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‘Major advance’: Sotorasib benefit persists in KRAS+ NSCLC
NEW ORLEANS – with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).
The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.
That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.
“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.
Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.”
In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.
Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.
“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.
He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”
New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”
At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.
“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.
“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
Tarnished triumph
As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.
“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
Long follow-up
The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.
The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.
Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.
Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.
Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.
At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.
Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.
Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.
Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.
In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.
The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.
Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).
The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.
That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.
“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.
Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.”
In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.
Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.
“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.
He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”
New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”
At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.
“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.
“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
Tarnished triumph
As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.
“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
Long follow-up
The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.
The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.
Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.
Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.
Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.
At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.
Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.
Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.
Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.
In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.
The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.
Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – with the first-in-class KRAS inhibitor sotorasib (Lumakras, Amgen).
The finding comes from an analysis of long-term follow-up data from the CodeBreaK100 trial, which showed a 2-year overall survival (OS) rate of 32.5% in pretreated patients with KRASG12C-mutant disease.
That rate compares favorably with historical data on NSCLC therapies, said Grace K. Dy, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.
“We expect about half of that [survival rate] in patients who are treated with docetaxel,” she said in a plenary session at the annual meeting of the American Association for Cancer Research.
Sotorasib was approved by the Food and Drug Administration in May 2021 as the first drug for patients with NSCLC and KRAS mutations and was described as a “historic milestone.”
In this most recent analysis, which combined data from patients enrolled in phases 1 and 2 of the trial, the “objective response rate of 41% of patients was achieved with sotorasib, with a durable [disease] control rate of 84% and a median duration of response of 12.3 months, with no new safety signals emerging,” she said.
Nearly one-fourth of patients saw long-term benefit, as defined by progression-free survival of at least 12 months, and this long-term benefit was seen across variant allele frequencies of KRASG12C, programmed death–ligand 1 (PD-L1) tumor proportion score, and other comutations, she noted.
“KRASG12C inhibitors represent a major advance in the treatment of KRAS-mutant lung cancers and other types as well,” said invited discussant Mark M. Awad, MD, PhD, director of clinical research at the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center, Boston.
He cautioned, however, that “the therapeutic efficacy of these G12C inhibitors is currently limited by several things, including patient factors, intrinsic biology, and the emergence of complex resistance mechanisms.”
New approaches will be needed, he said, “to delay and overcome drug resistance to hopefully keep kicking cancer’s KRAS.”
At a media briefing where Dr. Dy presented the data prior to the oral abstract session, moderator Timothy A. Yap, MBBS, PhD, from the University of Texas MD Anderson Cancer Center, Houston, commented that the development of drug resistance is common in oncology.
“That is exactly why we’re now actively working on multiple different combinatorial approaches in the clinic. There have been pretty compelling data published from Mirati [Therapeutics] and from other companies, from Amgen, that really show the resistance mechanisms that actually come about upon monotherapy with KRASG12C inhibitors, including CDK4/6, including P13K-Akt pathways,” he said.
“The solution there really is, No. 1, we need to identify proactively the resistance mechanisms involved and driving each cancer’s resistance, and No. 2, then apply the combinatorial agent, to bring in a combination that’s a rational approach to match a patient’s molecular profile upon resistance,” he said.
Tarnished triumph
As previously reported, sotorasib was hailed as “a triumph of drug discovery” when early results of the trial were reported at the European Society of Medical Oncology annual meeting in 2020.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
But as Dr. Awad reported at the 2021 AACR annual meeting, the efficacy of sotorasib and other KRAS inhibitors in development has been threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Dr. Awad reported that among 30 patients with NSCLC or colorectal cancer bearing the KRASG12C mutation who had disease progression while being treated with the investigational inhibitor adagrasib in clinical trials, investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to the drug.
“Diverse mechanisms confer resistance to the KRASG12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” he said.
Long follow-up
The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.
The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.
Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.
Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.
Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.
At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.
Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.
Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.
Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.
In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.
The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.
Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.
A version of this article first appeared on Medscape.com.
