and/or to when the patient shows signs of active withdrawal. The re-induction can take place before, during, or after an acute pain episode, depending on the individual circumstances.

Patient preference is extremely important in the management of both pain and OUD. After shared decision-making, some patients may ultimately opt to hold buprenorphine in certain situations or switch to an alternative treatment, such as methadone, during their hospitalization. Such adjustments should be made in conjunction with the patient, primary care provider, and pain or addiction medicine specialty consultation.

For patients on buprenorphine admitted to the hospital with anticipated or unanticipated acute pain needs, hospitalists should continue buprenorphine. Continuation of buprenorphine meets a patient’s baseline opioid requirement while still allowing the use of additional short-acting opioid agonists as needed for pain.¹⁵

As with all pain, multimodal pain management should be provided with adjunctive medications such as acetaminophen, nonsteroidal anti-inflammatory drugs, neuropathic agents, topical analgesics, and regional anesthesia.⁸

Acute pain can be addressed by taking advantage of buprenorphine’s analgesic effects and adding additional short-acting opioids if needed.¹⁵ Several options are available, including:

1. Continuing daily buprenorphine and prescribing short-acting opioid agonists, preferably those with high intrinsic activity at the mu receptor (such as morphine, fentanyl, or hydromorphone). Full opioid agonist doses to achieve analgesia for patients on buprenorphine will be higher than in opioid naïve patients due to tolerance.¹⁶

2 .Dividing the total daily buprenorphine dose into three or four times per day dosing, since buprenorphine provides an analgesic effect lasting six to eight hours. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

3. Temporarily increasing the total daily buprenorphine dose and dividing into three or four times per day dosing, as above. Short-acting opioid agonists can still be prescribed on an as-needed basis for additional pain needs.

It is essential to make a clear plan with the patient for initiation and discontinuation of short-acting opioid agonists or buprenorphine changes. Patients on buprenorphine should be managed collaboratively with the primary care provider or addiction specialist to coordinate prescribing and follow-up after discharge.

• Continue outpatient buprenorphine treatment for patients admitted with acute pain.
• Use adjunctive nonopioid pain medications and nonpharmacologic modalities to address acute pain.
• Adjust buprenorphine to address acute pain by dividing the total daily amount into three or four times a day dosing, and/or up-titrate the buprenorphine dose (federal prescribing regulations recommend a maximum of 24 mg daily, but state regulations may vary).
• Add short-acting opioid agonists on an as-needed basis in conjunction with a defined plan to discontinue short-acting opioid agonists to avoid a return to use.
• Make plans collaboratively with the patient and outpatient provider, and communicate medication changes and plan at discharge.

Concerning our case, the hospitalist can continue the patient’s buprenorphine-naloxone, even with her acute pain needs. The patient has a baseline opioid requirement, fulfilled by continuing buprenorphine. Additional short-acting opioid agonists, such as hydromorphone, will provide analgesia for the patient, though the clinician should be aware that higher doses might be required. The practice of holding buprenorphine during episodes of acute pain is not supported by current evidence and may predispose to inadequate analgesia, opioid withdrawal, and risk of return to use and death.²

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

Disclosures

The authors report no conflicts of interest.

Elevated serum troponin clearly does not equal myocardial infarction (MI). This was the strong message in the 2018 publication of the Fourth Universal Definition of Myocardial Infarction¹ (4UDMI), the first update to the international consensus document since 2012.

Most clinicians have learned how to accurately diagnose the classic Type 1 MI (T1MI) due to atherosclerotic plaque rupture; however, elevated troponin in the absence of T1MI is increasingly common due to more frequent and less discriminate troponin testing.² Patients with elevated troponin in the absence of T1MI have traditionally created confusion and variability in diagnosis, management, and documentation. Interpretation and management of elevated troponin in the absence of T1MI has become difficult.

In this clinical practice update, we aim to review the updated definition of Type 2 MI (T2MI) and nonischemic myocardial injury (NIMI), since these are the two predominant diagnoses among patients with elevated troponin in the absence of T1MI. We also provide a clinical framework for clinicians to think through elevated serum cardiac troponin levels and identify opportunities for quality improvement around this critical issue.

The presence of an elevated serum troponin level is a critical component in determining the presence of cardiac myocyte injury and possible infarction. Myocardial injury is defined as the presence of serum troponin above the 99th percentile of the upper reference limit (URL), the absolute value of which varies by assay and which applies to traditional and highly sensitive subtypes. Myocardial injury can be confusing to assess, as it can be acute or chronic.

When troponin levels are elevated but stable, this is indicative of chronic (usually nonischemic) myocardial injury, as seen, for example, in patients who have end-stage renal disease. The presence of acute injury requires a change in the troponin value—specifically a rise and/or fall in troponin levels with serial measurements. What constitutes a significant “rise and/or fall” is a matter of some debate and is not precisely defined in the 4UDMI. The percent change in the troponin value over time (relative delta) is listed as part of the criteria for acute injury when the change is greater than or equal to 20%;¹ however, clinicians should be aware that absolute delta in troponin (the change in ng/dL) has better performance characteristics³ in diagnosing acute myocardial injury. Regardless of whether clinicians use relative or absolute changes in the serum troponin level, clinical evaluation of patients with acute injury is critical to establishing whether the injury is ischemic (MI) or nonischemic (NIMI). The presence of at least one of the following is necessary to meet the current criteria for myocardial ischemia according to the fourth universal definition: new ischemic symptoms (eg, chest pain, dyspnea, etc.), new ischemic changes in the patient’s electrocardiogram (eg, new ST segment depression in leads II, III, and aVF), or cardiac imaging changes consistent with ischemic injury (eg, new wall motion abnormality in the inferior wall on echocardiography).

Following diagnosis of MI based on elevated troponin and new symptoms or signs, the cause of MI should then be determined. Type 1 MI remains defined as MI caused by atherosclerotic plaque disruption in a patient with coronary artery disease (CAD). Type 2 MI is not caused by plaque disruption but is due to a mismatch between oxygen supply and demand unrelated to acute atherothrombosis. T2MI is an ischemic myocardial injury traceable to some other illness that leads to inadequate myocyte oxygenation. Causes of T2MI are numerous, can overlap with nonischemic injury, and can include severe anemia, septic shock, rapid atrial fibrillation, and coronary dissection. While CAD may be present in patients with T2MI, it is not a requirement, and an increased demand for, or reduced supply of, myocyte oxygen alone can be sufficient to cause MI.

In the absence of clinical signs or symptoms of cardiac ischemia, clinicians should categorize patients as having a nonischemic myocardial injury. There is significant overlap between causes of T2MI and NIMI, for example, sepsis could cause either T2MI or NIMI. What distinguishes these two entities is whether the signs and symptoms for myocardial ischemia as outlined above are present. If these signs or symptoms are present, the diagnosis is T2MI. If no clinical signs or symptoms of ischemia are present, the diagnosis is NIMI. The assessment of the clinician, using all available clinical information, is pivotal. The characteristics of the three major types of myocardial injury are depicted in the Figure.

Proper distinction between infarction or injury without infarction is central to proper evaluation, treatment, and eventual documentation in patients with elevated troponin levels. In the case of T2MI and NIMI, identifying what underlying illness is causing the troponin elevation is essential for acute management.

