CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.

CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.

CHICAGO – While tyrosine kinase inhibitors (TKIs) have long dominated treatment approaches for EGFR-driven advanced non-small cell lung cancer, a few newer antibodies are showing early promise as potential new strategies to use after progression, recent reports show.

Both JNJ-372, an EGFR and MET bispecific antibody, and U3-1402, a HER3-directed antibody-drug conjugate (ADC), demonstrated manageable safety profiles and preliminary antitumor activity in phase 1 study results presented here at the annual meeting of the American Society of Clinical Oncology.

“There is definitely a role to play for antibodies in the TKI world,” said Jessica Ruth Bauman, MD, of Fox Chase Cancer Center, Philadelphia, Pa., a discussant on both abstracts.

These two antibodies harness new mechanisms of action that are not specific to a resistance mechanism, which may lead to broad applicability, according to Dr. Bauman.

“Mechanisms of acquired resistance have been the Achilles heel of EGFR TKI treatment,” she said.

The JNJ-372 bispecific antibody has preclinical data consistent with several proposed mechanisms of action, including inhibition of EGFR and cMet signaling, receptor degradation, and antibody-dependent cellular cytotoxicity, said investigator Eric B. Haura, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.

In the phase 1 study, which included patients with diverse EGFR mutations, 32 out of 108 patients (30%) had a best response of partial response (PR) after treatment with JNJ-372, Dr. Haura reported in an oral abstract presentation.

Responses were seen in patients with mutations that represent areas of high unmet need, including those with EGFR C797S-mediated or cMet-mediated resistance to the third-generation TKI osimertinib, and those with TKI-naïve EGFR exon 20 insertions, he emphasized in his presentation.

The safety profile was “manageable” and consistent with EGFR inhibition, he said, with a low (9%) rate of grade 3 or greater toxicities and frequent infusion-related reactions, mostly after the first dose.

Enrollment of patients with high unmet need is ongoing, according to Dr. Haura.

U3-1402, the antibody-drug conjugate that may have a place in the TKI world, consists of a fully human HER3-targeted antibody linked to a topoisomerase I inhibitor payload.

“Targeting HER3 with U3-1402 may be a practical approach to treat EGFR-mutant NSCLC with diverse mechanisms of resistance to EGFR TKIs,” said investigator Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, Mass.

That’s because mechanisms of resistance to TKIs in EGFR-mutant NSCLC are turning out to be so diverse, that trying to combat each individual resistance mechanism is likely “impractical,” Dr. Jänne said.

Targeting HER3, the perhaps lesser-known of the four members of the EGFR tyrosine kinase family, may address multiple resistance mechanisms, and 57% to 67% of EGFR-mutant NSCLCs have at least some level of HER3 expression, according to the presenter.

In the phase 1 study data reported at the meeting, the response rate following U3-1402 treatment was about 31%, or 5 out of 16 patients, including 4 confirmed partial responses. Most treatment-emergent adverse events were grade 1 or 2, and only one patient discontinued due to an adverse event, according to Dr. Jänne, who said the study is ongoing.

Taken together, findings for U3-1402 and JNJ-372 show that there may be room for other approaches beyond TKIs to address the need for new therapies to overcome resistance, Dr. Bauman said in her commentary on these studies.

“Additional research will enable us to determine who will benefit from these compounds, what biomarkers are predictive, and novel combinations to consider,” she added.

Dr. Bauman reported a consulting or advisory role with Pfizer. Dr. Haura provided disclosures related to Bristol-Myers Squibb; Janssen Oncology, Boehringer Ingelheim, FORMA Therapeutics, Ignyta, Janssen, Lilly, and Ventana, plus a patent pending on technology related to kinase inhibitor sensitivity biomarkers. Dr. Jänne reported disclosures related to Gatekeeper Pharmaceuticals, Loxo, Araxes Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, and others.

SOURCE: Haura EB, et al. ASCO 2019. Abstract 9009, Jänne PA, et al. ASCO 2019. Abstract 9010.

CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.

Jennifer Smith/MDedge News

In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.

“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.

Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.

The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.

The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.

Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.

Dosing and toxicity

During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m² on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m² was deemed the recommended phase 2 dose.

The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).

The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).

Response and survival

There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).

The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).

During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).

During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).

Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.

Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.

The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.

“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”

AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.

jensmith@mdedge.com

SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.

CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.

Jennifer Smith/MDedge News

In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.

“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.

Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.

The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.

The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.

Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.

Dosing and toxicity

During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m² on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m² was deemed the recommended phase 2 dose.

The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).

The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).

Response and survival

There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).

The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).

During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).

During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).

Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.

Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.

The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.

“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”

AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.

jensmith@mdedge.com

SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.

CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.

Jennifer Smith/MDedge News

In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.

“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.

Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.

The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.

The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.

Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.

Dosing and toxicity

During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m² on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m² was deemed the recommended phase 2 dose.

The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).

The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).

Response and survival

There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).

The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).

During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).

During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).

Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.

Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.

The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.

“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”

AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.

jensmith@mdedge.com

SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.

When I entered the examination room, I saw his alma mater’s logo on his wristwatch. He was a retired physician with a new diagnosis of leukemia who drove to see me, even though he lived closer to his beloved medical school where he had practiced his entire career.

As is frequently the case, he came to see me because he could not get the appointment he wanted in his university’s clinic for another 6 months. He called us on Friday, and 3 days later, he and I were meeting. He is still an ardent supporter of his institution, but I am now his hematologist.

As it turned out, his leukemia was asymptomatic, indolent, and required no treatment. He could have waited 6 months to be seen. But, no; he couldn’t.

This story repeats itself over and over again. A sick patient calls to be seen and is told there is no availability for weeks or months. I do not understand how health care facilities, my own included, find this acceptable.

My father was very proud of his policy to see every patient in his waiting room no matter how long his office needed to stay open. He felt that access was of primary importance to his patients and to his practice. If he didn’t see them, somebody else would. Those of us working in large academic centers do not always feel the financial consequences of patients lost because of poor service.

Luckily, I work in a large cancer center that values access as much as a small practice would. When a patient calls us with a hematologic problem, we see them in less than 7 days, unless the patient prefers a different time frame. We monitor the time it takes to see patients and proactively assess upcoming appointments to ensure insurance coverage and the availability of records. If an obstruction is identified, the case is escalated to administrative leadership to be addressed and resolved. We are very proud of this work.

However, our focus on access does not end there. Once seen, we expedite patient evaluation by assessing workflows to obtain all necessary testing as quickly as possible. By doing so, we accelerate the time it takes from diagnosis to the time we start treating (time to treat). We have always tried to reduce time to treat for acute leukemia and we have applied those lessons to patients with lymphoma and solid tumors, resulting in a 33% improvement over the last 5 years.

We not only lessen the anxiety that comes with a scary diagnosis, emerging data indicate outcomes are improved with faster treatment, too (PLoS One. 2019 Mar 1;14(3):e0213209. doi: 10.1371/journal.pone.0213209).

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at kalaycm@ccf.org.

When I entered the examination room, I saw his alma mater’s logo on his wristwatch. He was a retired physician with a new diagnosis of leukemia who drove to see me, even though he lived closer to his beloved medical school where he had practiced his entire career.

As is frequently the case, he came to see me because he could not get the appointment he wanted in his university’s clinic for another 6 months. He called us on Friday, and 3 days later, he and I were meeting. He is still an ardent supporter of his institution, but I am now his hematologist.

As it turned out, his leukemia was asymptomatic, indolent, and required no treatment. He could have waited 6 months to be seen. But, no; he couldn’t.

This story repeats itself over and over again. A sick patient calls to be seen and is told there is no availability for weeks or months. I do not understand how health care facilities, my own included, find this acceptable.

My father was very proud of his policy to see every patient in his waiting room no matter how long his office needed to stay open. He felt that access was of primary importance to his patients and to his practice. If he didn’t see them, somebody else would. Those of us working in large academic centers do not always feel the financial consequences of patients lost because of poor service.

Luckily, I work in a large cancer center that values access as much as a small practice would. When a patient calls us with a hematologic problem, we see them in less than 7 days, unless the patient prefers a different time frame. We monitor the time it takes to see patients and proactively assess upcoming appointments to ensure insurance coverage and the availability of records. If an obstruction is identified, the case is escalated to administrative leadership to be addressed and resolved. We are very proud of this work.

However, our focus on access does not end there. Once seen, we expedite patient evaluation by assessing workflows to obtain all necessary testing as quickly as possible. By doing so, we accelerate the time it takes from diagnosis to the time we start treating (time to treat). We have always tried to reduce time to treat for acute leukemia and we have applied those lessons to patients with lymphoma and solid tumors, resulting in a 33% improvement over the last 5 years.

