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Childhood trauma may influence vaccine hesitancy
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, data published Feb. 1 suggest.
The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.
The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.
The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.
For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.
Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.
However, he said, the association they found may have key messages for clinicians.
“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
More trauma, less trust
The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.
The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.
It also included personal details and long-term health information.
About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.
According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.
They also investigated measures of trust and preference for different health regulations.
People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.
“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.
People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.
People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions.
“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.
He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.
It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
Loss of control
“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.
She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.
Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.
Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.
She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
Young adults of particular concern
The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.
The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.
“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”
This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN
Intervention in Acute Hospital Unit Reduces Delirium Incidence for Older Adults, Has No Effect on Length of Stay, Other Complications
Study Overview
Objective: To examine the effect of the intervention “Eat Walk Engage,” a program that is designed to more consistently deliver age-friendly principles of care to older individuals in acute medical and surgical wards.
Design: This cluster randomized trial to examine the effect of an intervention in acute medical and surgical wards on older adults was conducted in 8 acute medical and surgical wards in 4 public hospitals in Australia from 2016 to 2017. To be eligible to participate in this trial, wards had to have the following: a patient population with 50% of patients aged 65 years and older; perceived alignment with hospital priorities; and nurse manager agreement to participation. Randomization was stratified by hospital, resulting in 4 wards with the intervention (a general medicine ward, an orthopedic ward, a general surgery ward, and a respiratory medicine ward) and 4 control wards (2 general medicine wards, a respiratory medicine ward, and a general surgery ward). Participants were consecutive inpatients aged 65 years or older who were admitted to the ward for at least 3 consecutive days during the study time period. Exclusion criteria included terminal or critical illness, severe cognitive impairment without a surrogate decision-maker, non-English speaking, or previously enrolled in the trial. Of a total of 453 patients who were eligible from the intervention wards, 188 were excluded and 6 died, yielding 259 participants in the intervention group. There were 413 patients eligible from the control wards, with 139 excluded and 3 deaths, yielding 271 participants in the control group.
Intervention: The intervention, called “Eat Walk Engage,” was developed to target older adults at risk for hospital-associated complications of delirium, functional decline, pressure injuries, falls, and incontinence, and aimed to improve care practices, environment, and culture to support age-friendly principles. This ward-based program delivered a structured improvement intervention through a site facilitator who is a nurse or allied health professional. The site facilitator identified opportunities for improvement using structured assessments of context, patient-experience interviews, and audits of care processes, and engaged an interdisciplinary working group from the intervention wards to participate in an hour-per-month meeting to develop plans for iterative improvements. Each site developed their own intervention plan; examples of interventions include shifting priorities to enable staff to increase the proportion of patients sitting in a chair for meals; designating the patient lounge as a walking destination to increase the proportion of time patients spend mobile; and using orientation boards and small groups to engage older patients in meaningful activities.
Main outcome measures: Study outcome measures included hospital-associated complications for older people, which is a composite of hospital-associated delirium, hospital-associated disability, hospital-associated incontinence, and fall or pressure injury during hospitalization. Delirium was assessed using the 3-minute diagnostic interview for Confusion Assessment Method (3D-CAM); hospital-associated disability was defined as new disability at discharge compared to 2 weeks prior to hospitalization. The primary outcome was defined as incidence of any complications and hospital length of stay. Secondary outcomes included incidence of individual complications, hospital discharge to facility, mortality at 6 months, and readmission for any cause at 6 months.
Main results: Patient characteristics for the intervention and control groups, respectively, were: 47% women with a mean age of 75.9 years (SD, 7.3), and 53% women with a mean age of 78.0 years (SD, 8.2). For the primary outcome, 46.4% of participants in the intervention group experienced any hospital complications compared with 51.8% in the control group (odds ratio [OR], 1.07; 95% CI, 0.71-1.61). The incidence of delirium was lower in the intervention group as compared with the control group (15.9% vs 31.4%; OR, 0.53; 95% CI, 0.31-0.90), while there were no other differences in the incidence rates of other complications. There was also no difference in hospital length of stay; median length of stay in the intervention group was 6 days (interquartile range [IQR], 4-9 days) compared with 7 days in the control group (IQR, 5-10), with an estimated mean difference in length of stay of 0.16 days (95% CI, –0.43 to 0.78 days). There was also no significant difference in mortality or all-cause readmission at 6 months.