Evaluation

Troponin elevation is associated with an elevated risk for major adverse cardiovascular events, regardless of etiology.⁴ While patients with suspected T1MI are most often evaluated by coronary angiography, this may not be necessary for patients with T2MI or NIMI. Developing an evaluation strategy for patients with T2MI or NIMI requires understanding the underlying etiology of myocardial injury. In patients with septic shock for example, there are many potential mechanisms for cardiac myocyte injury, many of which are nonischemic (eg, cytokine-mediated).⁵ Prompt evaluation and treatment of septic shock, therefore, often leads to resolution of cardiac dysfunction, and ischemic evaluation may not be necessary.⁶ In many cases of T2MI or NIMI, waiting for an acute underlying illness to resolve is necessary before deciding whether ischemic evaluation is appropriate. It is important that this decision is deferred but not forgotten though as patients with T2MI or NIMI may benefit from further cardiac evaluation. There are no society recommendations and minimal evidence to guide this evaluation, but clinical trials testing different evaluation strategies are underway.⁷ Until an optimal evidence-based evaluation strategy becomes clear, clinicians should focus on two key principles: first, determine and treat the underlying etiology; second, identify patients with traditional risk factors for CAD and consider further evaluation with either coronary angiography or cardiac imaging. Referral to a cardiologist for assistance with the latter issue, especially for challenging or equivocal cases, is encouraged.

Treatment

While T1MI therapies have a strong evidence base with high rates of appropriate treatment, there are relatively few evidence-based therapies for T2MI and NIMI. The benefits of traditional T1MI therapies should be considered in terms of each therapy’s risk-benefit profile. Among patients with T2MI or NIMI in whom atherosclerotic plaque rupture is unlikely, or in whom bleeding risk is high, antithrombotic agents such as unfractionated heparin and dual antiplatelet therapy represent low value and potentially harmful therapies.⁸ Conversely, patients with multiple risk factors for CAD may benefit from low-risk guideline directed medical therapies such as HMGCoA reductase inhibitors (ie, “statins”). Recent data suggest that lipid-lowering therapies may even be beneficial for preventing T2MI.⁹

Given the lack of evidence for therapies to treat patients with T2MI or NIMI, clinical judgment remains central to creating an optimal management plan. Clinicians should consider consultation with a cardiologist any time there is ambiguity in whether the diagnosis is T1MI or T2MI. For example, postoperative patients represent a particularly challenging clinical scenario due to the difficulty of assessing ischemic signs and symptoms in the operating room. In this setting, early evaluation by a cardiologist has been shown to improve outcomes.¹⁰

Documentation

Documentation of non-ST elevation MI (NSTEMI) for every case of elevated troponin, rather than using the more specific T1MI, T2MI, or NIMI terminology, can have adverse consequences for health systems. From a coding perspective, the terms STEMI and NSTEMI mean T1MI, and the ICD-10 codes used to identify T1MI patients for value-focused programs frequently include patients with T2MI and NIMI due to imprecise documentation.¹¹ When T2MI and NIMI are imprecisely documented as NSTEMI, health systems and clinicians are held to the T1MI care standards. This can negatively skew the performance of a health system or individual clinician because T2MI and NIMI patients have worse outcomes than T1MI patients.⁴ Inaccurate categorization of patients can lead to inaccurate quality and registry reporting, which may hinder the ability of health systems to monitor and implement quality improvement programs for MI patients. The distinction between T1MI and T2MI in documentation is all the more important now that a new ICD-10 code exists for T2MI (I21.A1), which allows clinicians to more precisely identify these patients, both clinically and administratively, as distinct from T1MI patients.¹² While there is no similarly specific ICD-10 code for NIMI, using the appropriate terminology in documentation should prompt coding personnel to use a code for “other abnormal findings of blood chemistry,” reflecting cardiac biomarker elevation (R79.89), rather than using one of the T1MI codes. Clinicians may not be able to determine the etiology of troponin elevation in the initial phase of a hospitalization, but a definitive diagnosis should be documented in the discharge summary.

From the patient perspective, documentation using STEMI and NSTEMI can mislead clinicians, given that this terminology does not specify the underlying cause (ie, plaque rupture or oxygen supply-demand mismatch), potentially leading to delayed initiation of appropriate therapy. Incorrect documentation, using STEMI/NSTEMI language or incorrectly labeling T2MI and NIMI, may lead patients to believe they have had a heart attack when they had myocardial injury instead. This may lead to unnecessary anxiety and change their interactions with the health system. These patients may be started on unnecessary therapies, have inaccurate preoperative evaluations, and be labeled with a preexisting condition for the rest of their lives.

Opportunities for Quality Improvement

Systems-based quality improvement can help to ensure that patients with NIMI and T2MI are labeled appropriately and receive the proper treatment. Clinical education is the cornerstone of such efforts. Hospital medicine practitioners looking for support in understanding this issue might first partner with cardiology colleagues who may already have training materials available. Billing and coding personnel stand to benefit from greater orientation to this topic considering the complexities and errors in the coding of MI. In an attempt to help nonclinical coding personnel, leaders in the American College of Cardiology have advocated for use of the term “non-MI troponin elevation” (nMITE)¹³ to describe NIMI patients. Finally, we see an important role for EHR-embedded decision support tools to facilitate appropriate documentation and management of patients with elevated troponin. A potential care pathway, for example, could be created in partnership between hospital medicine and cardiology providers to identify which patients would benefit from cardiologist consultation.

Understanding the definitions of T1MI, T2MI, and NIMI will help clinicians to better identify the appropriate clinical care and consultation strategy for patients with elevated cardiac troponin. There are relatively few published quality improvement initiatives to help guide clinicians through these nuanced distinctions, but there is great potential in such approaches to help clinicians provide the highest value care possible.

Disclosures

No authors have any conflict of interest, financial or otherwise, to declare regarding this study.

Funding

Dr. Levy receives funding from National Institutes of Health (NIH) T32 Training Grant 5T32-HL007822.

Elevated serum troponin clearly does not equal myocardial infarction (MI). This was the strong message in the 2018 publication of the Fourth Universal Definition of Myocardial Infarction¹ (4UDMI), the first update to the international consensus document since 2012.

Most clinicians have learned how to accurately diagnose the classic Type 1 MI (T1MI) due to atherosclerotic plaque rupture; however, elevated troponin in the absence of T1MI is increasingly common due to more frequent and less discriminate troponin testing.² Patients with elevated troponin in the absence of T1MI have traditionally created confusion and variability in diagnosis, management, and documentation. Interpretation and management of elevated troponin in the absence of T1MI has become difficult.

In this clinical practice update, we aim to review the updated definition of Type 2 MI (T2MI) and nonischemic myocardial injury (NIMI), since these are the two predominant diagnoses among patients with elevated troponin in the absence of T1MI. We also provide a clinical framework for clinicians to think through elevated serum cardiac troponin levels and identify opportunities for quality improvement around this critical issue.

The presence of an elevated serum troponin level is a critical component in determining the presence of cardiac myocyte injury and possible infarction. Myocardial injury is defined as the presence of serum troponin above the 99th percentile of the upper reference limit (URL), the absolute value of which varies by assay and which applies to traditional and highly sensitive subtypes. Myocardial injury can be confusing to assess, as it can be acute or chronic.

When troponin levels are elevated but stable, this is indicative of chronic (usually nonischemic) myocardial injury, as seen, for example, in patients who have end-stage renal disease. The presence of acute injury requires a change in the troponin value—specifically a rise and/or fall in troponin levels with serial measurements. What constitutes a significant “rise and/or fall” is a matter of some debate and is not precisely defined in the 4UDMI. The percent change in the troponin value over time (relative delta) is listed as part of the criteria for acute injury when the change is greater than or equal to 20%;¹ however, clinicians should be aware that absolute delta in troponin (the change in ng/dL) has better performance characteristics³ in diagnosing acute myocardial injury. Regardless of whether clinicians use relative or absolute changes in the serum troponin level, clinical evaluation of patients with acute injury is critical to establishing whether the injury is ischemic (MI) or nonischemic (NIMI). The presence of at least one of the following is necessary to meet the current criteria for myocardial ischemia according to the fourth universal definition: new ischemic symptoms (eg, chest pain, dyspnea, etc.), new ischemic changes in the patient’s electrocardiogram (eg, new ST segment depression in leads II, III, and aVF), or cardiac imaging changes consistent with ischemic injury (eg, new wall motion abnormality in the inferior wall on echocardiography).