We not only lessen the anxiety that comes with a scary diagnosis, emerging data indicate outcomes are improved with faster treatment, too (PLoS One. 2019 Mar 1;14(3):e0213209. doi: 10.1371/journal.pone.0213209).

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at kalaycm@ccf.org.

When I entered the examination room, I saw his alma mater’s logo on his wristwatch. He was a retired physician with a new diagnosis of leukemia who drove to see me, even though he lived closer to his beloved medical school where he had practiced his entire career.

As is frequently the case, he came to see me because he could not get the appointment he wanted in his university’s clinic for another 6 months. He called us on Friday, and 3 days later, he and I were meeting. He is still an ardent supporter of his institution, but I am now his hematologist.

As it turned out, his leukemia was asymptomatic, indolent, and required no treatment. He could have waited 6 months to be seen. But, no; he couldn’t.

This story repeats itself over and over again. A sick patient calls to be seen and is told there is no availability for weeks or months. I do not understand how health care facilities, my own included, find this acceptable.

My father was very proud of his policy to see every patient in his waiting room no matter how long his office needed to stay open. He felt that access was of primary importance to his patients and to his practice. If he didn’t see them, somebody else would. Those of us working in large academic centers do not always feel the financial consequences of patients lost because of poor service.

Luckily, I work in a large cancer center that values access as much as a small practice would. When a patient calls us with a hematologic problem, we see them in less than 7 days, unless the patient prefers a different time frame. We monitor the time it takes to see patients and proactively assess upcoming appointments to ensure insurance coverage and the availability of records. If an obstruction is identified, the case is escalated to administrative leadership to be addressed and resolved. We are very proud of this work.

However, our focus on access does not end there. Once seen, we expedite patient evaluation by assessing workflows to obtain all necessary testing as quickly as possible. By doing so, we accelerate the time it takes from diagnosis to the time we start treating (time to treat). We have always tried to reduce time to treat for acute leukemia and we have applied those lessons to patients with lymphoma and solid tumors, resulting in a 33% improvement over the last 5 years.

We not only lessen the anxiety that comes with a scary diagnosis, emerging data indicate outcomes are improved with faster treatment, too (PLoS One. 2019 Mar 1;14(3):e0213209. doi: 10.1371/journal.pone.0213209).

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at kalaycm@ccf.org.

“If it is true that the full humanity of women is not our culture, then we can and must make it our culture.”
—Chimamanda Ngozi Adichie

A young boy is on the way home from soccer when a driver hits his car head-on. His father dies immediately, but the boy survives. The boy is transported to the hospital and immediately rushed into the OR. The surgeon takes one look at him and says, “I can’t operate on this patient. He’s my son!” The riddle asks: If the father is dead, who is the surgeon?

Struggling to realize that the surgeon is a mom highlights the depth of gender bias in medicine. Gender bias leads to inequities which are magnified when compounded with differences in race, ethnicity, sexual orientation, gender identity and/or socioeconomic status. The recent National Academies report described the toll of gender inequities, including sexual harassment, and their impact on women in medicine.¹ But like this riddle, the focus was directed towards those at the top of the hierarchy: physicians. It is undeniable that women physicians suffer the effects of inequities, but why exclude other women in healthcare? For example, over 90% of nurses are female, yet male nurses make higher salaries with lower degrees.² If we only focus on physicians, we risk ignoring a problem faced by the entirety of our workforce.

Healthcare is a team sport. The practice of hospital medicine is a prime example of how each team member brings critical value. One would never be able to run an effective code without excellent nursing or successfully intubate a patient without a skilled respiratory therapist. Yet, when it comes to conversations about gender bias and sexual harassment, we rarely work together. The work of equity in healthcare must therefore become more like a lattice than a ladder, with many of us advocating for or with one another.

As hospital medicine has grown, hospitalists have become genuine agents of change. Therefore, this change too, must begin with hospitalists. As leaders in healthcare, we must advocate for equity for all, from the lab technician to the CEO. We must engage and respond when direct care workers (often minorities), face gender or racial bias. In short, if we see something, we must say something.

To create a culture of inclusivity and intersectionality in healthcare, we suggest the following:

• Unite healthcare workers across fields. View your fellow healthcare worker as a team member, not as a subordinate or ancillary staff. Ask them what their experiences regarding inequity have been. See things from their perspective.
• Be a champion for those affected by harassment and inequity. Offer direct support to anyone affected by harassment or inequity. Accompany them to human resources or use your influence to advocate for gender-based salary audits.
• Raise awareness and knowledge. Know the resources in your institution and share them with others. Encourage teams to discuss the impact of microaggressions and implicit bias together as opposed to in role-specific groups. Use communication to lend allyship and support. If you see microaggressions based on gender or race, inquire by asking “I’m curious...why would you say that?” or share the impact a statement has on you by noting “The comment doesn’t just affect one person, it affects all of us.”

People create culture. Meaningful cultural change must be inclusive and intersectional. Historically, movements focused on equity have failed to be inclusive, leading to certain groups feeling marginalized. The time has come to affect change in healthcare across all differences. Whether in the role of physician, nurse, advanced practice provider, or paramedical staff, it’s time to stand together and say: “time is up.”

Disclosures

Dr Kass and Dr. Acholonu are founding members of TIME’S UP Healthcare

“If it is true that the full humanity of women is not our culture, then we can and must make it our culture.”
—Chimamanda Ngozi Adichie

A young boy is on the way home from soccer when a driver hits his car head-on. His father dies immediately, but the boy survives. The boy is transported to the hospital and immediately rushed into the OR. The surgeon takes one look at him and says, “I can’t operate on this patient. He’s my son!” The riddle asks: If the father is dead, who is the surgeon?

Struggling to realize that the surgeon is a mom highlights the depth of gender bias in medicine. Gender bias leads to inequities which are magnified when compounded with differences in race, ethnicity, sexual orientation, gender identity and/or socioeconomic status. The recent National Academies report described the toll of gender inequities, including sexual harassment, and their impact on women in medicine.¹ But like this riddle, the focus was directed towards those at the top of the hierarchy: physicians. It is undeniable that women physicians suffer the effects of inequities, but why exclude other women in healthcare? For example, over 90% of nurses are female, yet male nurses make higher salaries with lower degrees.² If we only focus on physicians, we risk ignoring a problem faced by the entirety of our workforce.

Healthcare is a team sport. The practice of hospital medicine is a prime example of how each team member brings critical value. One would never be able to run an effective code without excellent nursing or successfully intubate a patient without a skilled respiratory therapist. Yet, when it comes to conversations about gender bias and sexual harassment, we rarely work together. The work of equity in healthcare must therefore become more like a lattice than a ladder, with many of us advocating for or with one another.

As hospital medicine has grown, hospitalists have become genuine agents of change. Therefore, this change too, must begin with hospitalists. As leaders in healthcare, we must advocate for equity for all, from the lab technician to the CEO. We must engage and respond when direct care workers (often minorities), face gender or racial bias. In short, if we see something, we must say something.

To create a culture of inclusivity and intersectionality in healthcare, we suggest the following:

• Unite healthcare workers across fields. View your fellow healthcare worker as a team member, not as a subordinate or ancillary staff. Ask them what their experiences regarding inequity have been. See things from their perspective.
• Be a champion for those affected by harassment and inequity. Offer direct support to anyone affected by harassment or inequity. Accompany them to human resources or use your influence to advocate for gender-based salary audits.
• Raise awareness and knowledge. Know the resources in your institution and share them with others. Encourage teams to discuss the impact of microaggressions and implicit bias together as opposed to in role-specific groups. Use communication to lend allyship and support. If you see microaggressions based on gender or race, inquire by asking “I’m curious...why would you say that?” or share the impact a statement has on you by noting “The comment doesn’t just affect one person, it affects all of us.”

People create culture. Meaningful cultural change must be inclusive and intersectional. Historically, movements focused on equity have failed to be inclusive, leading to certain groups feeling marginalized. The time has come to affect change in healthcare across all differences. Whether in the role of physician, nurse, advanced practice provider, or paramedical staff, it’s time to stand together and say: “time is up.”

Disclosures

Dr Kass and Dr. Acholonu are founding members of TIME’S UP Healthcare

“If it is true that the full humanity of women is not our culture, then we can and must make it our culture.”
—Chimamanda Ngozi Adichie

A young boy is on the way home from soccer when a driver hits his car head-on. His father dies immediately, but the boy survives. The boy is transported to the hospital and immediately rushed into the OR. The surgeon takes one look at him and says, “I can’t operate on this patient. He’s my son!” The riddle asks: If the father is dead, who is the surgeon?