Conclusion: The intervention “Eat Walk Engage” did not reduce hospital-associated complications overall or hospital length of stay, but it did reduce the incidence of hospital-associated delirium.
Commentary
Older adults, often with reduced physiologic reserve, when admitted to the hospital with an acute illness may be vulnerable to potential hazards of hospitalization, such as complications from prolonged periods of immobility, pressure injury, and delirium.1 Models of care in the inpatient setting to reduce these hazards, including the Acute Care for the Elderly model and the Mobile Acute Care for the Elderly Team model, have been examined in clinical trials.2,3 Specifically, models of care to prevent and treat delirium have been developed and tested over the past decade.4 The effect of these models in improving function, reducing complications, and reducing delirium incidence has been well documented. The present study adds to the literature by testing a model that utilizes implementation science methods to take into account real-world settings. In contrast with prior models-of-care studies, the implementation of the intervention at each ward was not prescriptive, but rather was developed in each ward in an iterative manner with stakeholder input. The advantage of this approach is that engagement of stakeholders at each intervention ward obtains buy-in from staff, mobilizing staff in a way that a prescriptive model of care may not; this ultimately may lead to longer-lasting change. The iterative approach also allows for the intervention to be adapted to conditions and settings over time. Other studies have taken this approach of using implementation science to drive change.5 Although the intervention in the present study failed to improve the primary outcome, it did reduce the incidence of delirium, which is a significant outcome and one that may confer considerable benefits to older adults under the model’s care.
A limitation of the intervention’s nonprescriptive approach is that, because of the variation of the interventions across sites, it is difficult to discern what elements drove the clinical outcomes. In addition, it would be challenging to consider what aspects of the intervention did not work should refinement or changes be needed. How one may measure fidelity to the intervention or how well a site implements the intervention and its relationship with clinical outcomes will need to be examined further.
Application for Clinical Practice
Clinicians look to effective models of care to improve clinical outcomes for older adults in the hospital. The intervention described in this study offers a real-world approach that may need less upfront investment than other recently studied models, such as the Acute Care for the Elderly model, which requires structural and staffing enhancements. Clinicians and health system leaders may consider implementing this model to improve the care delivered to older adults in the hospital as it may help reduce the incidence of delirium among the older adults they serve.
–William W. Hung, MD, MPH
Disclosures: None.
1. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118(3):219-223. doi:10.7326/0003-4819-118-3-199302010-00011
2. Fox MT, Persaud M, Maimets I, et al. Effectiveness of acute geriatric unit care using acute care for elders components: a systematic review and meta-analysis. J Am Geriatr Soc. 2012;60(12):2237-2245. doi:10.1111/jgs.12028
3. Hung WW, Ross JS, Farber J, Siu AL. Evaluation of the Mobile Acute Care of the Elderly (MACE) service. JAMA Intern Med. 2013;173(11):990-996. doi:10.1001/jamainternmed.2013.478
4. Hshieh TT, Yang T, Gartaganis SL, Yue J, Inouye SK. Hospital Elder Life Program: systematic review and meta-analysis of effectiveness. Am J Geriatr Psychiatry. 2018;26(10):1015-1033. doi:10.1016/j.jagp.2018.06.007
5. Naughton C, Cummins H, de Foubert M, et al. Implementation of the Frailty Care Bundle (FCB) to promote mobilisation, nutrition and cognitive engagement in older people in acute care settings: protocol for an implementation science study. [version 1; peer review: 1 approved]. HRB Open Res. 2022;5:3. doi:10.12688/hrbopenres.134731
Study Overview
Objective: To examine the effect of the intervention “Eat Walk Engage,” a program that is designed to more consistently deliver age-friendly principles of care to older individuals in acute medical and surgical wards.
Design: This cluster randomized trial to examine the effect of an intervention in acute medical and surgical wards on older adults was conducted in 8 acute medical and surgical wards in 4 public hospitals in Australia from 2016 to 2017. To be eligible to participate in this trial, wards had to have the following: a patient population with 50% of patients aged 65 years and older; perceived alignment with hospital priorities; and nurse manager agreement to participation. Randomization was stratified by hospital, resulting in 4 wards with the intervention (a general medicine ward, an orthopedic ward, a general surgery ward, and a respiratory medicine ward) and 4 control wards (2 general medicine wards, a respiratory medicine ward, and a general surgery ward). Participants were consecutive inpatients aged 65 years or older who were admitted to the ward for at least 3 consecutive days during the study time period. Exclusion criteria included terminal or critical illness, severe cognitive impairment without a surrogate decision-maker, non-English speaking, or previously enrolled in the trial. Of a total of 453 patients who were eligible from the intervention wards, 188 were excluded and 6 died, yielding 259 participants in the intervention group. There were 413 patients eligible from the control wards, with 139 excluded and 3 deaths, yielding 271 participants in the control group.