Following diagnosis of MI based on elevated troponin and new symptoms or signs, the cause of MI should then be determined. Type 1 MI remains defined as MI caused by atherosclerotic plaque disruption in a patient with coronary artery disease (CAD). Type 2 MI is not caused by plaque disruption but is due to a mismatch between oxygen supply and demand unrelated to acute atherothrombosis. T2MI is an ischemic myocardial injury traceable to some other illness that leads to inadequate myocyte oxygenation. Causes of T2MI are numerous, can overlap with nonischemic injury, and can include severe anemia, septic shock, rapid atrial fibrillation, and coronary dissection. While CAD may be present in patients with T2MI, it is not a requirement, and an increased demand for, or reduced supply of, myocyte oxygen alone can be sufficient to cause MI.

In the absence of clinical signs or symptoms of cardiac ischemia, clinicians should categorize patients as having a nonischemic myocardial injury. There is significant overlap between causes of T2MI and NIMI, for example, sepsis could cause either T2MI or NIMI. What distinguishes these two entities is whether the signs and symptoms for myocardial ischemia as outlined above are present. If these signs or symptoms are present, the diagnosis is T2MI. If no clinical signs or symptoms of ischemia are present, the diagnosis is NIMI. The assessment of the clinician, using all available clinical information, is pivotal. The characteristics of the three major types of myocardial injury are depicted in the Figure.

Proper distinction between infarction or injury without infarction is central to proper evaluation, treatment, and eventual documentation in patients with elevated troponin levels. In the case of T2MI and NIMI, identifying what underlying illness is causing the troponin elevation is essential for acute management.

Evaluation

Troponin elevation is associated with an elevated risk for major adverse cardiovascular events, regardless of etiology.⁴ While patients with suspected T1MI are most often evaluated by coronary angiography, this may not be necessary for patients with T2MI or NIMI. Developing an evaluation strategy for patients with T2MI or NIMI requires understanding the underlying etiology of myocardial injury. In patients with septic shock for example, there are many potential mechanisms for cardiac myocyte injury, many of which are nonischemic (eg, cytokine-mediated).⁵ Prompt evaluation and treatment of septic shock, therefore, often leads to resolution of cardiac dysfunction, and ischemic evaluation may not be necessary.⁶ In many cases of T2MI or NIMI, waiting for an acute underlying illness to resolve is necessary before deciding whether ischemic evaluation is appropriate. It is important that this decision is deferred but not forgotten though as patients with T2MI or NIMI may benefit from further cardiac evaluation. There are no society recommendations and minimal evidence to guide this evaluation, but clinical trials testing different evaluation strategies are underway.⁷ Until an optimal evidence-based evaluation strategy becomes clear, clinicians should focus on two key principles: first, determine and treat the underlying etiology; second, identify patients with traditional risk factors for CAD and consider further evaluation with either coronary angiography or cardiac imaging. Referral to a cardiologist for assistance with the latter issue, especially for challenging or equivocal cases, is encouraged.

Treatment

While T1MI therapies have a strong evidence base with high rates of appropriate treatment, there are relatively few evidence-based therapies for T2MI and NIMI. The benefits of traditional T1MI therapies should be considered in terms of each therapy’s risk-benefit profile. Among patients with T2MI or NIMI in whom atherosclerotic plaque rupture is unlikely, or in whom bleeding risk is high, antithrombotic agents such as unfractionated heparin and dual antiplatelet therapy represent low value and potentially harmful therapies.⁸ Conversely, patients with multiple risk factors for CAD may benefit from low-risk guideline directed medical therapies such as HMGCoA reductase inhibitors (ie, “statins”). Recent data suggest that lipid-lowering therapies may even be beneficial for preventing T2MI.⁹

Given the lack of evidence for therapies to treat patients with T2MI or NIMI, clinical judgment remains central to creating an optimal management plan. Clinicians should consider consultation with a cardiologist any time there is ambiguity in whether the diagnosis is T1MI or T2MI. For example, postoperative patients represent a particularly challenging clinical scenario due to the difficulty of assessing ischemic signs and symptoms in the operating room. In this setting, early evaluation by a cardiologist has been shown to improve outcomes.¹⁰

Documentation

Documentation of non-ST elevation MI (NSTEMI) for every case of elevated troponin, rather than using the more specific T1MI, T2MI, or NIMI terminology, can have adverse consequences for health systems. From a coding perspective, the terms STEMI and NSTEMI mean T1MI, and the ICD-10 codes used to identify T1MI patients for value-focused programs frequently include patients with T2MI and NIMI due to imprecise documentation.¹¹ When T2MI and NIMI are imprecisely documented as NSTEMI, health systems and clinicians are held to the T1MI care standards. This can negatively skew the performance of a health system or individual clinician because T2MI and NIMI patients have worse outcomes than T1MI patients.⁴ Inaccurate categorization of patients can lead to inaccurate quality and registry reporting, which may hinder the ability of health systems to monitor and implement quality improvement programs for MI patients. The distinction between T1MI and T2MI in documentation is all the more important now that a new ICD-10 code exists for T2MI (I21.A1), which allows clinicians to more precisely identify these patients, both clinically and administratively, as distinct from T1MI patients.¹² While there is no similarly specific ICD-10 code for NIMI, using the appropriate terminology in documentation should prompt coding personnel to use a code for “other abnormal findings of blood chemistry,” reflecting cardiac biomarker elevation (R79.89), rather than using one of the T1MI codes. Clinicians may not be able to determine the etiology of troponin elevation in the initial phase of a hospitalization, but a definitive diagnosis should be documented in the discharge summary.

From the patient perspective, documentation using STEMI and NSTEMI can mislead clinicians, given that this terminology does not specify the underlying cause (ie, plaque rupture or oxygen supply-demand mismatch), potentially leading to delayed initiation of appropriate therapy. Incorrect documentation, using STEMI/NSTEMI language or incorrectly labeling T2MI and NIMI, may lead patients to believe they have had a heart attack when they had myocardial injury instead. This may lead to unnecessary anxiety and change their interactions with the health system. These patients may be started on unnecessary therapies, have inaccurate preoperative evaluations, and be labeled with a preexisting condition for the rest of their lives.

Opportunities for Quality Improvement

Systems-based quality improvement can help to ensure that patients with NIMI and T2MI are labeled appropriately and receive the proper treatment. Clinical education is the cornerstone of such efforts. Hospital medicine practitioners looking for support in understanding this issue might first partner with cardiology colleagues who may already have training materials available. Billing and coding personnel stand to benefit from greater orientation to this topic considering the complexities and errors in the coding of MI. In an attempt to help nonclinical coding personnel, leaders in the American College of Cardiology have advocated for use of the term “non-MI troponin elevation” (nMITE)¹³ to describe NIMI patients. Finally, we see an important role for EHR-embedded decision support tools to facilitate appropriate documentation and management of patients with elevated troponin. A potential care pathway, for example, could be created in partnership between hospital medicine and cardiology providers to identify which patients would benefit from cardiologist consultation.

Understanding the definitions of T1MI, T2MI, and NIMI will help clinicians to better identify the appropriate clinical care and consultation strategy for patients with elevated cardiac troponin. There are relatively few published quality improvement initiatives to help guide clinicians through these nuanced distinctions, but there is great potential in such approaches to help clinicians provide the highest value care possible.

Disclosures

No authors have any conflict of interest, financial or otherwise, to declare regarding this study.

Funding

Dr. Levy receives funding from National Institutes of Health (NIH) T32 Training Grant 5T32-HL007822.

Elevated serum troponin clearly does not equal myocardial infarction (MI). This was the strong message in the 2018 publication of the Fourth Universal Definition of Myocardial Infarction¹ (4UDMI), the first update to the international consensus document since 2012.