AT AACR 2022
Breast anatomy and augmentation in transfeminine individuals
Augmentation mammaplasty, otherwise known as a breast augmentation, is one of the most common cosmetic procedures performed in cisgender females. Gynecologists routinely perform annual breast examinations and order screening mammography in cisgender women with breast implants. Similarly, there is an increasing number of transgender women seeking breast augmentation – with approximately 60%-70% of patients having desired or undergone the procedure.1 Consequently, these patients are instructed by their surgeons to follow up with gynecologists for annual examinations and screening. While there are many similarities in technique and procedure, there are nuances in patient demographics, anatomy, and surgical technique that obstetricians/gynecologists should be aware of when examining these patients or prior to referring them to a surgeon for augmentation.2
Many patients who are dissatisfied with breast size from hormone therapy alone will seek out augmentation mammaplasty. In patients taking estrogen for hormone therapy, breast growth will commence around 2-3 months and peak over 1-2 years.3 Unlike chest surgery for transmasculine individuals, it is recommended that transfeminine patients seeking breast augmentation wait a minimum of 12 months before to surgery to allow for maximum breast enlargement. As with breast growth in cisgender females, the extent of breast development is multifactorial and varies from individual to individual. Current literature does not suggest that estrogen type or dose affects the ultimate breast size; however, younger age, tissue sensitivity, and body weight may affect breast volume.3 Referral to a genetic counselor and preoperative imaging may be necessary if a patient has a history concerning for a genetic or familial predisposition to breast cancer.
Implant selection and placement is determined by a variety of factors. While the overall principles of augmentation mammaplasty are essentially the same, there are anatomic differences in transfeminine patients that surgeons must take into consideration at the time of the consultation and during the surgery itself. For example, the pectoralis major muscle is more defined, there is a longer sternal notch-to-nipple distance, the chest wall is broader and more barrel-shaped, and there is a shorter distance between the nipple and the inframammary crease.2-4 As a result of the broader chest wall, it is extremely difficult to achieve central cleavage even with larger implant selection. The surgeon must also ensure that the nipple and areola overlie the implant centrally. Medial placement of the implant will result in lateral displacement of the nipples, which can have an unsatisfactory cosmetic appearance.
Incision location can be axillary, inframammary, or even transareolar, although the latter is less common due to the smaller areolar size and larger implant choice.3 If the inframammary incision is used, it should be placed lower than the natural inframammary fold because the distance between the inferior areolar margin and inframammary fold is shorter and will expand after the implant is placed.4 While both saline and silicone implants are available, many surgeons (myself included), favor more form-stable silicone implants. Given the association between anaplastic large-cell lymphoma and textured implants, many surgeons also use nontextured, or smooth, cohesive gel silicone implants.5
Pocket selection of the implant itself can be subglandular – directly under the breast mound – or subpectoral – behind the pectoralis muscle. For patients with a pinch test of greater than 1.5 cm (outside of the area of the breast bud), good skin softening, and marked pectoralis hypertrophy, subglandular placement is reasonable.6 In thin patients with minimal breast development, subglandular placement can result in a “double-mound” appearance and can lead to visible implant edges on the periphery.6 Use of the subpectoral plane is more common and is associated with less implant visibility due to an increased amount of soft-tissue coverage and has lower rates of capsular contracture.4 However, due to the more robust pectoralis muscle in transfeminine patients, implant displacement can occur more frequently compared to subglandular placement. The surgeon and patient must have a thorough discussion about the location of the incision, implant material, and pocket placement along with the benefits and complications of the surgical plan.
Complications of augmentation mammaplasty are rare. However, when they occur it can include capsular contracture, breast asymmetry, hematoma formation, loss of nipple sensation, implant malposition, implant displacement below the inframammary crease, implant rupture, and need for revisional surgery.7 If an obstetrician/gynecologist observes any of the aforementioned findings in a postoperative patient, consultation and referral to a plastic surgeon is imperative.
Postoperative assessment and screening are mandatory in all patients who undergo breast augmentation. It is important for the gynecologist to note the incision placement, know the type of implant used (saline or silicone), and delineate where the implant was placed. If silicone implants are used, breast MRI is more sensitive in detecting implant rupture compared to mammography alone. Given the relatively poor epidemiologic data on breast cancer in transgender women, the Endocrine Society recommends that these patients follow the same screening guidelines as cisgender women.4,6
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Wierckx K et al. J Sex Med. 2014;11(5):1240-7.
2. Mehra G et al. Plast Reconstr Surg Glob Open 2021 Jan 21;9(1):e3362. doi: 10.1097/GOX.0000000000003362.
3. Schecter LS, Schechter RB. Breast and chest surgery for transgender patients. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier, 2020:73-81.