Intervention: The intervention, called “Eat Walk Engage,” was developed to target older adults at risk for hospital-associated complications of delirium, functional decline, pressure injuries, falls, and incontinence, and aimed to improve care practices, environment, and culture to support age-friendly principles. This ward-based program delivered a structured improvement intervention through a site facilitator who is a nurse or allied health professional. The site facilitator identified opportunities for improvement using structured assessments of context, patient-experience interviews, and audits of care processes, and engaged an interdisciplinary working group from the intervention wards to participate in an hour-per-month meeting to develop plans for iterative improvements. Each site developed their own intervention plan; examples of interventions include shifting priorities to enable staff to increase the proportion of patients sitting in a chair for meals; designating the patient lounge as a walking destination to increase the proportion of time patients spend mobile; and using orientation boards and small groups to engage older patients in meaningful activities.
Main outcome measures: Study outcome measures included hospital-associated complications for older people, which is a composite of hospital-associated delirium, hospital-associated disability, hospital-associated incontinence, and fall or pressure injury during hospitalization. Delirium was assessed using the 3-minute diagnostic interview for Confusion Assessment Method (3D-CAM); hospital-associated disability was defined as new disability at discharge compared to 2 weeks prior to hospitalization. The primary outcome was defined as incidence of any complications and hospital length of stay. Secondary outcomes included incidence of individual complications, hospital discharge to facility, mortality at 6 months, and readmission for any cause at 6 months.
Main results: Patient characteristics for the intervention and control groups, respectively, were: 47% women with a mean age of 75.9 years (SD, 7.3), and 53% women with a mean age of 78.0 years (SD, 8.2). For the primary outcome, 46.4% of participants in the intervention group experienced any hospital complications compared with 51.8% in the control group (odds ratio [OR], 1.07; 95% CI, 0.71-1.61). The incidence of delirium was lower in the intervention group as compared with the control group (15.9% vs 31.4%; OR, 0.53; 95% CI, 0.31-0.90), while there were no other differences in the incidence rates of other complications. There was also no difference in hospital length of stay; median length of stay in the intervention group was 6 days (interquartile range [IQR], 4-9 days) compared with 7 days in the control group (IQR, 5-10), with an estimated mean difference in length of stay of 0.16 days (95% CI, –0.43 to 0.78 days). There was also no significant difference in mortality or all-cause readmission at 6 months.
Conclusion: The intervention “Eat Walk Engage” did not reduce hospital-associated complications overall or hospital length of stay, but it did reduce the incidence of hospital-associated delirium.
Commentary
Older adults, often with reduced physiologic reserve, when admitted to the hospital with an acute illness may be vulnerable to potential hazards of hospitalization, such as complications from prolonged periods of immobility, pressure injury, and delirium.1 Models of care in the inpatient setting to reduce these hazards, including the Acute Care for the Elderly model and the Mobile Acute Care for the Elderly Team model, have been examined in clinical trials.2,3 Specifically, models of care to prevent and treat delirium have been developed and tested over the past decade.4 The effect of these models in improving function, reducing complications, and reducing delirium incidence has been well documented. The present study adds to the literature by testing a model that utilizes implementation science methods to take into account real-world settings. In contrast with prior models-of-care studies, the implementation of the intervention at each ward was not prescriptive, but rather was developed in each ward in an iterative manner with stakeholder input. The advantage of this approach is that engagement of stakeholders at each intervention ward obtains buy-in from staff, mobilizing staff in a way that a prescriptive model of care may not; this ultimately may lead to longer-lasting change. The iterative approach also allows for the intervention to be adapted to conditions and settings over time. Other studies have taken this approach of using implementation science to drive change.5 Although the intervention in the present study failed to improve the primary outcome, it did reduce the incidence of delirium, which is a significant outcome and one that may confer considerable benefits to older adults under the model’s care.