Struggling to realize that the surgeon is a mom highlights the depth of gender bias in medicine. Gender bias leads to inequities which are magnified when compounded with differences in race, ethnicity, sexual orientation, gender identity and/or socioeconomic status. The recent National Academies report described the toll of gender inequities, including sexual harassment, and their impact on women in medicine.¹ But like this riddle, the focus was directed towards those at the top of the hierarchy: physicians. It is undeniable that women physicians suffer the effects of inequities, but why exclude other women in healthcare? For example, over 90% of nurses are female, yet male nurses make higher salaries with lower degrees.² If we only focus on physicians, we risk ignoring a problem faced by the entirety of our workforce.

Healthcare is a team sport. The practice of hospital medicine is a prime example of how each team member brings critical value. One would never be able to run an effective code without excellent nursing or successfully intubate a patient without a skilled respiratory therapist. Yet, when it comes to conversations about gender bias and sexual harassment, we rarely work together. The work of equity in healthcare must therefore become more like a lattice than a ladder, with many of us advocating for or with one another.

As hospital medicine has grown, hospitalists have become genuine agents of change. Therefore, this change too, must begin with hospitalists. As leaders in healthcare, we must advocate for equity for all, from the lab technician to the CEO. We must engage and respond when direct care workers (often minorities), face gender or racial bias. In short, if we see something, we must say something.

To create a culture of inclusivity and intersectionality in healthcare, we suggest the following:

• Unite healthcare workers across fields. View your fellow healthcare worker as a team member, not as a subordinate or ancillary staff. Ask them what their experiences regarding inequity have been. See things from their perspective.
• Be a champion for those affected by harassment and inequity. Offer direct support to anyone affected by harassment or inequity. Accompany them to human resources or use your influence to advocate for gender-based salary audits.
• Raise awareness and knowledge. Know the resources in your institution and share them with others. Encourage teams to discuss the impact of microaggressions and implicit bias together as opposed to in role-specific groups. Use communication to lend allyship and support. If you see microaggressions based on gender or race, inquire by asking “I’m curious...why would you say that?” or share the impact a statement has on you by noting “The comment doesn’t just affect one person, it affects all of us.”

People create culture. Meaningful cultural change must be inclusive and intersectional. Historically, movements focused on equity have failed to be inclusive, leading to certain groups feeling marginalized. The time has come to affect change in healthcare across all differences. Whether in the role of physician, nurse, advanced practice provider, or paramedical staff, it’s time to stand together and say: “time is up.”

Disclosures

Dr Kass and Dr. Acholonu are founding members of TIME’S UP Healthcare

We appreciate the comments and interest of Al-Sharefi and colleagues who highlight the use of glucose-only infusion in the management of hyperkalemia.¹ The incidence of hypoglycemia following hyperkalemia treatment with insulin/dextrose is high and measures to reduce this should be pursued.² However, evidence of the efficacy of glucose-only infusions on lowering potassium in heterogeneous inpatient populations is lacking. The small study by Chothia et al demonstrated potassium lowering efficacy in ten clinically stable patients without diabetes receiving chronic hemodialysis.³ In contrast, multiple observational studies consistently show a clinically significant effect of insulin/dextrose on potassium lowering across different populations.⁴

Importantly, inpatient hyperglycemia is associated with increased morbidity and mortality and occurs in those with preexisting diabetes and also those without, due to stress hyperglycemia from acute illness, medication or nutrition support.⁵ Determining intact insulin sensitivity during acute illness is not straightforward and deciding on the appropriateness of glucose-only hyperkalemia treatment compared with insulin/dextrose would be challenging. With the rising prevalence of diabetes in the inpatient setting (>30% in our study), the number of eligible individuals for glucose-only treatment would be small and does not justify the use of two separate hyperkalemia treatment protocols.

Given the potential life-threatening consequences of hyperkalemia, rapid potassium lowering is a priority. For glucose-only infusions to be applied, there needs to be more convincing evidence across more representative inpatient populations to ensure efficacy.

Disclosures

The authors have nothing to disclose.

We appreciate the comments and interest of Al-Sharefi and colleagues who highlight the use of glucose-only infusion in the management of hyperkalemia.¹ The incidence of hypoglycemia following hyperkalemia treatment with insulin/dextrose is high and measures to reduce this should be pursued.² However, evidence of the efficacy of glucose-only infusions on lowering potassium in heterogeneous inpatient populations is lacking. The small study by Chothia et al demonstrated potassium lowering efficacy in ten clinically stable patients without diabetes receiving chronic hemodialysis.³ In contrast, multiple observational studies consistently show a clinically significant effect of insulin/dextrose on potassium lowering across different populations.⁴

Importantly, inpatient hyperglycemia is associated with increased morbidity and mortality and occurs in those with preexisting diabetes and also those without, due to stress hyperglycemia from acute illness, medication or nutrition support.⁵ Determining intact insulin sensitivity during acute illness is not straightforward and deciding on the appropriateness of glucose-only hyperkalemia treatment compared with insulin/dextrose would be challenging. With the rising prevalence of diabetes in the inpatient setting (>30% in our study), the number of eligible individuals for glucose-only treatment would be small and does not justify the use of two separate hyperkalemia treatment protocols.

Given the potential life-threatening consequences of hyperkalemia, rapid potassium lowering is a priority. For glucose-only infusions to be applied, there needs to be more convincing evidence across more representative inpatient populations to ensure efficacy.

Disclosures

The authors have nothing to disclose.

We appreciate the comments and interest of Al-Sharefi and colleagues who highlight the use of glucose-only infusion in the management of hyperkalemia.¹ The incidence of hypoglycemia following hyperkalemia treatment with insulin/dextrose is high and measures to reduce this should be pursued.² However, evidence of the efficacy of glucose-only infusions on lowering potassium in heterogeneous inpatient populations is lacking. The small study by Chothia et al demonstrated potassium lowering efficacy in ten clinically stable patients without diabetes receiving chronic hemodialysis.³ In contrast, multiple observational studies consistently show a clinically significant effect of insulin/dextrose on potassium lowering across different populations.⁴

Importantly, inpatient hyperglycemia is associated with increased morbidity and mortality and occurs in those with preexisting diabetes and also those without, due to stress hyperglycemia from acute illness, medication or nutrition support.⁵ Determining intact insulin sensitivity during acute illness is not straightforward and deciding on the appropriateness of glucose-only hyperkalemia treatment compared with insulin/dextrose would be challenging. With the rising prevalence of diabetes in the inpatient setting (>30% in our study), the number of eligible individuals for glucose-only treatment would be small and does not justify the use of two separate hyperkalemia treatment protocols.

Given the potential life-threatening consequences of hyperkalemia, rapid potassium lowering is a priority. For glucose-only infusions to be applied, there needs to be more convincing evidence across more representative inpatient populations to ensure efficacy.

Disclosures

The authors have nothing to disclose.

Boughton et al.¹ reported a high incidence of hypoglycemia resulting from glucose-with-insulin (GwI) infusion used to treat acute hyperkalemia. This has been reported by other investigators—particularly in subjects without preexisting diabetes² and resonates with the experiences of clinicians practicing in Internal Medicine or Diabetes.

The authors suggested that patients at risk of hypoglycemia be identified and offered a regimen containing less insulin. However, for subjects without preexisting diagnosis and not at high risk of diabetes, we question the physiological logic and the safety basis for administering insulin.

Infusion of glucose only (GO) to subjects with intact pancreatic function and insulin sensitivity stimulates endogenous insulin secretion in a dose-dependent manner, resulting in a reduction in extracellular fluid potassium with no risk of hypoglycemia.^3,4

It is unclear why GwI historically entered mainstream practice rather than GO, but the rationale may have been based on the potential risks of paradoxical hyperglycemia-mediated hyperkalemia (HMK) being induced by GO. In practice, HMK was only observed in subjects with diabetes.⁵

As there is an ongoing need to reduce the impact of iatrogenic hypoglycemia, revisiting of the prematurely abandoned GO regimen in hyperkalemia management is warranted. Such approach may offer a safe and physiological alternative to GwI in nondiabetic patients with hyperkalemia.

We advocate that GO be prospectively evaluated against GwI for the treatment of hyperkalemia in subjects without diabetes, against the endpoints being noninferiority in respect of efficacy and maintenance of euglycemia in respect of safety.

Disclosures

Nothing to declare.

Boughton et al.¹ reported a high incidence of hypoglycemia resulting from glucose-with-insulin (GwI) infusion used to treat acute hyperkalemia. This has been reported by other investigators—particularly in subjects without preexisting diabetes² and resonates with the experiences of clinicians practicing in Internal Medicine or Diabetes.