4. Colebunders B et al. Top surgery. In: Salgado CJ et al. ed. Gender Affirmation: Medical and Surgical Perspectives. New York, NY: Thieme, 2017:51-66.
5. De Boer M et al. Aesthet Surg J. 2017;37:NP83-NP87.
6. Coon D et al. Plast Reconstr Surg. 2020 Jun;145(6):1343-53.
7. Kanhai RC et al. Br J Plast Surg. 2000;53:209-11.
Augmentation mammaplasty, otherwise known as a breast augmentation, is one of the most common cosmetic procedures performed in cisgender females. Gynecologists routinely perform annual breast examinations and order screening mammography in cisgender women with breast implants. Similarly, there is an increasing number of transgender women seeking breast augmentation – with approximately 60%-70% of patients having desired or undergone the procedure.1 Consequently, these patients are instructed by their surgeons to follow up with gynecologists for annual examinations and screening. While there are many similarities in technique and procedure, there are nuances in patient demographics, anatomy, and surgical technique that obstetricians/gynecologists should be aware of when examining these patients or prior to referring them to a surgeon for augmentation.2
Many patients who are dissatisfied with breast size from hormone therapy alone will seek out augmentation mammaplasty. In patients taking estrogen for hormone therapy, breast growth will commence around 2-3 months and peak over 1-2 years.3 Unlike chest surgery for transmasculine individuals, it is recommended that transfeminine patients seeking breast augmentation wait a minimum of 12 months before to surgery to allow for maximum breast enlargement. As with breast growth in cisgender females, the extent of breast development is multifactorial and varies from individual to individual. Current literature does not suggest that estrogen type or dose affects the ultimate breast size; however, younger age, tissue sensitivity, and body weight may affect breast volume.3 Referral to a genetic counselor and preoperative imaging may be necessary if a patient has a history concerning for a genetic or familial predisposition to breast cancer.
Implant selection and placement is determined by a variety of factors. While the overall principles of augmentation mammaplasty are essentially the same, there are anatomic differences in transfeminine patients that surgeons must take into consideration at the time of the consultation and during the surgery itself. For example, the pectoralis major muscle is more defined, there is a longer sternal notch-to-nipple distance, the chest wall is broader and more barrel-shaped, and there is a shorter distance between the nipple and the inframammary crease.2-4 As a result of the broader chest wall, it is extremely difficult to achieve central cleavage even with larger implant selection. The surgeon must also ensure that the nipple and areola overlie the implant centrally. Medial placement of the implant will result in lateral displacement of the nipples, which can have an unsatisfactory cosmetic appearance.
Incision location can be axillary, inframammary, or even transareolar, although the latter is less common due to the smaller areolar size and larger implant choice.3 If the inframammary incision is used, it should be placed lower than the natural inframammary fold because the distance between the inferior areolar margin and inframammary fold is shorter and will expand after the implant is placed.4 While both saline and silicone implants are available, many surgeons (myself included), favor more form-stable silicone implants. Given the association between anaplastic large-cell lymphoma and textured implants, many surgeons also use nontextured, or smooth, cohesive gel silicone implants.5
Pocket selection of the implant itself can be subglandular – directly under the breast mound – or subpectoral – behind the pectoralis muscle. For patients with a pinch test of greater than 1.5 cm (outside of the area of the breast bud), good skin softening, and marked pectoralis hypertrophy, subglandular placement is reasonable.6 In thin patients with minimal breast development, subglandular placement can result in a “double-mound” appearance and can lead to visible implant edges on the periphery.6 Use of the subpectoral plane is more common and is associated with less implant visibility due to an increased amount of soft-tissue coverage and has lower rates of capsular contracture.4 However, due to the more robust pectoralis muscle in transfeminine patients, implant displacement can occur more frequently compared to subglandular placement. The surgeon and patient must have a thorough discussion about the location of the incision, implant material, and pocket placement along with the benefits and complications of the surgical plan.
Complications of augmentation mammaplasty are rare. However, when they occur it can include capsular contracture, breast asymmetry, hematoma formation, loss of nipple sensation, implant malposition, implant displacement below the inframammary crease, implant rupture, and need for revisional surgery.7 If an obstetrician/gynecologist observes any of the aforementioned findings in a postoperative patient, consultation and referral to a plastic surgeon is imperative.