A limitation of the intervention’s nonprescriptive approach is that, because of the variation of the interventions across sites, it is difficult to discern what elements drove the clinical outcomes. In addition, it would be challenging to consider what aspects of the intervention did not work should refinement or changes be needed. How one may measure fidelity to the intervention or how well a site implements the intervention and its relationship with clinical outcomes will need to be examined further.
Application for Clinical Practice
Clinicians look to effective models of care to improve clinical outcomes for older adults in the hospital. The intervention described in this study offers a real-world approach that may need less upfront investment than other recently studied models, such as the Acute Care for the Elderly model, which requires structural and staffing enhancements. Clinicians and health system leaders may consider implementing this model to improve the care delivered to older adults in the hospital as it may help reduce the incidence of delirium among the older adults they serve.
–William W. Hung, MD, MPH
Disclosures: None.
Study Overview
Objective: To examine the effect of the intervention “Eat Walk Engage,” a program that is designed to more consistently deliver age-friendly principles of care to older individuals in acute medical and surgical wards.
Design: This cluster randomized trial to examine the effect of an intervention in acute medical and surgical wards on older adults was conducted in 8 acute medical and surgical wards in 4 public hospitals in Australia from 2016 to 2017. To be eligible to participate in this trial, wards had to have the following: a patient population with 50% of patients aged 65 years and older; perceived alignment with hospital priorities; and nurse manager agreement to participation. Randomization was stratified by hospital, resulting in 4 wards with the intervention (a general medicine ward, an orthopedic ward, a general surgery ward, and a respiratory medicine ward) and 4 control wards (2 general medicine wards, a respiratory medicine ward, and a general surgery ward). Participants were consecutive inpatients aged 65 years or older who were admitted to the ward for at least 3 consecutive days during the study time period. Exclusion criteria included terminal or critical illness, severe cognitive impairment without a surrogate decision-maker, non-English speaking, or previously enrolled in the trial. Of a total of 453 patients who were eligible from the intervention wards, 188 were excluded and 6 died, yielding 259 participants in the intervention group. There were 413 patients eligible from the control wards, with 139 excluded and 3 deaths, yielding 271 participants in the control group.
Intervention: The intervention, called “Eat Walk Engage,” was developed to target older adults at risk for hospital-associated complications of delirium, functional decline, pressure injuries, falls, and incontinence, and aimed to improve care practices, environment, and culture to support age-friendly principles. This ward-based program delivered a structured improvement intervention through a site facilitator who is a nurse or allied health professional. The site facilitator identified opportunities for improvement using structured assessments of context, patient-experience interviews, and audits of care processes, and engaged an interdisciplinary working group from the intervention wards to participate in an hour-per-month meeting to develop plans for iterative improvements. Each site developed their own intervention plan; examples of interventions include shifting priorities to enable staff to increase the proportion of patients sitting in a chair for meals; designating the patient lounge as a walking destination to increase the proportion of time patients spend mobile; and using orientation boards and small groups to engage older patients in meaningful activities.
Main outcome measures: Study outcome measures included hospital-associated complications for older people, which is a composite of hospital-associated delirium, hospital-associated disability, hospital-associated incontinence, and fall or pressure injury during hospitalization. Delirium was assessed using the 3-minute diagnostic interview for Confusion Assessment Method (3D-CAM); hospital-associated disability was defined as new disability at discharge compared to 2 weeks prior to hospitalization. The primary outcome was defined as incidence of any complications and hospital length of stay. Secondary outcomes included incidence of individual complications, hospital discharge to facility, mortality at 6 months, and readmission for any cause at 6 months.
Main results: Patient characteristics for the intervention and control groups, respectively, were: 47% women with a mean age of 75.9 years (SD, 7.3), and 53% women with a mean age of 78.0 years (SD, 8.2). For the primary outcome, 46.4% of participants in the intervention group experienced any hospital complications compared with 51.8% in the control group (odds ratio [OR], 1.07; 95% CI, 0.71-1.61). The incidence of delirium was lower in the intervention group as compared with the control group (15.9% vs 31.4%; OR, 0.53; 95% CI, 0.31-0.90), while there were no other differences in the incidence rates of other complications. There was also no difference in hospital length of stay; median length of stay in the intervention group was 6 days (interquartile range [IQR], 4-9 days) compared with 7 days in the control group (IQR, 5-10), with an estimated mean difference in length of stay of 0.16 days (95% CI, –0.43 to 0.78 days). There was also no significant difference in mortality or all-cause readmission at 6 months.