The authors suggested that patients at risk of hypoglycemia be identified and offered a regimen containing less insulin. However, for subjects without preexisting diagnosis and not at high risk of diabetes, we question the physiological logic and the safety basis for administering insulin.

Infusion of glucose only (GO) to subjects with intact pancreatic function and insulin sensitivity stimulates endogenous insulin secretion in a dose-dependent manner, resulting in a reduction in extracellular fluid potassium with no risk of hypoglycemia.^3,4

It is unclear why GwI historically entered mainstream practice rather than GO, but the rationale may have been based on the potential risks of paradoxical hyperglycemia-mediated hyperkalemia (HMK) being induced by GO. In practice, HMK was only observed in subjects with diabetes.⁵

As there is an ongoing need to reduce the impact of iatrogenic hypoglycemia, revisiting of the prematurely abandoned GO regimen in hyperkalemia management is warranted. Such approach may offer a safe and physiological alternative to GwI in nondiabetic patients with hyperkalemia.

We advocate that GO be prospectively evaluated against GwI for the treatment of hyperkalemia in subjects without diabetes, against the endpoints being noninferiority in respect of efficacy and maintenance of euglycemia in respect of safety.

Disclosures

Nothing to declare.

Boughton et al.¹ reported a high incidence of hypoglycemia resulting from glucose-with-insulin (GwI) infusion used to treat acute hyperkalemia. This has been reported by other investigators—particularly in subjects without preexisting diabetes² and resonates with the experiences of clinicians practicing in Internal Medicine or Diabetes.

The authors suggested that patients at risk of hypoglycemia be identified and offered a regimen containing less insulin. However, for subjects without preexisting diagnosis and not at high risk of diabetes, we question the physiological logic and the safety basis for administering insulin.

Infusion of glucose only (GO) to subjects with intact pancreatic function and insulin sensitivity stimulates endogenous insulin secretion in a dose-dependent manner, resulting in a reduction in extracellular fluid potassium with no risk of hypoglycemia.^3,4

It is unclear why GwI historically entered mainstream practice rather than GO, but the rationale may have been based on the potential risks of paradoxical hyperglycemia-mediated hyperkalemia (HMK) being induced by GO. In practice, HMK was only observed in subjects with diabetes.⁵

As there is an ongoing need to reduce the impact of iatrogenic hypoglycemia, revisiting of the prematurely abandoned GO regimen in hyperkalemia management is warranted. Such approach may offer a safe and physiological alternative to GwI in nondiabetic patients with hyperkalemia.

We advocate that GO be prospectively evaluated against GwI for the treatment of hyperkalemia in subjects without diabetes, against the endpoints being noninferiority in respect of efficacy and maintenance of euglycemia in respect of safety.

Disclosures

Nothing to declare.

With advancement in imaging techniques, incidental pulmonary nodules (IPNs) are routinely found on imaging studies. Depending on the size, an IPN has diagnostic uncertainty. Is it a benign finding? Will it progress to cancer? These questions have the potential to create anxiety for our patients. Between 2012 and 2014, 19,739 patients were discharged from hospitals in the United States with a diagnosis of a solitary pulmonary nodule.¹ Roughly 7,500 were discharged after an inpatient stay; the remainder from the emergency room. Aggregate costs for these visits totaled $49 million. The exact number of nodules receiving follow-up is unknown.

The Fleischner guidelines, updated in 2017, outline management for IPNs.² Depending on nodule size and patient risk factors, repeat imaging is either not indicated or one to two follow-up scans could be recommended. In this issue of the Journal of Hospital Medicine^®, two reports assess provider awareness of the Fleischner guidelines and examine the proportion of patients receiving follow-up.

Umscheid et al. surveyed hospitalists to understand their approach IPN management. Of 174 respondents, 42% were unfamiliar with the Fleischner guidelines.3 The authors proposed methods for improving provider awareness, including better communication between hospitalists and primary care providers, better documentation, and in the case of their institution, the development of an IPN consult team. The IPN consult team is composed of a nurse practitioner and pulmonologist. They inform primary care providers of patient findings and need for follow-up. If no follow-up is made, the team will see the patients in an IPN ambulatory clinic to ensure follow-up imaging is obtained.

Kwan et al. found that fewer than 50% of patients with high-risk new pulmonary nodules received follow-up.4 Although a single-site study, the study is consistent with prior work on tests pending at discharge, which essentially show that there are poor follow-up rates.^5,6 Follow-up was more likely when the IPN was mentioned in the discharge summary. This conclusion builds on previous work showing that IPNs are more likely to be included in a discharge summary if the nodule is noted in the report heading, the radiologist recommends further imaging, and the patient is discharged from a medicine service as opposed to a surgical service.7 IPN follow-up is less likely if results are mentioned in the findings section alone.⁵

IPN follow-up is a piece of a larger issue of how best to ensure appropriate follow-up of any tests pending after discharge. A systematic review of discharge interventions found improvement in follow-up when discharge summaries are combined with e-mail alerts.⁶ A study of the effects of integrated electronic health records (EHR) web modules with discharge specific instructions showed an increase in follow-up from 18% to 27%.8 Studies also consider provider-to-patient communication. One intervention uses the patient portal to remind patients to pick up their medications,9 finding a decrease in nonadherence from 65.5% to 22.2%. Engaging patients by way of patient portals and reminders are an effective way to hold both the physician and the patient accountable for follow-up. Mobile technologies studied in the emergency department show patient preferences toward texting to receive medication and appointment reminders.10 Given wide-spread adoption of mobile technologies,11 notification systems could leverage applications or texting modalities to keep patients informed of discharge appointments and follow-up imaging studies. Similar interventions could be designed for IPNs using the Fleischner guidelines, generating alerts when patients have not received follow-up imaging.

The number of IPNs identified in the hospital will likely remain in the tens of thousands. From the hospitalist perspective, the findings presented in this month’s Journal of Hospital Medicine suggest that patients be educated about their findings and recommended follow-up, that follow-up be arranged before discharge, and that findings are clearly documented for patients and primary care providers to review. More study into how to implement these enhancements is needed to guide how we focus educational, systems, and technological interventions. Further study is also needed to help understand the complexities of communication channels between hospitalists and primary care physicians. As hospitalist workflow is more integrated with the EHR and mobile technology, future interventions can facilitate follow-up, keeping all providers and, most importantly, the patient aware of the next steps in care.

Acknowledgments

Author support is provided by the South Texas Veterans Health Care System. The views expressed are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs.

Disclosures

The authors report no financial conflicts of interest.

With advancement in imaging techniques, incidental pulmonary nodules (IPNs) are routinely found on imaging studies. Depending on the size, an IPN has diagnostic uncertainty. Is it a benign finding? Will it progress to cancer? These questions have the potential to create anxiety for our patients. Between 2012 and 2014, 19,739 patients were discharged from hospitals in the United States with a diagnosis of a solitary pulmonary nodule.¹ Roughly 7,500 were discharged after an inpatient stay; the remainder from the emergency room. Aggregate costs for these visits totaled $49 million. The exact number of nodules receiving follow-up is unknown.

The Fleischner guidelines, updated in 2017, outline management for IPNs.² Depending on nodule size and patient risk factors, repeat imaging is either not indicated or one to two follow-up scans could be recommended. In this issue of the Journal of Hospital Medicine^®, two reports assess provider awareness of the Fleischner guidelines and examine the proportion of patients receiving follow-up.

Umscheid et al. surveyed hospitalists to understand their approach IPN management. Of 174 respondents, 42% were unfamiliar with the Fleischner guidelines.3 The authors proposed methods for improving provider awareness, including better communication between hospitalists and primary care providers, better documentation, and in the case of their institution, the development of an IPN consult team. The IPN consult team is composed of a nurse practitioner and pulmonologist. They inform primary care providers of patient findings and need for follow-up. If no follow-up is made, the team will see the patients in an IPN ambulatory clinic to ensure follow-up imaging is obtained.