Most clinicians have learned how to accurately diagnose the classic Type 1 MI (T1MI) due to atherosclerotic plaque rupture; however, elevated troponin in the absence of T1MI is increasingly common due to more frequent and less discriminate troponin testing.² Patients with elevated troponin in the absence of T1MI have traditionally created confusion and variability in diagnosis, management, and documentation. Interpretation and management of elevated troponin in the absence of T1MI has become difficult.

In this clinical practice update, we aim to review the updated definition of Type 2 MI (T2MI) and nonischemic myocardial injury (NIMI), since these are the two predominant diagnoses among patients with elevated troponin in the absence of T1MI. We also provide a clinical framework for clinicians to think through elevated serum cardiac troponin levels and identify opportunities for quality improvement around this critical issue.

The presence of an elevated serum troponin level is a critical component in determining the presence of cardiac myocyte injury and possible infarction. Myocardial injury is defined as the presence of serum troponin above the 99th percentile of the upper reference limit (URL), the absolute value of which varies by assay and which applies to traditional and highly sensitive subtypes. Myocardial injury can be confusing to assess, as it can be acute or chronic.

When troponin levels are elevated but stable, this is indicative of chronic (usually nonischemic) myocardial injury, as seen, for example, in patients who have end-stage renal disease. The presence of acute injury requires a change in the troponin value—specifically a rise and/or fall in troponin levels with serial measurements. What constitutes a significant “rise and/or fall” is a matter of some debate and is not precisely defined in the 4UDMI. The percent change in the troponin value over time (relative delta) is listed as part of the criteria for acute injury when the change is greater than or equal to 20%;¹ however, clinicians should be aware that absolute delta in troponin (the change in ng/dL) has better performance characteristics³ in diagnosing acute myocardial injury. Regardless of whether clinicians use relative or absolute changes in the serum troponin level, clinical evaluation of patients with acute injury is critical to establishing whether the injury is ischemic (MI) or nonischemic (NIMI). The presence of at least one of the following is necessary to meet the current criteria for myocardial ischemia according to the fourth universal definition: new ischemic symptoms (eg, chest pain, dyspnea, etc.), new ischemic changes in the patient’s electrocardiogram (eg, new ST segment depression in leads II, III, and aVF), or cardiac imaging changes consistent with ischemic injury (eg, new wall motion abnormality in the inferior wall on echocardiography).

Following diagnosis of MI based on elevated troponin and new symptoms or signs, the cause of MI should then be determined. Type 1 MI remains defined as MI caused by atherosclerotic plaque disruption in a patient with coronary artery disease (CAD). Type 2 MI is not caused by plaque disruption but is due to a mismatch between oxygen supply and demand unrelated to acute atherothrombosis. T2MI is an ischemic myocardial injury traceable to some other illness that leads to inadequate myocyte oxygenation. Causes of T2MI are numerous, can overlap with nonischemic injury, and can include severe anemia, septic shock, rapid atrial fibrillation, and coronary dissection. While CAD may be present in patients with T2MI, it is not a requirement, and an increased demand for, or reduced supply of, myocyte oxygen alone can be sufficient to cause MI.

In the absence of clinical signs or symptoms of cardiac ischemia, clinicians should categorize patients as having a nonischemic myocardial injury. There is significant overlap between causes of T2MI and NIMI, for example, sepsis could cause either T2MI or NIMI. What distinguishes these two entities is whether the signs and symptoms for myocardial ischemia as outlined above are present. If these signs or symptoms are present, the diagnosis is T2MI. If no clinical signs or symptoms of ischemia are present, the diagnosis is NIMI. The assessment of the clinician, using all available clinical information, is pivotal. The characteristics of the three major types of myocardial injury are depicted in the Figure.

Proper distinction between infarction or injury without infarction is central to proper evaluation, treatment, and eventual documentation in patients with elevated troponin levels. In the case of T2MI and NIMI, identifying what underlying illness is causing the troponin elevation is essential for acute management.

Evaluation

Troponin elevation is associated with an elevated risk for major adverse cardiovascular events, regardless of etiology.⁴ While patients with suspected T1MI are most often evaluated by coronary angiography, this may not be necessary for patients with T2MI or NIMI. Developing an evaluation strategy for patients with T2MI or NIMI requires understanding the underlying etiology of myocardial injury. In patients with septic shock for example, there are many potential mechanisms for cardiac myocyte injury, many of which are nonischemic (eg, cytokine-mediated).⁵ Prompt evaluation and treatment of septic shock, therefore, often leads to resolution of cardiac dysfunction, and ischemic evaluation may not be necessary.⁶ In many cases of T2MI or NIMI, waiting for an acute underlying illness to resolve is necessary before deciding whether ischemic evaluation is appropriate. It is important that this decision is deferred but not forgotten though as patients with T2MI or NIMI may benefit from further cardiac evaluation. There are no society recommendations and minimal evidence to guide this evaluation, but clinical trials testing different evaluation strategies are underway.⁷ Until an optimal evidence-based evaluation strategy becomes clear, clinicians should focus on two key principles: first, determine and treat the underlying etiology; second, identify patients with traditional risk factors for CAD and consider further evaluation with either coronary angiography or cardiac imaging. Referral to a cardiologist for assistance with the latter issue, especially for challenging or equivocal cases, is encouraged.

Treatment

While T1MI therapies have a strong evidence base with high rates of appropriate treatment, there are relatively few evidence-based therapies for T2MI and NIMI. The benefits of traditional T1MI therapies should be considered in terms of each therapy’s risk-benefit profile. Among patients with T2MI or NIMI in whom atherosclerotic plaque rupture is unlikely, or in whom bleeding risk is high, antithrombotic agents such as unfractionated heparin and dual antiplatelet therapy represent low value and potentially harmful therapies.⁸ Conversely, patients with multiple risk factors for CAD may benefit from low-risk guideline directed medical therapies such as HMGCoA reductase inhibitors (ie, “statins”). Recent data suggest that lipid-lowering therapies may even be beneficial for preventing T2MI.⁹

Given the lack of evidence for therapies to treat patients with T2MI or NIMI, clinical judgment remains central to creating an optimal management plan. Clinicians should consider consultation with a cardiologist any time there is ambiguity in whether the diagnosis is T1MI or T2MI. For example, postoperative patients represent a particularly challenging clinical scenario due to the difficulty of assessing ischemic signs and symptoms in the operating room. In this setting, early evaluation by a cardiologist has been shown to improve outcomes.¹⁰

Documentation

Documentation of non-ST elevation MI (NSTEMI) for every case of elevated troponin, rather than using the more specific T1MI, T2MI, or NIMI terminology, can have adverse consequences for health systems. From a coding perspective, the terms STEMI and NSTEMI mean T1MI, and the ICD-10 codes used to identify T1MI patients for value-focused programs frequently include patients with T2MI and NIMI due to imprecise documentation.¹¹ When T2MI and NIMI are imprecisely documented as NSTEMI, health systems and clinicians are held to the T1MI care standards. This can negatively skew the performance of a health system or individual clinician because T2MI and NIMI patients have worse outcomes than T1MI patients.⁴ Inaccurate categorization of patients can lead to inaccurate quality and registry reporting, which may hinder the ability of health systems to monitor and implement quality improvement programs for MI patients. The distinction between T1MI and T2MI in documentation is all the more important now that a new ICD-10 code exists for T2MI (I21.A1), which allows clinicians to more precisely identify these patients, both clinically and administratively, as distinct from T1MI patients.¹² While there is no similarly specific ICD-10 code for NIMI, using the appropriate terminology in documentation should prompt coding personnel to use a code for “other abnormal findings of blood chemistry,” reflecting cardiac biomarker elevation (R79.89), rather than using one of the T1MI codes. Clinicians may not be able to determine the etiology of troponin elevation in the initial phase of a hospitalization, but a definitive diagnosis should be documented in the discharge summary.