Postoperative assessment and screening are mandatory in all patients who undergo breast augmentation. It is important for the gynecologist to note the incision placement, know the type of implant used (saline or silicone), and delineate where the implant was placed. If silicone implants are used, breast MRI is more sensitive in detecting implant rupture compared to mammography alone. Given the relatively poor epidemiologic data on breast cancer in transgender women, the Endocrine Society recommends that these patients follow the same screening guidelines as cisgender women.4,6
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Wierckx K et al. J Sex Med. 2014;11(5):1240-7.
2. Mehra G et al. Plast Reconstr Surg Glob Open 2021 Jan 21;9(1):e3362. doi: 10.1097/GOX.0000000000003362.
3. Schecter LS, Schechter RB. Breast and chest surgery for transgender patients. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier, 2020:73-81.
4. Colebunders B et al. Top surgery. In: Salgado CJ et al. ed. Gender Affirmation: Medical and Surgical Perspectives. New York, NY: Thieme, 2017:51-66.
5. De Boer M et al. Aesthet Surg J. 2017;37:NP83-NP87.
6. Coon D et al. Plast Reconstr Surg. 2020 Jun;145(6):1343-53.
7. Kanhai RC et al. Br J Plast Surg. 2000;53:209-11.
Augmentation mammaplasty, otherwise known as a breast augmentation, is one of the most common cosmetic procedures performed in cisgender females. Gynecologists routinely perform annual breast examinations and order screening mammography in cisgender women with breast implants. Similarly, there is an increasing number of transgender women seeking breast augmentation – with approximately 60%-70% of patients having desired or undergone the procedure.1 Consequently, these patients are instructed by their surgeons to follow up with gynecologists for annual examinations and screening. While there are many similarities in technique and procedure, there are nuances in patient demographics, anatomy, and surgical technique that obstetricians/gynecologists should be aware of when examining these patients or prior to referring them to a surgeon for augmentation.2
Many patients who are dissatisfied with breast size from hormone therapy alone will seek out augmentation mammaplasty. In patients taking estrogen for hormone therapy, breast growth will commence around 2-3 months and peak over 1-2 years.3 Unlike chest surgery for transmasculine individuals, it is recommended that transfeminine patients seeking breast augmentation wait a minimum of 12 months before to surgery to allow for maximum breast enlargement. As with breast growth in cisgender females, the extent of breast development is multifactorial and varies from individual to individual. Current literature does not suggest that estrogen type or dose affects the ultimate breast size; however, younger age, tissue sensitivity, and body weight may affect breast volume.3 Referral to a genetic counselor and preoperative imaging may be necessary if a patient has a history concerning for a genetic or familial predisposition to breast cancer.
Implant selection and placement is determined by a variety of factors. While the overall principles of augmentation mammaplasty are essentially the same, there are anatomic differences in transfeminine patients that surgeons must take into consideration at the time of the consultation and during the surgery itself. For example, the pectoralis major muscle is more defined, there is a longer sternal notch-to-nipple distance, the chest wall is broader and more barrel-shaped, and there is a shorter distance between the nipple and the inframammary crease.2-4 As a result of the broader chest wall, it is extremely difficult to achieve central cleavage even with larger implant selection. The surgeon must also ensure that the nipple and areola overlie the implant centrally. Medial placement of the implant will result in lateral displacement of the nipples, which can have an unsatisfactory cosmetic appearance.
Incision location can be axillary, inframammary, or even transareolar, although the latter is less common due to the smaller areolar size and larger implant choice.3 If the inframammary incision is used, it should be placed lower than the natural inframammary fold because the distance between the inferior areolar margin and inframammary fold is shorter and will expand after the implant is placed.4 While both saline and silicone implants are available, many surgeons (myself included), favor more form-stable silicone implants. Given the association between anaplastic large-cell lymphoma and textured implants, many surgeons also use nontextured, or smooth, cohesive gel silicone implants.5
Pocket selection of the implant itself can be subglandular – directly under the breast mound – or subpectoral – behind the pectoralis muscle. For patients with a pinch test of greater than 1.5 cm (outside of the area of the breast bud), good skin softening, and marked pectoralis hypertrophy, subglandular placement is reasonable.6 In thin patients with minimal breast development, subglandular placement can result in a “double-mound” appearance and can lead to visible implant edges on the periphery.6 Use of the subpectoral plane is more common and is associated with less implant visibility due to an increased amount of soft-tissue coverage and has lower rates of capsular contracture.4 However, due to the more robust pectoralis muscle in transfeminine patients, implant displacement can occur more frequently compared to subglandular placement. The surgeon and patient must have a thorough discussion about the location of the incision, implant material, and pocket placement along with the benefits and complications of the surgical plan.