Kwan et al. found that fewer than 50% of patients with high-risk new pulmonary nodules received follow-up.4 Although a single-site study, the study is consistent with prior work on tests pending at discharge, which essentially show that there are poor follow-up rates.^5,6 Follow-up was more likely when the IPN was mentioned in the discharge summary. This conclusion builds on previous work showing that IPNs are more likely to be included in a discharge summary if the nodule is noted in the report heading, the radiologist recommends further imaging, and the patient is discharged from a medicine service as opposed to a surgical service.7 IPN follow-up is less likely if results are mentioned in the findings section alone.⁵

IPN follow-up is a piece of a larger issue of how best to ensure appropriate follow-up of any tests pending after discharge. A systematic review of discharge interventions found improvement in follow-up when discharge summaries are combined with e-mail alerts.⁶ A study of the effects of integrated electronic health records (EHR) web modules with discharge specific instructions showed an increase in follow-up from 18% to 27%.8 Studies also consider provider-to-patient communication. One intervention uses the patient portal to remind patients to pick up their medications,9 finding a decrease in nonadherence from 65.5% to 22.2%. Engaging patients by way of patient portals and reminders are an effective way to hold both the physician and the patient accountable for follow-up. Mobile technologies studied in the emergency department show patient preferences toward texting to receive medication and appointment reminders.10 Given wide-spread adoption of mobile technologies,11 notification systems could leverage applications or texting modalities to keep patients informed of discharge appointments and follow-up imaging studies. Similar interventions could be designed for IPNs using the Fleischner guidelines, generating alerts when patients have not received follow-up imaging.

The number of IPNs identified in the hospital will likely remain in the tens of thousands. From the hospitalist perspective, the findings presented in this month’s Journal of Hospital Medicine suggest that patients be educated about their findings and recommended follow-up, that follow-up be arranged before discharge, and that findings are clearly documented for patients and primary care providers to review. More study into how to implement these enhancements is needed to guide how we focus educational, systems, and technological interventions. Further study is also needed to help understand the complexities of communication channels between hospitalists and primary care physicians. As hospitalist workflow is more integrated with the EHR and mobile technology, future interventions can facilitate follow-up, keeping all providers and, most importantly, the patient aware of the next steps in care.

Acknowledgments

Author support is provided by the South Texas Veterans Health Care System. The views expressed are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs.

Disclosures

The authors report no financial conflicts of interest.

With advancement in imaging techniques, incidental pulmonary nodules (IPNs) are routinely found on imaging studies. Depending on the size, an IPN has diagnostic uncertainty. Is it a benign finding? Will it progress to cancer? These questions have the potential to create anxiety for our patients. Between 2012 and 2014, 19,739 patients were discharged from hospitals in the United States with a diagnosis of a solitary pulmonary nodule.¹ Roughly 7,500 were discharged after an inpatient stay; the remainder from the emergency room. Aggregate costs for these visits totaled $49 million. The exact number of nodules receiving follow-up is unknown.

The Fleischner guidelines, updated in 2017, outline management for IPNs.² Depending on nodule size and patient risk factors, repeat imaging is either not indicated or one to two follow-up scans could be recommended. In this issue of the Journal of Hospital Medicine^®, two reports assess provider awareness of the Fleischner guidelines and examine the proportion of patients receiving follow-up.

Umscheid et al. surveyed hospitalists to understand their approach IPN management. Of 174 respondents, 42% were unfamiliar with the Fleischner guidelines.3 The authors proposed methods for improving provider awareness, including better communication between hospitalists and primary care providers, better documentation, and in the case of their institution, the development of an IPN consult team. The IPN consult team is composed of a nurse practitioner and pulmonologist. They inform primary care providers of patient findings and need for follow-up. If no follow-up is made, the team will see the patients in an IPN ambulatory clinic to ensure follow-up imaging is obtained.

Kwan et al. found that fewer than 50% of patients with high-risk new pulmonary nodules received follow-up.4 Although a single-site study, the study is consistent with prior work on tests pending at discharge, which essentially show that there are poor follow-up rates.^5,6 Follow-up was more likely when the IPN was mentioned in the discharge summary. This conclusion builds on previous work showing that IPNs are more likely to be included in a discharge summary if the nodule is noted in the report heading, the radiologist recommends further imaging, and the patient is discharged from a medicine service as opposed to a surgical service.7 IPN follow-up is less likely if results are mentioned in the findings section alone.⁵

IPN follow-up is a piece of a larger issue of how best to ensure appropriate follow-up of any tests pending after discharge. A systematic review of discharge interventions found improvement in follow-up when discharge summaries are combined with e-mail alerts.⁶ A study of the effects of integrated electronic health records (EHR) web modules with discharge specific instructions showed an increase in follow-up from 18% to 27%.8 Studies also consider provider-to-patient communication. One intervention uses the patient portal to remind patients to pick up their medications,9 finding a decrease in nonadherence from 65.5% to 22.2%. Engaging patients by way of patient portals and reminders are an effective way to hold both the physician and the patient accountable for follow-up. Mobile technologies studied in the emergency department show patient preferences toward texting to receive medication and appointment reminders.10 Given wide-spread adoption of mobile technologies,11 notification systems could leverage applications or texting modalities to keep patients informed of discharge appointments and follow-up imaging studies. Similar interventions could be designed for IPNs using the Fleischner guidelines, generating alerts when patients have not received follow-up imaging.

The number of IPNs identified in the hospital will likely remain in the tens of thousands. From the hospitalist perspective, the findings presented in this month’s Journal of Hospital Medicine suggest that patients be educated about their findings and recommended follow-up, that follow-up be arranged before discharge, and that findings are clearly documented for patients and primary care providers to review. More study into how to implement these enhancements is needed to guide how we focus educational, systems, and technological interventions. Further study is also needed to help understand the complexities of communication channels between hospitalists and primary care physicians. As hospitalist workflow is more integrated with the EHR and mobile technology, future interventions can facilitate follow-up, keeping all providers and, most importantly, the patient aware of the next steps in care.

Acknowledgments

Author support is provided by the South Texas Veterans Health Care System. The views expressed are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs.

Disclosures

The authors report no financial conflicts of interest.

Click here to access June 2019 Management of Neurologic Disorders in Federal Health Care

Table of Contents

• Early and Accurate Identification of Parkinson Disease Among US Veterans
• Proton Pump Inhibitor Use and Risk of Dementia in the Veteran Population
• Understanding Psychosis in a Veteran With a History of Combat and Multiple Sclerosis
• Hemolytic Uremic Syndrome With Severe Neurologic Complications in an Adult
• Research News: Neurologic Disorders

Click here to access June 2019 Management of Neurologic Disorders in Federal Health Care

Table of Contents

• Early and Accurate Identification of Parkinson Disease Among US Veterans
• Proton Pump Inhibitor Use and Risk of Dementia in the Veteran Population
• Understanding Psychosis in a Veteran With a History of Combat and Multiple Sclerosis
• Hemolytic Uremic Syndrome With Severe Neurologic Complications in an Adult
• Research News: Neurologic Disorders

Click here to access June 2019 Management of Neurologic Disorders in Federal Health Care

Table of Contents

• Early and Accurate Identification of Parkinson Disease Among US Veterans
• Proton Pump Inhibitor Use and Risk of Dementia in the Veteran Population
• Understanding Psychosis in a Veteran With a History of Combat and Multiple Sclerosis
• Hemolytic Uremic Syndrome With Severe Neurologic Complications in an Adult
• Research News: Neurologic Disorders

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

[polldaddy:10332867]

TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

[polldaddy:10332867]

TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

[polldaddy:10332867]

TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

Dr. Nasrallah’s “Psychiatry and neurology: Sister neuroscience specialties with different approaches to the brain” (From the Editor, Current Psychiatry, March 2019, p. 4-5, 8), which explored the distinctions and commonalities between neurology and psychiatry, was important and timely. It was particularly worthwhile to discuss with my medical students the accompanying Table, to better answer the question, “What is the difference between these fields?” However, I believe a critical component of this discussion wasn’t mentioned: the transcendent nature of psychiatry, addressing the full complexity of the human experience beyond the clinical milieu.

In mathematics, chaos theory deals with the impossible complexity of simplicity. From primitive initial states, self-interacting systems give rise to short-term predictability, but an unpredictable long-term. Classically, this is illustrated as a hurricane born from the flapping of a butterfly’s wings. Neurology has found great clinical utility in understanding butterfly wings. However, psychiatry forsakes simplicity for complexity: it dives into the emergent systems that arise from self-interacting neurons, asking us to stand within the eye of the hurricane and understand it in its entirety. Psychiatry asks us to transcend the traditional medical focus of discrete physiological mechanisms, and ask—from the standpoint of biologic, social, and spiritual well-being—how can we calm the hurricane?

Psychiatry once had a widely-encompassing understanding of its remit: to appreciate the multifaceted experience of the human life and grant succor to the fractured or anguished soul. In such times, psychiatry was a popular destination for seniors graduating in the United States. Annually, 7% to 10% of US graduates chose psychiatry as a career, and continued to do so until the late 1970s.¹ In the 1970s, the reductive understanding of the mind increased in prominence, and the role of psychiatry transitioned to one similar to that of other medical specialties: putting patients in boxes, and chronically titrating their medications. The interest of graduating seniors waned alongside the scope of our interest: in 1977, only 4.4% of US graduates pursued psychiatry.² In 2019, 4.06% of graduating senior applications were to the field of psychiatry.³ (This is not meant to undervalue the quality of international medical graduates, but to focus on local trends in cultural values.)