From the patient perspective, documentation using STEMI and NSTEMI can mislead clinicians, given that this terminology does not specify the underlying cause (ie, plaque rupture or oxygen supply-demand mismatch), potentially leading to delayed initiation of appropriate therapy. Incorrect documentation, using STEMI/NSTEMI language or incorrectly labeling T2MI and NIMI, may lead patients to believe they have had a heart attack when they had myocardial injury instead. This may lead to unnecessary anxiety and change their interactions with the health system. These patients may be started on unnecessary therapies, have inaccurate preoperative evaluations, and be labeled with a preexisting condition for the rest of their lives.

Opportunities for Quality Improvement

Systems-based quality improvement can help to ensure that patients with NIMI and T2MI are labeled appropriately and receive the proper treatment. Clinical education is the cornerstone of such efforts. Hospital medicine practitioners looking for support in understanding this issue might first partner with cardiology colleagues who may already have training materials available. Billing and coding personnel stand to benefit from greater orientation to this topic considering the complexities and errors in the coding of MI. In an attempt to help nonclinical coding personnel, leaders in the American College of Cardiology have advocated for use of the term “non-MI troponin elevation” (nMITE)¹³ to describe NIMI patients. Finally, we see an important role for EHR-embedded decision support tools to facilitate appropriate documentation and management of patients with elevated troponin. A potential care pathway, for example, could be created in partnership between hospital medicine and cardiology providers to identify which patients would benefit from cardiologist consultation.

Understanding the definitions of T1MI, T2MI, and NIMI will help clinicians to better identify the appropriate clinical care and consultation strategy for patients with elevated cardiac troponin. There are relatively few published quality improvement initiatives to help guide clinicians through these nuanced distinctions, but there is great potential in such approaches to help clinicians provide the highest value care possible.

Disclosures

No authors have any conflict of interest, financial or otherwise, to declare regarding this study.

Funding

Dr. Levy receives funding from National Institutes of Health (NIH) T32 Training Grant 5T32-HL007822.

Community-acquired pneumonia (CAP) accounts for more than 1.5 million adult hospitalizations and 100,000 deaths each year in the United States.¹ Antibiotic overuse in the hospital setting is an important contributor to the rise of antibiotic resistance, prompting increased efforts to limit inappropriate antibiotic use in hospitals.² Procalcitonin, a precursor of the hormone calcitonin, is upregulated in bacterial infections and downregulated in viral infections. The US Food and Drug Administration has approved it as a serum biomarker to assist clinicians with decisions about using antibiotics.³

There is no consensus on how to best use procalcitonin in the management of CAP. We provide a practical update that includes a review of recent literature, added secondary analysis, and expert opinion surrounding the use of procalcitonin in the diagnosis and management of CAP in hospitalized adults.

Initial procalcitonin levels do not sufficiently exclude bacterial etiologies of CAP to withhold antibiotic prescription safely. The largest diagnostic accuracy study of procalcitonin in the diagnosis of CAP was a subanalysis of the Etiology of Pneumonia in the Community Study.⁴ A total of 1,735 adults hospitalized with CAP received procalcitonin testing along with systematic pathogen testing. The area under the receiver operating characteristic curve for procalcitonin in discriminating bacterial pathogens from viral pathogens was 0.73 (95% CI, 0.69-0.77). A procalcitonin cut-off of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%-85.7%) sensitivity and 51.6% (95% CI, 46.6%-56.5%) specificity for identification of any bacterial pathogen.

In a secondary analysis of this study, we calculated multilevel likelihood ratios (LRs) for ranges of procalcitonin values to determine the diagnostic accuracy of procalcitonin in distinguishing bacterial from viral etiologies of CAP (Table). Multilevel LRs offer more useful diagnostic information than dichotomizing at specified cut-points.⁵ A procalcitonin result less than 0.1 ng/mL has a negative LR of 0.4 (95% CI, 0.3-0.5), which is not low enough to rule out bacterial CAP effectively when starting with intermediate or high pretest probability. For a low result (<0.1 ng/mL) to be useful in ruling out bacterial CAP, for example having less than a 10% posttest probability of bacterial CAP, the pretest probability would have to be no greater than 22%. Even then, a 10% posttest probability of bacterial CAP may still be too high for clinicians to withhold initial antibiotics. For procalcitonin values between 0.1 ng/mL and 1.0 ng/mL, the probability of bacterial CAP does not change significantly, with an LR of 1.0 (95% CI, 0.8-1.3). Procalcitonin values up to 5 ng/mL reach a modest positive LR of 2.3 (95% CI, 0.8-4.3). Very high values, such as those >10 ng/mL, yield a positive LR of 5.5 (95% CI, 3.2-9.7), are potentially useful in decisions to initiate antibiotics in situations of very low pretest probability of bacterial CAP. For example, a 9% pretest probability of bacterial CAP is likely below many physicians’ threshold for starting antibiotics. A procalcitonin of 12 ng/mL in this patient would increase the posttest probability to 35%, a value that would prompt many physicians to initiate antibiotics.

Overall, there is insufficient evidence to support the use of procalcitonin as a stand-alone test for ruling out bacterial CAP, limiting its use in withholding antibiotics in patients with suspected bacterial CAP.

While initial procalcitonin measurements may not affect the initial antibiotic treatment decision, procalcitonin levels thereafter can guide the duration of therapy. A meta-analysis of procalcitonin-guided treatment in patients with upper or lower respiratory tract infection (LRTI) showed that procalcitonin guidance reduces antibiotic exposure and antibiotic-related adverse effects and improves survival, albeit a small absolute mortality difference of 1.4 percentage points, primarily observed in the intensive care unit setting.⁶ Most patients included in this meta-analysis were diagnosed with LRTI (91%), and CAP was the predominant subtype of LRTI (43%). The main effect of procalcitonin guidance for patients with CAP was earlier discontinuation of antibiotic treatment. Procalcitonin-guided algorithms in these trials discouraged, or strongly discouraged, antibiotics if procalcitonin was <0.25 ng/mL or <0.1 ng/mL, respectively. In addition, serial procalcitonin measurements were used to guide discontinuation of antibiotics if procalcitonin dropped below 0.25 ng/mL, or by 80% to 90% from the peak value. This approach safely shortened the duration of therapy in patients with CAP.

There are several limitations in the interpretation and generalizability of this meta-analysis. There is large heterogeneity across the included clinical trials in design, procalcitonin protocols, clinical setting, and respiratory infection type, including bronchitis, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and CAP. Results were consistent only in one moderate- to high-quality randomized trial specifically studying CAP in the inpatient setting.⁷ Additionally, most of these trials were conducted in Europe. Antibiotic prescribing practices may be different in the US, and prescribing practices on both continents may have changed over the years with greater awareness and appreciation of antibiotic stewardship.

The ProACT trial, the largest randomized, US multicenter trial to evaluate a procalcitonin-based algorithm to assist with antibiotic decision making, included over 1,600 emergency department patients at 14 academic medical centers.⁸ Procalcitonin guidance in this trial did not reduce antibiotic exposure compared with usual care for patients with suspected LRTI. However, its applicability to the practice of hospitalists and the inpatient setting is limited. First, only 48% of the study participants required hospitalization. Second, this study included all LRTIs, with CAP comprising just 20% of all final diagnoses. Third, the average number of antibiotic days during hospitalization for CAP was short in both groups (3.9 days in the procalcitonin group and 4.1 days in the usual care group). This relatively short antibiotic duration makes it difficult for any intervention to decrease antibiotic days meaningfully.