Complications of augmentation mammaplasty are rare. However, when they occur it can include capsular contracture, breast asymmetry, hematoma formation, loss of nipple sensation, implant malposition, implant displacement below the inframammary crease, implant rupture, and need for revisional surgery.7 If an obstetrician/gynecologist observes any of the aforementioned findings in a postoperative patient, consultation and referral to a plastic surgeon is imperative.
Postoperative assessment and screening are mandatory in all patients who undergo breast augmentation. It is important for the gynecologist to note the incision placement, know the type of implant used (saline or silicone), and delineate where the implant was placed. If silicone implants are used, breast MRI is more sensitive in detecting implant rupture compared to mammography alone. Given the relatively poor epidemiologic data on breast cancer in transgender women, the Endocrine Society recommends that these patients follow the same screening guidelines as cisgender women.4,6
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Wierckx K et al. J Sex Med. 2014;11(5):1240-7.
2. Mehra G et al. Plast Reconstr Surg Glob Open 2021 Jan 21;9(1):e3362. doi: 10.1097/GOX.0000000000003362.
3. Schecter LS, Schechter RB. Breast and chest surgery for transgender patients. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier, 2020:73-81.
4. Colebunders B et al. Top surgery. In: Salgado CJ et al. ed. Gender Affirmation: Medical and Surgical Perspectives. New York, NY: Thieme, 2017:51-66.
5. De Boer M et al. Aesthet Surg J. 2017;37:NP83-NP87.
6. Coon D et al. Plast Reconstr Surg. 2020 Jun;145(6):1343-53.
7. Kanhai RC et al. Br J Plast Surg. 2000;53:209-11.
Do personality traits predict cognitive decline?
new research shows.
Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.
Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.
Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.
“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.
“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.
The study was published online in the Journal of Personality and Social Psychology.
Competing risk factors
Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.
“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.
Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”
Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”
For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.
To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
Cognitive healthspan
By the end of the study, over half of the sample (54%) had died.
Most transitions showed “relative stability in cognitive status across measurement occasions.”
- NCI to NCI (n = 7,368)
- MCI to MCI (n = 1,244)
- Dementia to dementia (n = 876)
There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.
There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”
After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.
Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).
Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.
Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.
“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.
Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.
In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.
The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.
Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
‘Invaluable window’
In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”
“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.
Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.
Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”
The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.
Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.
Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.
“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.
“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.
The study was published online in the Journal of Personality and Social Psychology.
Competing risk factors
Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.
“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.
Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”
Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”
For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.
To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
Cognitive healthspan
By the end of the study, over half of the sample (54%) had died.
Most transitions showed “relative stability in cognitive status across measurement occasions.”
- NCI to NCI (n = 7,368)
- MCI to MCI (n = 1,244)
- Dementia to dementia (n = 876)
There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.
There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”
After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.
Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).
Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.
Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.
“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.
Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.
In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.
The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.
Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
‘Invaluable window’
In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”
“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.
Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.
Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”
The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.
Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.
Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.
“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.
“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.
The study was published online in the Journal of Personality and Social Psychology.
Competing risk factors
Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.
“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.
Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”
Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”
For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.
To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
Cognitive healthspan
By the end of the study, over half of the sample (54%) had died.
Most transitions showed “relative stability in cognitive status across measurement occasions.”
- NCI to NCI (n = 7,368)
- MCI to MCI (n = 1,244)
- Dementia to dementia (n = 876)
There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.
There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”
After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.
Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).
Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.
Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.
“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.
Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.
In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.
The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.
Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
‘Invaluable window’
In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”
“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.
Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.
Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”
The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
Black, senior patients more likely to get unneeded antibiotics
Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.
Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.
Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.
The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.
Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.
“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.
Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”
The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.
Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.
When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.
Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.
“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”
“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”
For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.
For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.
“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”
Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.
“We need more information on what drives this in older adults,” she said.
A version of this article first appeared on Medscape.com.
Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.
Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.
Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.
The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.
Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.
“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.
Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”
The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.
Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.
When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.
Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.
“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”
“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”
For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.
For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.
“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”
Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.
“We need more information on what drives this in older adults,” she said.
A version of this article first appeared on Medscape.com.
Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.
Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.
Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.
The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.
Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.
“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.
Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”
The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.
Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.
When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.
Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.
“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”
“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”
For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.
For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.
“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”
Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.