Psychiatry offers diagnostic and therapeutic avenues that are traditionally undervalued in other fields of medicine. Nephrosis may not care if a patient feels that his or her life is spiritually satisfying and their actions meaningful. However, a patient’s anguish at his reduced functional status does not care for whether his albumin level is normalized—he requires that his suffering be recognized, and that we make an earnest effort to cloak “the shameful nakedness of pain.”⁴

Psychiatry also makes unique demands of, and offers benefits to, the practitioner. Neurologists complete their residencies feeling that their clinical acumen has increased: “I can formulate a thorough differential now.” Psychiatry asks us not only to cultivate technical proficiency, but also wisdom. The prolonged reflection on the quality and nature of human experience, and the need to guide such patients in a manner far wider and more meaningful in scope than their serotonin pathways, offers the opportunity to emerge from residency a more mindful and grateful human being.

Ultimately, the loss of this sense of scope has not been a failure of medical education. It has been a surrender of the current generation of psychiatry attendings. We have ceded responsibility for the social and spiritual care of our patients to other fields, or to no one at all. If we give up on understanding the hurricane, how can we be surprised that students prefer to chase butterflies?

James Steinberg, MPH, OMS-IV
New York Institute of Technology
College of Osteopathic Medicine
Old Westbury, New York

Robert Barris, MD
Director
Inpatient Psychiatric Services
Nassau University Medical Center
East Meadow, New York

References
1. Sierles FS, Taylor MA. Decline of U.S. medical student career choice of psychiatry and what to do about it. Am J Psychiatry. 1995;152(10):1416-1426.
2. Results and data: main residency match. NRMP data. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2013/08/resultsanddata1984.pdf. Published May 1984. Accessed May 8, 2019.
3. Advanced Data Tables. The Match 2019. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2019/03/Advance-Data-Tables-2019_WWW.pdf. Published March 2019. Accessed May 8, 2019.
4. Kipling R. Doctors. In: Kipling: poems (Everyman’s Library Pocket Poets Series). New York, NY: Random House. 2007:234.

Dr. Nasrallah responds

Thank you, Mr. Steinberg and Dr. Barris, for your comments about my editorial. I genuinely enjoyed the eloquence of your letter. In computers, which we all own and use, hardware is indispensable because it enables us to exploit the software, but the richness of the software is far more interesting than the hardware for the creative productivity of humans. So what you say is correct: The brain is the tangible hardware, and the transcendent mind is the splendid software that encompasses all that makes us human, such as thought, affect, cognition, and behavior. I certainly hope that the psychiatry training programs never reduce the practice of psychiatry to prescribing pills to suppress symptoms. Our patients with psychiatric illness deserve much more than that, and you obviously understand that. But just as neurology should not be mindless, psychiatry should not be brainless. Both specialties are 2 sides of the glorious discipline of neuroscience. By the way, I am pleased and proud to tell you that 13% of the graduating medical school seniors at our university have chosen psychiatry as a career.

Henry A. Nasrallah, MD
Editor-in-Chief
The Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Continue to: Perspectives on motherhood and psychiatry

 

 

Perspectives on motherhood and psychiatry

I very much enjoyed Drs. Helen M. Farrell’s and Katherine A. Kosman’s recent article “Motherhood and the working psychiatrist” (Psychiatry 2.0, Current Psychiatry, March 2019, p. 40-43). I would love to see a series of similar articles and opinion pieces highlighting different perspectives from other practicing psychiatrists who are also parents—in particular, mothers. I completely relate to the dilemma you pose about the multiple duties one has as both a mother and physician, as well as feeling the pull towards honoring our understanding of attachment in the face of conflicting responsibilities. I imagine it’s an experience to which many can relate. 

Christina Ford, MD
Private psychiatric practice
Los Angeles, California

I doubt that anyone—male or female—would argue against the points made by Drs. Farrell and Kosman’s “Motherhood and the working psychiatrist,” which emphasized the need for breaking down the barriers that continue to exist for female physicians who choose to balance their careers with motherhood. As a female psychiatrist who has known since high school that I would choose to remain child-free, I would like to add a different perspective to this discussion and possibly help represent the 20% of women, age 40 to 44, with an MD or PhD who are also child-free.¹

While Drs. Farrell and Kosman referenced many assumptions made about working physician mothers, I have not been able to move through medical school, residency, and my career without battling certain assumptions as well. Although every mother is a woman, logic dictates that the converse—every woman is a mother—is certainly not true. However, when interviewing for residency, I was paired specifically with a female attending who had children, and I was told that I could ask her questions about how to balance work-life and raising a family, despite the fact that I did not say or indicate that I had any interest in having such a conversation. There is also the assumption (sometimes more explicit than others) that those of us without children are missing out on something—that we are not included in the “having it all” category. However, in my mind, “having it all” means having the choice to remain child-free, to focus more intensely on my career, to travel when I want, and to own a white couch—without feeling the social obligation to fulfill a role in which I really have no interest.

Cherishing that ability to focus more on my career, however, does not imply that I am boundlessly able and willing to take extra calls, work holidays, or cover for all my colleagues with children (which is also a common assumption). And while I may not be a caregiver to children, that should not detract from the devotion and time I want to spend helping my parents, relatives, and friends.

The article also made the case that facilities, medical schools, and residency programs need to implement policies and procedures that guide the development of accommodations, such as flexible scheduling and lactation rooms, to meet the needs of trainees and physicians without having to jump through hoops or rely on colleagues for coverage and other assistance. Having been in situations where such policies and procedures were not in place, I can affirm that the absence of such guidelines leads not only parents but also child-free physicians to feeling unnecessarily stressed. There was no clear coverage in place when fellow classmates in my residency program went on maternity leave. Essentially, everyone else was expected to step up and take on the additional caseloads, leading the pregnant classmates to try to time things around rotations where there were lighter demands or more residents assigned—not a simple task by any means.

Post-residency, there have been continued challenges. At one point, I was working in a clinic with 2 other female psychiatrists, one of whom was making plans to take maternity leave. During a meeting with our supervisors, the other physician and I were told that we were taking on the third doctor’s patients (without any extension of our own hours or reimbursement) while she was on leave. In addition to disgruntlement over the extra work being sprung on us, I pointed out that this would, in effect, make the third physician’s role obsolete. If 2 of us were able to do the work of 3, what would be the point in keeping her position when she returned? I was assured that this wouldn’t be the case. We dealt with the weeks of covering additional patients, and when she returned from leave, she was asked to shift some of her hours to a different (and, in my opinion, less desirable) clinic.

So, yes, it is incumbent upon facilities and training programs to take responsibility and to remove the barriers that make the jobs of female physicians with children even more challenging than they need to be. This can benefit not only those physicians and their children, but also their colleagues and, ultimately, the patients, who often bear the brunt of stressed, burnt-out physicians and disorganized programs. While I am not going to take a stance on whether it truly takes a village to raise a child, I certainly do not think that it should take a village to organize maternity leave and lactation rooms.

Jessica L. Langenhan, MD, MBA, CHCQM
Medical DirectorBeacon Health Options
Cypress, California

Reference
1. Livingston G. Childlessness. Pew Research Center. https://www.pewsocialtrends.org/2015/05/07/childlessness/. Published May 7, 2015. Accessed May 9, 2019.

Dr. Nasrallah’s “Psychiatry and neurology: Sister neuroscience specialties with different approaches to the brain” (From the Editor, Current Psychiatry, March 2019, p. 4-5, 8), which explored the distinctions and commonalities between neurology and psychiatry, was important and timely. It was particularly worthwhile to discuss with my medical students the accompanying Table, to better answer the question, “What is the difference between these fields?” However, I believe a critical component of this discussion wasn’t mentioned: the transcendent nature of psychiatry, addressing the full complexity of the human experience beyond the clinical milieu.

In mathematics, chaos theory deals with the impossible complexity of simplicity. From primitive initial states, self-interacting systems give rise to short-term predictability, but an unpredictable long-term. Classically, this is illustrated as a hurricane born from the flapping of a butterfly’s wings. Neurology has found great clinical utility in understanding butterfly wings. However, psychiatry forsakes simplicity for complexity: it dives into the emergent systems that arise from self-interacting neurons, asking us to stand within the eye of the hurricane and understand it in its entirety. Psychiatry asks us to transcend the traditional medical focus of discrete physiological mechanisms, and ask—from the standpoint of biologic, social, and spiritual well-being—how can we calm the hurricane?