In a prepost controlled intervention study for inpatients at a single US tertiary care hospital, procalcitonin guidance in hospitalized patients safely reduced antibiotic use in LRTI, specifically for the discontinuation of antibiotics.⁹ The greatest benefit of procalcitonin guidance in antibiotic discontinuation was found in patients with AECOPD and patients with an admitting diagnosis of CAP, but with mild illness and a low procalcitonin. Although this prepost study suggested a safe reduction of antibiotic use due to implementation of procalcitonin guidance, the lack of randomization and the absence of a contemporaneous control group are important limitations. Given the mixed findings on the effectiveness of procalcitonin guidance for hospitalized CAP patients in the US, further investigation will be needed with large clinical trials in the inpatient setting for CAP.

There is insufficient evidence to support the use of serum procalcitonin to withhold initial antibiotics in patients with a clinical syndrome consistent with bacterial CAP. However, the literature supports the use of procalcitonin for the early discontinuation of antibiotics for cases in which the probability of bacterial CAP is low, and procalcitonin remains below 0.1 ng/mL (Figure).

Serial measurements of procalcitonin every one to two days may also be used when clinical uncertainty remains regarding the need for antibiotics. Very low or significantly decreasing procalcitonin levels in patients with CAP and no identified bacterial pathogen likely indicate the infection was not bacterial or was bacterial, but has now been adequately treated with antibiotics. For cases of proven bacterial etiology or high clinical suspicion of bacterial CAP, there is insufficient evidence to recommend the early discontinuation of antibiotics based on procalcitonin levels short of the recommended five-day course according to current guidelines.¹⁰ Future clinical trials are needed to determine if procalcitonin guidance can safely decrease the duration of antibiotic therapy for confirmed bacterial CAP to less than five days.

There are discrepancies between the apparent test characteristics of procalcitonin and the recommended antibiotic decisions in many procalcitonin algorithms. For example, algorithms discourage antibiotics when procalcitonin values are 0.1-0.24 ng/mL, and encourage (or even strongly encourage) antibiotic use for higher procalcitonin values of 0.25-1.0 ng/mL. However, the LRs for these ranges are identical and are approximately 1.0 (Table), suggesting that decision-making should be similar across the entire procalcitonin range of 0.1 to 1.0. Future clinical trials should study revised algorithms with different cut-points, including the thresholds found in our secondary analysis of multilevel LRs. Until then, we believe there is insufficient evidence to deviate from current antibiotic decision recommendations at the traditional cut-points.

While procalcitonin is an imperfect biomarker for discriminating bacterial and nonbacterial etiologies of CAP, it may still provide helpful information for the hospitalist in antibiotic decision-making in the same way we apply other commonly used clinical variables such as fever, white blood cell count, band count, and the pattern of infiltrate in chest imaging.

Procalcitonin should be interpreted cautiously in certain populations in which it has not been extensively studied (eg, immunocompromised) or in noninfectious conditions that may elevate procalcitonin, such as major physiologic stress (eg, surgery, trauma, burns) and end-stage renal disease.^12-14 Further investigation is needed to determine the efficacy and safety of procalcitonin-guided antibiotic therapy in these populations.

• Based on currently available data, a low procalcitonin value should not be used as a stand-alone test to withhold antibiotics in a patient with CAP.
• Serum procalcitonin measurements may help guide the early discontinuation of antibiotics for patients who the treating clinician judges the risks of bacterial etiology and clinical deterioration to be low.
• Interpret procalcitonin cautiously in immunocompromised patients, undergoing severe physiologic stress, or have underlying end-stage renal disease.
• Serum procalcitonin serves as an adjunct to, rather than a substitute for, clinical judgment.

Disclosures

Dr Choi, Dr Evans, and Dr Glesby have nothing to disclose. Dr Self reports receiving prior research funding from BRAHMS/Thermo-Fisher and BioMerieux for studies on procalcitonin. Dr Self reports personal fees from Inflammatix, grants from Axis Shield, Rapid Pathogen Screening, and BioMerieux, all outside the submitted work. Dr McCarthy reports receiving research funding from Allergan outside the submitted work. Dr Simon reports receiving consulting fees from Roche Diagnostics.

Community-acquired pneumonia (CAP) accounts for more than 1.5 million adult hospitalizations and 100,000 deaths each year in the United States.¹ Antibiotic overuse in the hospital setting is an important contributor to the rise of antibiotic resistance, prompting increased efforts to limit inappropriate antibiotic use in hospitals.² Procalcitonin, a precursor of the hormone calcitonin, is upregulated in bacterial infections and downregulated in viral infections. The US Food and Drug Administration has approved it as a serum biomarker to assist clinicians with decisions about using antibiotics.³

There is no consensus on how to best use procalcitonin in the management of CAP. We provide a practical update that includes a review of recent literature, added secondary analysis, and expert opinion surrounding the use of procalcitonin in the diagnosis and management of CAP in hospitalized adults.

Initial procalcitonin levels do not sufficiently exclude bacterial etiologies of CAP to withhold antibiotic prescription safely. The largest diagnostic accuracy study of procalcitonin in the diagnosis of CAP was a subanalysis of the Etiology of Pneumonia in the Community Study.⁴ A total of 1,735 adults hospitalized with CAP received procalcitonin testing along with systematic pathogen testing. The area under the receiver operating characteristic curve for procalcitonin in discriminating bacterial pathogens from viral pathogens was 0.73 (95% CI, 0.69-0.77). A procalcitonin cut-off of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%-85.7%) sensitivity and 51.6% (95% CI, 46.6%-56.5%) specificity for identification of any bacterial pathogen.

In a secondary analysis of this study, we calculated multilevel likelihood ratios (LRs) for ranges of procalcitonin values to determine the diagnostic accuracy of procalcitonin in distinguishing bacterial from viral etiologies of CAP (Table). Multilevel LRs offer more useful diagnostic information than dichotomizing at specified cut-points.⁵ A procalcitonin result less than 0.1 ng/mL has a negative LR of 0.4 (95% CI, 0.3-0.5), which is not low enough to rule out bacterial CAP effectively when starting with intermediate or high pretest probability. For a low result (<0.1 ng/mL) to be useful in ruling out bacterial CAP, for example having less than a 10% posttest probability of bacterial CAP, the pretest probability would have to be no greater than 22%. Even then, a 10% posttest probability of bacterial CAP may still be too high for clinicians to withhold initial antibiotics. For procalcitonin values between 0.1 ng/mL and 1.0 ng/mL, the probability of bacterial CAP does not change significantly, with an LR of 1.0 (95% CI, 0.8-1.3). Procalcitonin values up to 5 ng/mL reach a modest positive LR of 2.3 (95% CI, 0.8-4.3). Very high values, such as those >10 ng/mL, yield a positive LR of 5.5 (95% CI, 3.2-9.7), are potentially useful in decisions to initiate antibiotics in situations of very low pretest probability of bacterial CAP. For example, a 9% pretest probability of bacterial CAP is likely below many physicians’ threshold for starting antibiotics. A procalcitonin of 12 ng/mL in this patient would increase the posttest probability to 35%, a value that would prompt many physicians to initiate antibiotics.

Overall, there is insufficient evidence to support the use of procalcitonin as a stand-alone test for ruling out bacterial CAP, limiting its use in withholding antibiotics in patients with suspected bacterial CAP.

While initial procalcitonin measurements may not affect the initial antibiotic treatment decision, procalcitonin levels thereafter can guide the duration of therapy. A meta-analysis of procalcitonin-guided treatment in patients with upper or lower respiratory tract infection (LRTI) showed that procalcitonin guidance reduces antibiotic exposure and antibiotic-related adverse effects and improves survival, albeit a small absolute mortality difference of 1.4 percentage points, primarily observed in the intensive care unit setting.⁶ Most patients included in this meta-analysis were diagnosed with LRTI (91%), and CAP was the predominant subtype of LRTI (43%). The main effect of procalcitonin guidance for patients with CAP was earlier discontinuation of antibiotic treatment. Procalcitonin-guided algorithms in these trials discouraged, or strongly discouraged, antibiotics if procalcitonin was <0.25 ng/mL or <0.1 ng/mL, respectively. In addition, serial procalcitonin measurements were used to guide discontinuation of antibiotics if procalcitonin dropped below 0.25 ng/mL, or by 80% to 90% from the peak value. This approach safely shortened the duration of therapy in patients with CAP.