“We need more information on what drives this in older adults,” she said.
A version of this article first appeared on Medscape.com.
Doc accused of killing 14 patients found not guilty
In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.
The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.
In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.
The prosecutors in the case declined to comment, other than to say they “accept” the verdict.
Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.
The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.
To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.
“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”
The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.
“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”
Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.
Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.
Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.
“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”
The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.
“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”
There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.
Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.
Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”
Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.
The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.
In 2019, the Centers for Medicare & Medicaid Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.
Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.
During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.
Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.
Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.
The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”
At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.
Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.
Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.
“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”
Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.
In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.
Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however.
“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.
There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.
In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.
But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”
During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.
Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.
A version of this article first appeared on Medscape.com.
In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.
The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.
In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.
The prosecutors in the case declined to comment, other than to say they “accept” the verdict.
Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.
The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.
To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.
“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”
The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.
“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”
Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.
Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.
Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.
“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”
The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.
“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”
There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.
Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.
Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”
Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.
The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.
In 2019, the Centers for Medicare & Medicaid Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.
Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.
During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.
Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.
Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.
The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”
At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.
Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.
Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.
“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”
Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.
In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.
Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however.
“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.
There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.
In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.
But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”
During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.
Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.
A version of this article first appeared on Medscape.com.
In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.
The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.
In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.
The prosecutors in the case declined to comment, other than to say they “accept” the verdict.
Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.
The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.
To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.
“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”
The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.
“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”
Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.
Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.
Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.
“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”
The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.
“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”
There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.
Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.
Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”
Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.
The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.
In 2019, the Centers for Medicare & Medicaid Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.
Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.
During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.
Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.
Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.
The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”
At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.
Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.
Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.
“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”
Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.
In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.
Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however.
“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.
There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.
In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.
But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”
During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.
Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.
A version of this article first appeared on Medscape.com.
Alcohol dependence drug the next antianxiety med?
, early research suggests.
Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.
Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.
“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.
The study was published online in Frontiers in Pharmacology.
Inhibitory function
Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.
In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.
“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.
The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.
The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.
Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.
Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).
A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).
Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).
Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).
In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.
The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.
In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.
Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.
“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
Humanity’s most common affliction
Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”
Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”
Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”
Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”
Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”
He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”
However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.
The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.
A version of this article first appeared on Medscape.com.
, early research suggests.
Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.
Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.
“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.
The study was published online in Frontiers in Pharmacology.
Inhibitory function
Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.
In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.
“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.
The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.
The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.
Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.
Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).
A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).
Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).
Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).
In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.
The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.
In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.
Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.
“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
Humanity’s most common affliction
Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”
Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”
Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”
Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”
Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”
He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”
However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.
The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.
A version of this article first appeared on Medscape.com.
, early research suggests.
Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.
Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.
“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.
The study was published online in Frontiers in Pharmacology.
Inhibitory function
Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.
In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.
“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.
The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.
The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.
Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.
Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).
A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).
Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).
Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).
In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.
The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.
In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.
Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.
“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
Humanity’s most common affliction
Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”
Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”
Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”
Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”
Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”
He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”
However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.
The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN PHARMACOLOGY
COVID-19 accelerated psychological problems for critical care clinicians
Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.
The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.
The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.
To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).
Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.
Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.
Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.
The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.
The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.
Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”
The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.
Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”
The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.
As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.
The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.
The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.
The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.
To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).
Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.
Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.
Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.
The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.
The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.
Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”
The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.
Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”
The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.
As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.
The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.
The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.
The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.
To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).
Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.
Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.
Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.
The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.
The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.
Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”
The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.
Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”
The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.
As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.
The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SCCM 2022
Abdominal cramping and diarrhea
On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up.
On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case.
Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.
UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.
Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse.
To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up.
On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case.
Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.
UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.
Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse.
To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up.
On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case.
Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.
UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.
Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse.
To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.
Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX
Bhupinder S. Anand, MD, has disclosed no relevant financial relationships
A 46-year-old man presents with abdominal cramping and diarrhea and reports about five bowel movements per day for the past 2 weeks. Height is 5 ft 9 in and weight is 157 lb (BMI, 23.2). History is significant for ulcerative colitis (UC), diagnosed about 20 years ago with proctitis and having progressed about 8 years ago to left-sided disease. He smoked "lightly" through his 20s. Until about a month ago, the patient had been able to maintain remission with oral 5-aminosalicylic acid (ASA) therapy (2 g/d). Endoscopy shows granularity and friability of the mucosa with the inflamed segment extending proximal to the splenic flexure, though there is patchiness of the histologic activity. Colonoscopy rules out distal ileal involvement. Stool culture is negative.