Psychiatry once had a widely-encompassing understanding of its remit: to appreciate the multifaceted experience of the human life and grant succor to the fractured or anguished soul. In such times, psychiatry was a popular destination for seniors graduating in the United States. Annually, 7% to 10% of US graduates chose psychiatry as a career, and continued to do so until the late 1970s.¹ In the 1970s, the reductive understanding of the mind increased in prominence, and the role of psychiatry transitioned to one similar to that of other medical specialties: putting patients in boxes, and chronically titrating their medications. The interest of graduating seniors waned alongside the scope of our interest: in 1977, only 4.4% of US graduates pursued psychiatry.² In 2019, 4.06% of graduating senior applications were to the field of psychiatry.³ (This is not meant to undervalue the quality of international medical graduates, but to focus on local trends in cultural values.)

Psychiatry offers diagnostic and therapeutic avenues that are traditionally undervalued in other fields of medicine. Nephrosis may not care if a patient feels that his or her life is spiritually satisfying and their actions meaningful. However, a patient’s anguish at his reduced functional status does not care for whether his albumin level is normalized—he requires that his suffering be recognized, and that we make an earnest effort to cloak “the shameful nakedness of pain.”⁴

Psychiatry also makes unique demands of, and offers benefits to, the practitioner. Neurologists complete their residencies feeling that their clinical acumen has increased: “I can formulate a thorough differential now.” Psychiatry asks us not only to cultivate technical proficiency, but also wisdom. The prolonged reflection on the quality and nature of human experience, and the need to guide such patients in a manner far wider and more meaningful in scope than their serotonin pathways, offers the opportunity to emerge from residency a more mindful and grateful human being.

Ultimately, the loss of this sense of scope has not been a failure of medical education. It has been a surrender of the current generation of psychiatry attendings. We have ceded responsibility for the social and spiritual care of our patients to other fields, or to no one at all. If we give up on understanding the hurricane, how can we be surprised that students prefer to chase butterflies?

James Steinberg, MPH, OMS-IV
New York Institute of Technology
College of Osteopathic Medicine
Old Westbury, New York

Robert Barris, MD
Director
Inpatient Psychiatric Services
Nassau University Medical Center
East Meadow, New York

References
1. Sierles FS, Taylor MA. Decline of U.S. medical student career choice of psychiatry and what to do about it. Am J Psychiatry. 1995;152(10):1416-1426.
2. Results and data: main residency match. NRMP data. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2013/08/resultsanddata1984.pdf. Published May 1984. Accessed May 8, 2019.
3. Advanced Data Tables. The Match 2019. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2019/03/Advance-Data-Tables-2019_WWW.pdf. Published March 2019. Accessed May 8, 2019.
4. Kipling R. Doctors. In: Kipling: poems (Everyman’s Library Pocket Poets Series). New York, NY: Random House. 2007:234.

Dr. Nasrallah responds

Thank you, Mr. Steinberg and Dr. Barris, for your comments about my editorial. I genuinely enjoyed the eloquence of your letter. In computers, which we all own and use, hardware is indispensable because it enables us to exploit the software, but the richness of the software is far more interesting than the hardware for the creative productivity of humans. So what you say is correct: The brain is the tangible hardware, and the transcendent mind is the splendid software that encompasses all that makes us human, such as thought, affect, cognition, and behavior. I certainly hope that the psychiatry training programs never reduce the practice of psychiatry to prescribing pills to suppress symptoms. Our patients with psychiatric illness deserve much more than that, and you obviously understand that. But just as neurology should not be mindless, psychiatry should not be brainless. Both specialties are 2 sides of the glorious discipline of neuroscience. By the way, I am pleased and proud to tell you that 13% of the graduating medical school seniors at our university have chosen psychiatry as a career.

Henry A. Nasrallah, MD
Editor-in-Chief
The Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Continue to: Perspectives on motherhood and psychiatry

 

 

Perspectives on motherhood and psychiatry

I very much enjoyed Drs. Helen M. Farrell’s and Katherine A. Kosman’s recent article “Motherhood and the working psychiatrist” (Psychiatry 2.0, Current Psychiatry, March 2019, p. 40-43). I would love to see a series of similar articles and opinion pieces highlighting different perspectives from other practicing psychiatrists who are also parents—in particular, mothers. I completely relate to the dilemma you pose about the multiple duties one has as both a mother and physician, as well as feeling the pull towards honoring our understanding of attachment in the face of conflicting responsibilities. I imagine it’s an experience to which many can relate. 

Christina Ford, MD
Private psychiatric practice
Los Angeles, California

I doubt that anyone—male or female—would argue against the points made by Drs. Farrell and Kosman’s “Motherhood and the working psychiatrist,” which emphasized the need for breaking down the barriers that continue to exist for female physicians who choose to balance their careers with motherhood. As a female psychiatrist who has known since high school that I would choose to remain child-free, I would like to add a different perspective to this discussion and possibly help represent the 20% of women, age 40 to 44, with an MD or PhD who are also child-free.¹

While Drs. Farrell and Kosman referenced many assumptions made about working physician mothers, I have not been able to move through medical school, residency, and my career without battling certain assumptions as well. Although every mother is a woman, logic dictates that the converse—every woman is a mother—is certainly not true. However, when interviewing for residency, I was paired specifically with a female attending who had children, and I was told that I could ask her questions about how to balance work-life and raising a family, despite the fact that I did not say or indicate that I had any interest in having such a conversation. There is also the assumption (sometimes more explicit than others) that those of us without children are missing out on something—that we are not included in the “having it all” category. However, in my mind, “having it all” means having the choice to remain child-free, to focus more intensely on my career, to travel when I want, and to own a white couch—without feeling the social obligation to fulfill a role in which I really have no interest.

Cherishing that ability to focus more on my career, however, does not imply that I am boundlessly able and willing to take extra calls, work holidays, or cover for all my colleagues with children (which is also a common assumption). And while I may not be a caregiver to children, that should not detract from the devotion and time I want to spend helping my parents, relatives, and friends.

The article also made the case that facilities, medical schools, and residency programs need to implement policies and procedures that guide the development of accommodations, such as flexible scheduling and lactation rooms, to meet the needs of trainees and physicians without having to jump through hoops or rely on colleagues for coverage and other assistance. Having been in situations where such policies and procedures were not in place, I can affirm that the absence of such guidelines leads not only parents but also child-free physicians to feeling unnecessarily stressed. There was no clear coverage in place when fellow classmates in my residency program went on maternity leave. Essentially, everyone else was expected to step up and take on the additional caseloads, leading the pregnant classmates to try to time things around rotations where there were lighter demands or more residents assigned—not a simple task by any means.

Post-residency, there have been continued challenges. At one point, I was working in a clinic with 2 other female psychiatrists, one of whom was making plans to take maternity leave. During a meeting with our supervisors, the other physician and I were told that we were taking on the third doctor’s patients (without any extension of our own hours or reimbursement) while she was on leave. In addition to disgruntlement over the extra work being sprung on us, I pointed out that this would, in effect, make the third physician’s role obsolete. If 2 of us were able to do the work of 3, what would be the point in keeping her position when she returned? I was assured that this wouldn’t be the case. We dealt with the weeks of covering additional patients, and when she returned from leave, she was asked to shift some of her hours to a different (and, in my opinion, less desirable) clinic.

So, yes, it is incumbent upon facilities and training programs to take responsibility and to remove the barriers that make the jobs of female physicians with children even more challenging than they need to be. This can benefit not only those physicians and their children, but also their colleagues and, ultimately, the patients, who often bear the brunt of stressed, burnt-out physicians and disorganized programs. While I am not going to take a stance on whether it truly takes a village to raise a child, I certainly do not think that it should take a village to organize maternity leave and lactation rooms.

Jessica L. Langenhan, MD, MBA, CHCQM
Medical DirectorBeacon Health Options
Cypress, California

Reference
1. Livingston G. Childlessness. Pew Research Center. https://www.pewsocialtrends.org/2015/05/07/childlessness/. Published May 7, 2015. Accessed May 9, 2019.

Dr. Nasrallah’s “Psychiatry and neurology: Sister neuroscience specialties with different approaches to the brain” (From the Editor, Current Psychiatry, March 2019, p. 4-5, 8), which explored the distinctions and commonalities between neurology and psychiatry, was important and timely. It was particularly worthwhile to discuss with my medical students the accompanying Table, to better answer the question, “What is the difference between these fields?” However, I believe a critical component of this discussion wasn’t mentioned: the transcendent nature of psychiatry, addressing the full complexity of the human experience beyond the clinical milieu.