There are several limitations in the interpretation and generalizability of this meta-analysis. There is large heterogeneity across the included clinical trials in design, procalcitonin protocols, clinical setting, and respiratory infection type, including bronchitis, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and CAP. Results were consistent only in one moderate- to high-quality randomized trial specifically studying CAP in the inpatient setting.⁷ Additionally, most of these trials were conducted in Europe. Antibiotic prescribing practices may be different in the US, and prescribing practices on both continents may have changed over the years with greater awareness and appreciation of antibiotic stewardship.

The ProACT trial, the largest randomized, US multicenter trial to evaluate a procalcitonin-based algorithm to assist with antibiotic decision making, included over 1,600 emergency department patients at 14 academic medical centers.⁸ Procalcitonin guidance in this trial did not reduce antibiotic exposure compared with usual care for patients with suspected LRTI. However, its applicability to the practice of hospitalists and the inpatient setting is limited. First, only 48% of the study participants required hospitalization. Second, this study included all LRTIs, with CAP comprising just 20% of all final diagnoses. Third, the average number of antibiotic days during hospitalization for CAP was short in both groups (3.9 days in the procalcitonin group and 4.1 days in the usual care group). This relatively short antibiotic duration makes it difficult for any intervention to decrease antibiotic days meaningfully.

In a prepost controlled intervention study for inpatients at a single US tertiary care hospital, procalcitonin guidance in hospitalized patients safely reduced antibiotic use in LRTI, specifically for the discontinuation of antibiotics.⁹ The greatest benefit of procalcitonin guidance in antibiotic discontinuation was found in patients with AECOPD and patients with an admitting diagnosis of CAP, but with mild illness and a low procalcitonin. Although this prepost study suggested a safe reduction of antibiotic use due to implementation of procalcitonin guidance, the lack of randomization and the absence of a contemporaneous control group are important limitations. Given the mixed findings on the effectiveness of procalcitonin guidance for hospitalized CAP patients in the US, further investigation will be needed with large clinical trials in the inpatient setting for CAP.

There is insufficient evidence to support the use of serum procalcitonin to withhold initial antibiotics in patients with a clinical syndrome consistent with bacterial CAP. However, the literature supports the use of procalcitonin for the early discontinuation of antibiotics for cases in which the probability of bacterial CAP is low, and procalcitonin remains below 0.1 ng/mL (Figure).

Serial measurements of procalcitonin every one to two days may also be used when clinical uncertainty remains regarding the need for antibiotics. Very low or significantly decreasing procalcitonin levels in patients with CAP and no identified bacterial pathogen likely indicate the infection was not bacterial or was bacterial, but has now been adequately treated with antibiotics. For cases of proven bacterial etiology or high clinical suspicion of bacterial CAP, there is insufficient evidence to recommend the early discontinuation of antibiotics based on procalcitonin levels short of the recommended five-day course according to current guidelines.¹⁰ Future clinical trials are needed to determine if procalcitonin guidance can safely decrease the duration of antibiotic therapy for confirmed bacterial CAP to less than five days.

There are discrepancies between the apparent test characteristics of procalcitonin and the recommended antibiotic decisions in many procalcitonin algorithms. For example, algorithms discourage antibiotics when procalcitonin values are 0.1-0.24 ng/mL, and encourage (or even strongly encourage) antibiotic use for higher procalcitonin values of 0.25-1.0 ng/mL. However, the LRs for these ranges are identical and are approximately 1.0 (Table), suggesting that decision-making should be similar across the entire procalcitonin range of 0.1 to 1.0. Future clinical trials should study revised algorithms with different cut-points, including the thresholds found in our secondary analysis of multilevel LRs. Until then, we believe there is insufficient evidence to deviate from current antibiotic decision recommendations at the traditional cut-points.

While procalcitonin is an imperfect biomarker for discriminating bacterial and nonbacterial etiologies of CAP, it may still provide helpful information for the hospitalist in antibiotic decision-making in the same way we apply other commonly used clinical variables such as fever, white blood cell count, band count, and the pattern of infiltrate in chest imaging.

Procalcitonin should be interpreted cautiously in certain populations in which it has not been extensively studied (eg, immunocompromised) or in noninfectious conditions that may elevate procalcitonin, such as major physiologic stress (eg, surgery, trauma, burns) and end-stage renal disease.^12-14 Further investigation is needed to determine the efficacy and safety of procalcitonin-guided antibiotic therapy in these populations.

• Based on currently available data, a low procalcitonin value should not be used as a stand-alone test to withhold antibiotics in a patient with CAP.
• Serum procalcitonin measurements may help guide the early discontinuation of antibiotics for patients who the treating clinician judges the risks of bacterial etiology and clinical deterioration to be low.
• Interpret procalcitonin cautiously in immunocompromised patients, undergoing severe physiologic stress, or have underlying end-stage renal disease.
• Serum procalcitonin serves as an adjunct to, rather than a substitute for, clinical judgment.

Disclosures

Dr Choi, Dr Evans, and Dr Glesby have nothing to disclose. Dr Self reports receiving prior research funding from BRAHMS/Thermo-Fisher and BioMerieux for studies on procalcitonin. Dr Self reports personal fees from Inflammatix, grants from Axis Shield, Rapid Pathogen Screening, and BioMerieux, all outside the submitted work. Dr McCarthy reports receiving research funding from Allergan outside the submitted work. Dr Simon reports receiving consulting fees from Roche Diagnostics.

Community-acquired pneumonia (CAP) accounts for more than 1.5 million adult hospitalizations and 100,000 deaths each year in the United States.¹ Antibiotic overuse in the hospital setting is an important contributor to the rise of antibiotic resistance, prompting increased efforts to limit inappropriate antibiotic use in hospitals.² Procalcitonin, a precursor of the hormone calcitonin, is upregulated in bacterial infections and downregulated in viral infections. The US Food and Drug Administration has approved it as a serum biomarker to assist clinicians with decisions about using antibiotics.³

There is no consensus on how to best use procalcitonin in the management of CAP. We provide a practical update that includes a review of recent literature, added secondary analysis, and expert opinion surrounding the use of procalcitonin in the diagnosis and management of CAP in hospitalized adults.

Initial procalcitonin levels do not sufficiently exclude bacterial etiologies of CAP to withhold antibiotic prescription safely. The largest diagnostic accuracy study of procalcitonin in the diagnosis of CAP was a subanalysis of the Etiology of Pneumonia in the Community Study.⁴ A total of 1,735 adults hospitalized with CAP received procalcitonin testing along with systematic pathogen testing. The area under the receiver operating characteristic curve for procalcitonin in discriminating bacterial pathogens from viral pathogens was 0.73 (95% CI, 0.69-0.77). A procalcitonin cut-off of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%-85.7%) sensitivity and 51.6% (95% CI, 46.6%-56.5%) specificity for identification of any bacterial pathogen.