In mathematics, chaos theory deals with the impossible complexity of simplicity. From primitive initial states, self-interacting systems give rise to short-term predictability, but an unpredictable long-term. Classically, this is illustrated as a hurricane born from the flapping of a butterfly’s wings. Neurology has found great clinical utility in understanding butterfly wings. However, psychiatry forsakes simplicity for complexity: it dives into the emergent systems that arise from self-interacting neurons, asking us to stand within the eye of the hurricane and understand it in its entirety. Psychiatry asks us to transcend the traditional medical focus of discrete physiological mechanisms, and ask—from the standpoint of biologic, social, and spiritual well-being—how can we calm the hurricane?

Psychiatry once had a widely-encompassing understanding of its remit: to appreciate the multifaceted experience of the human life and grant succor to the fractured or anguished soul. In such times, psychiatry was a popular destination for seniors graduating in the United States. Annually, 7% to 10% of US graduates chose psychiatry as a career, and continued to do so until the late 1970s.¹ In the 1970s, the reductive understanding of the mind increased in prominence, and the role of psychiatry transitioned to one similar to that of other medical specialties: putting patients in boxes, and chronically titrating their medications. The interest of graduating seniors waned alongside the scope of our interest: in 1977, only 4.4% of US graduates pursued psychiatry.² In 2019, 4.06% of graduating senior applications were to the field of psychiatry.³ (This is not meant to undervalue the quality of international medical graduates, but to focus on local trends in cultural values.)

Psychiatry offers diagnostic and therapeutic avenues that are traditionally undervalued in other fields of medicine. Nephrosis may not care if a patient feels that his or her life is spiritually satisfying and their actions meaningful. However, a patient’s anguish at his reduced functional status does not care for whether his albumin level is normalized—he requires that his suffering be recognized, and that we make an earnest effort to cloak “the shameful nakedness of pain.”⁴

Psychiatry also makes unique demands of, and offers benefits to, the practitioner. Neurologists complete their residencies feeling that their clinical acumen has increased: “I can formulate a thorough differential now.” Psychiatry asks us not only to cultivate technical proficiency, but also wisdom. The prolonged reflection on the quality and nature of human experience, and the need to guide such patients in a manner far wider and more meaningful in scope than their serotonin pathways, offers the opportunity to emerge from residency a more mindful and grateful human being.

Ultimately, the loss of this sense of scope has not been a failure of medical education. It has been a surrender of the current generation of psychiatry attendings. We have ceded responsibility for the social and spiritual care of our patients to other fields, or to no one at all. If we give up on understanding the hurricane, how can we be surprised that students prefer to chase butterflies?

James Steinberg, MPH, OMS-IV
New York Institute of Technology
College of Osteopathic Medicine
Old Westbury, New York

Robert Barris, MD
Director
Inpatient Psychiatric Services
Nassau University Medical Center
East Meadow, New York

References
1. Sierles FS, Taylor MA. Decline of U.S. medical student career choice of psychiatry and what to do about it. Am J Psychiatry. 1995;152(10):1416-1426.
2. Results and data: main residency match. NRMP data. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2013/08/resultsanddata1984.pdf. Published May 1984. Accessed May 8, 2019.
3. Advanced Data Tables. The Match 2019. The National Resident Matching Program. https://mk0nrmpcikgb8jxyd19h.kinstacdn.com/wp-content/uploads/2019/03/Advance-Data-Tables-2019_WWW.pdf. Published March 2019. Accessed May 8, 2019.
4. Kipling R. Doctors. In: Kipling: poems (Everyman’s Library Pocket Poets Series). New York, NY: Random House. 2007:234.

Dr. Nasrallah responds

Thank you, Mr. Steinberg and Dr. Barris, for your comments about my editorial. I genuinely enjoyed the eloquence of your letter. In computers, which we all own and use, hardware is indispensable because it enables us to exploit the software, but the richness of the software is far more interesting than the hardware for the creative productivity of humans. So what you say is correct: The brain is the tangible hardware, and the transcendent mind is the splendid software that encompasses all that makes us human, such as thought, affect, cognition, and behavior. I certainly hope that the psychiatry training programs never reduce the practice of psychiatry to prescribing pills to suppress symptoms. Our patients with psychiatric illness deserve much more than that, and you obviously understand that. But just as neurology should not be mindless, psychiatry should not be brainless. Both specialties are 2 sides of the glorious discipline of neuroscience. By the way, I am pleased and proud to tell you that 13% of the graduating medical school seniors at our university have chosen psychiatry as a career.

Henry A. Nasrallah, MD
Editor-in-Chief
The Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Continue to: Perspectives on motherhood and psychiatry

 

 

Perspectives on motherhood and psychiatry

I very much enjoyed Drs. Helen M. Farrell’s and Katherine A. Kosman’s recent article “Motherhood and the working psychiatrist” (Psychiatry 2.0, Current Psychiatry, March 2019, p. 40-43). I would love to see a series of similar articles and opinion pieces highlighting different perspectives from other practicing psychiatrists who are also parents—in particular, mothers. I completely relate to the dilemma you pose about the multiple duties one has as both a mother and physician, as well as feeling the pull towards honoring our understanding of attachment in the face of conflicting responsibilities. I imagine it’s an experience to which many can relate. 

Christina Ford, MD
Private psychiatric practice
Los Angeles, California

I doubt that anyone—male or female—would argue against the points made by Drs. Farrell and Kosman’s “Motherhood and the working psychiatrist,” which emphasized the need for breaking down the barriers that continue to exist for female physicians who choose to balance their careers with motherhood. As a female psychiatrist who has known since high school that I would choose to remain child-free, I would like to add a different perspective to this discussion and possibly help represent the 20% of women, age 40 to 44, with an MD or PhD who are also child-free.¹

While Drs. Farrell and Kosman referenced many assumptions made about working physician mothers, I have not been able to move through medical school, residency, and my career without battling certain assumptions as well. Although every mother is a woman, logic dictates that the converse—every woman is a mother—is certainly not true. However, when interviewing for residency, I was paired specifically with a female attending who had children, and I was told that I could ask her questions about how to balance work-life and raising a family, despite the fact that I did not say or indicate that I had any interest in having such a conversation. There is also the assumption (sometimes more explicit than others) that those of us without children are missing out on something—that we are not included in the “having it all” category. However, in my mind, “having it all” means having the choice to remain child-free, to focus more intensely on my career, to travel when I want, and to own a white couch—without feeling the social obligation to fulfill a role in which I really have no interest.

Cherishing that ability to focus more on my career, however, does not imply that I am boundlessly able and willing to take extra calls, work holidays, or cover for all my colleagues with children (which is also a common assumption). And while I may not be a caregiver to children, that should not detract from the devotion and time I want to spend helping my parents, relatives, and friends.

The article also made the case that facilities, medical schools, and residency programs need to implement policies and procedures that guide the development of accommodations, such as flexible scheduling and lactation rooms, to meet the needs of trainees and physicians without having to jump through hoops or rely on colleagues for coverage and other assistance. Having been in situations where such policies and procedures were not in place, I can affirm that the absence of such guidelines leads not only parents but also child-free physicians to feeling unnecessarily stressed. There was no clear coverage in place when fellow classmates in my residency program went on maternity leave. Essentially, everyone else was expected to step up and take on the additional caseloads, leading the pregnant classmates to try to time things around rotations where there were lighter demands or more residents assigned—not a simple task by any means.

Post-residency, there have been continued challenges. At one point, I was working in a clinic with 2 other female psychiatrists, one of whom was making plans to take maternity leave. During a meeting with our supervisors, the other physician and I were told that we were taking on the third doctor’s patients (without any extension of our own hours or reimbursement) while she was on leave. In addition to disgruntlement over the extra work being sprung on us, I pointed out that this would, in effect, make the third physician’s role obsolete. If 2 of us were able to do the work of 3, what would be the point in keeping her position when she returned? I was assured that this wouldn’t be the case. We dealt with the weeks of covering additional patients, and when she returned from leave, she was asked to shift some of her hours to a different (and, in my opinion, less desirable) clinic.

So, yes, it is incumbent upon facilities and training programs to take responsibility and to remove the barriers that make the jobs of female physicians with children even more challenging than they need to be. This can benefit not only those physicians and their children, but also their colleagues and, ultimately, the patients, who often bear the brunt of stressed, burnt-out physicians and disorganized programs. While I am not going to take a stance on whether it truly takes a village to raise a child, I certainly do not think that it should take a village to organize maternity leave and lactation rooms.

Jessica L. Langenhan, MD, MBA, CHCQM
Medical DirectorBeacon Health Options
Cypress, California

Reference
1. Livingston G. Childlessness. Pew Research Center. https://www.pewsocialtrends.org/2015/05/07/childlessness/. Published May 7, 2015. Accessed May 9, 2019.