In a secondary analysis of this study, we calculated multilevel likelihood ratios (LRs) for ranges of procalcitonin values to determine the diagnostic accuracy of procalcitonin in distinguishing bacterial from viral etiologies of CAP (Table). Multilevel LRs offer more useful diagnostic information than dichotomizing at specified cut-points.⁵ A procalcitonin result less than 0.1 ng/mL has a negative LR of 0.4 (95% CI, 0.3-0.5), which is not low enough to rule out bacterial CAP effectively when starting with intermediate or high pretest probability. For a low result (<0.1 ng/mL) to be useful in ruling out bacterial CAP, for example having less than a 10% posttest probability of bacterial CAP, the pretest probability would have to be no greater than 22%. Even then, a 10% posttest probability of bacterial CAP may still be too high for clinicians to withhold initial antibiotics. For procalcitonin values between 0.1 ng/mL and 1.0 ng/mL, the probability of bacterial CAP does not change significantly, with an LR of 1.0 (95% CI, 0.8-1.3). Procalcitonin values up to 5 ng/mL reach a modest positive LR of 2.3 (95% CI, 0.8-4.3). Very high values, such as those >10 ng/mL, yield a positive LR of 5.5 (95% CI, 3.2-9.7), are potentially useful in decisions to initiate antibiotics in situations of very low pretest probability of bacterial CAP. For example, a 9% pretest probability of bacterial CAP is likely below many physicians’ threshold for starting antibiotics. A procalcitonin of 12 ng/mL in this patient would increase the posttest probability to 35%, a value that would prompt many physicians to initiate antibiotics.

Overall, there is insufficient evidence to support the use of procalcitonin as a stand-alone test for ruling out bacterial CAP, limiting its use in withholding antibiotics in patients with suspected bacterial CAP.

While initial procalcitonin measurements may not affect the initial antibiotic treatment decision, procalcitonin levels thereafter can guide the duration of therapy. A meta-analysis of procalcitonin-guided treatment in patients with upper or lower respiratory tract infection (LRTI) showed that procalcitonin guidance reduces antibiotic exposure and antibiotic-related adverse effects and improves survival, albeit a small absolute mortality difference of 1.4 percentage points, primarily observed in the intensive care unit setting.⁶ Most patients included in this meta-analysis were diagnosed with LRTI (91%), and CAP was the predominant subtype of LRTI (43%). The main effect of procalcitonin guidance for patients with CAP was earlier discontinuation of antibiotic treatment. Procalcitonin-guided algorithms in these trials discouraged, or strongly discouraged, antibiotics if procalcitonin was <0.25 ng/mL or <0.1 ng/mL, respectively. In addition, serial procalcitonin measurements were used to guide discontinuation of antibiotics if procalcitonin dropped below 0.25 ng/mL, or by 80% to 90% from the peak value. This approach safely shortened the duration of therapy in patients with CAP.

There are several limitations in the interpretation and generalizability of this meta-analysis. There is large heterogeneity across the included clinical trials in design, procalcitonin protocols, clinical setting, and respiratory infection type, including bronchitis, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and CAP. Results were consistent only in one moderate- to high-quality randomized trial specifically studying CAP in the inpatient setting.⁷ Additionally, most of these trials were conducted in Europe. Antibiotic prescribing practices may be different in the US, and prescribing practices on both continents may have changed over the years with greater awareness and appreciation of antibiotic stewardship.

The ProACT trial, the largest randomized, US multicenter trial to evaluate a procalcitonin-based algorithm to assist with antibiotic decision making, included over 1,600 emergency department patients at 14 academic medical centers.⁸ Procalcitonin guidance in this trial did not reduce antibiotic exposure compared with usual care for patients with suspected LRTI. However, its applicability to the practice of hospitalists and the inpatient setting is limited. First, only 48% of the study participants required hospitalization. Second, this study included all LRTIs, with CAP comprising just 20% of all final diagnoses. Third, the average number of antibiotic days during hospitalization for CAP was short in both groups (3.9 days in the procalcitonin group and 4.1 days in the usual care group). This relatively short antibiotic duration makes it difficult for any intervention to decrease antibiotic days meaningfully.

In a prepost controlled intervention study for inpatients at a single US tertiary care hospital, procalcitonin guidance in hospitalized patients safely reduced antibiotic use in LRTI, specifically for the discontinuation of antibiotics.⁹ The greatest benefit of procalcitonin guidance in antibiotic discontinuation was found in patients with AECOPD and patients with an admitting diagnosis of CAP, but with mild illness and a low procalcitonin. Although this prepost study suggested a safe reduction of antibiotic use due to implementation of procalcitonin guidance, the lack of randomization and the absence of a contemporaneous control group are important limitations. Given the mixed findings on the effectiveness of procalcitonin guidance for hospitalized CAP patients in the US, further investigation will be needed with large clinical trials in the inpatient setting for CAP.

There is insufficient evidence to support the use of serum procalcitonin to withhold initial antibiotics in patients with a clinical syndrome consistent with bacterial CAP. However, the literature supports the use of procalcitonin for the early discontinuation of antibiotics for cases in which the probability of bacterial CAP is low, and procalcitonin remains below 0.1 ng/mL (Figure).

Serial measurements of procalcitonin every one to two days may also be used when clinical uncertainty remains regarding the need for antibiotics. Very low or significantly decreasing procalcitonin levels in patients with CAP and no identified bacterial pathogen likely indicate the infection was not bacterial or was bacterial, but has now been adequately treated with antibiotics. For cases of proven bacterial etiology or high clinical suspicion of bacterial CAP, there is insufficient evidence to recommend the early discontinuation of antibiotics based on procalcitonin levels short of the recommended five-day course according to current guidelines.¹⁰ Future clinical trials are needed to determine if procalcitonin guidance can safely decrease the duration of antibiotic therapy for confirmed bacterial CAP to less than five days.

There are discrepancies between the apparent test characteristics of procalcitonin and the recommended antibiotic decisions in many procalcitonin algorithms. For example, algorithms discourage antibiotics when procalcitonin values are 0.1-0.24 ng/mL, and encourage (or even strongly encourage) antibiotic use for higher procalcitonin values of 0.25-1.0 ng/mL. However, the LRs for these ranges are identical and are approximately 1.0 (Table), suggesting that decision-making should be similar across the entire procalcitonin range of 0.1 to 1.0. Future clinical trials should study revised algorithms with different cut-points, including the thresholds found in our secondary analysis of multilevel LRs. Until then, we believe there is insufficient evidence to deviate from current antibiotic decision recommendations at the traditional cut-points.

While procalcitonin is an imperfect biomarker for discriminating bacterial and nonbacterial etiologies of CAP, it may still provide helpful information for the hospitalist in antibiotic decision-making in the same way we apply other commonly used clinical variables such as fever, white blood cell count, band count, and the pattern of infiltrate in chest imaging.

Procalcitonin should be interpreted cautiously in certain populations in which it has not been extensively studied (eg, immunocompromised) or in noninfectious conditions that may elevate procalcitonin, such as major physiologic stress (eg, surgery, trauma, burns) and end-stage renal disease.^12-14 Further investigation is needed to determine the efficacy and safety of procalcitonin-guided antibiotic therapy in these populations.

• Based on currently available data, a low procalcitonin value should not be used as a stand-alone test to withhold antibiotics in a patient with CAP.
• Serum procalcitonin measurements may help guide the early discontinuation of antibiotics for patients who the treating clinician judges the risks of bacterial etiology and clinical deterioration to be low.
• Interpret procalcitonin cautiously in immunocompromised patients, undergoing severe physiologic stress, or have underlying end-stage renal disease.
• Serum procalcitonin serves as an adjunct to, rather than a substitute for, clinical judgment.

Disclosures

Dr Choi, Dr Evans, and Dr Glesby have nothing to disclose. Dr Self reports receiving prior research funding from BRAHMS/Thermo-Fisher and BioMerieux for studies on procalcitonin. Dr Self reports personal fees from Inflammatix, grants from Axis Shield, Rapid Pathogen Screening, and BioMerieux, all outside the submitted work. Dr McCarthy reports receiving research funding from Allergan outside the submitted work. Dr Simon reports receiving consulting fees from Roche Diagnostics.