Conclusion: The intervention “Eat Walk Engage” did not reduce hospital-associated complications overall or hospital length of stay, but it did reduce the incidence of hospital-associated delirium.
Commentary
Older adults, often with reduced physiologic reserve, when admitted to the hospital with an acute illness may be vulnerable to potential hazards of hospitalization, such as complications from prolonged periods of immobility, pressure injury, and delirium.1 Models of care in the inpatient setting to reduce these hazards, including the Acute Care for the Elderly model and the Mobile Acute Care for the Elderly Team model, have been examined in clinical trials.2,3 Specifically, models of care to prevent and treat delirium have been developed and tested over the past decade.4 The effect of these models in improving function, reducing complications, and reducing delirium incidence has been well documented. The present study adds to the literature by testing a model that utilizes implementation science methods to take into account real-world settings. In contrast with prior models-of-care studies, the implementation of the intervention at each ward was not prescriptive, but rather was developed in each ward in an iterative manner with stakeholder input. The advantage of this approach is that engagement of stakeholders at each intervention ward obtains buy-in from staff, mobilizing staff in a way that a prescriptive model of care may not; this ultimately may lead to longer-lasting change. The iterative approach also allows for the intervention to be adapted to conditions and settings over time. Other studies have taken this approach of using implementation science to drive change.5 Although the intervention in the present study failed to improve the primary outcome, it did reduce the incidence of delirium, which is a significant outcome and one that may confer considerable benefits to older adults under the model’s care.
A limitation of the intervention’s nonprescriptive approach is that, because of the variation of the interventions across sites, it is difficult to discern what elements drove the clinical outcomes. In addition, it would be challenging to consider what aspects of the intervention did not work should refinement or changes be needed. How one may measure fidelity to the intervention or how well a site implements the intervention and its relationship with clinical outcomes will need to be examined further.
Application for Clinical Practice
Clinicians look to effective models of care to improve clinical outcomes for older adults in the hospital. The intervention described in this study offers a real-world approach that may need less upfront investment than other recently studied models, such as the Acute Care for the Elderly model, which requires structural and staffing enhancements. Clinicians and health system leaders may consider implementing this model to improve the care delivered to older adults in the hospital as it may help reduce the incidence of delirium among the older adults they serve.
–William W. Hung, MD, MPH
Disclosures: None.
1. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118(3):219-223. doi:10.7326/0003-4819-118-3-199302010-00011
2. Fox MT, Persaud M, Maimets I, et al. Effectiveness of acute geriatric unit care using acute care for elders components: a systematic review and meta-analysis. J Am Geriatr Soc. 2012;60(12):2237-2245. doi:10.1111/jgs.12028
3. Hung WW, Ross JS, Farber J, Siu AL. Evaluation of the Mobile Acute Care of the Elderly (MACE) service. JAMA Intern Med. 2013;173(11):990-996. doi:10.1001/jamainternmed.2013.478
4. Hshieh TT, Yang T, Gartaganis SL, Yue J, Inouye SK. Hospital Elder Life Program: systematic review and meta-analysis of effectiveness. Am J Geriatr Psychiatry. 2018;26(10):1015-1033. doi:10.1016/j.jagp.2018.06.007
5. Naughton C, Cummins H, de Foubert M, et al. Implementation of the Frailty Care Bundle (FCB) to promote mobilisation, nutrition and cognitive engagement in older people in acute care settings: protocol for an implementation science study. [version 1; peer review: 1 approved]. HRB Open Res. 2022;5:3. doi:10.12688/hrbopenres.134731
1. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118(3):219-223. doi:10.7326/0003-4819-118-3-199302010-00011
2. Fox MT, Persaud M, Maimets I, et al. Effectiveness of acute geriatric unit care using acute care for elders components: a systematic review and meta-analysis. J Am Geriatr Soc. 2012;60(12):2237-2245. doi:10.1111/jgs.12028
3. Hung WW, Ross JS, Farber J, Siu AL. Evaluation of the Mobile Acute Care of the Elderly (MACE) service. JAMA Intern Med. 2013;173(11):990-996. doi:10.1001/jamainternmed.2013.478
4. Hshieh TT, Yang T, Gartaganis SL, Yue J, Inouye SK. Hospital Elder Life Program: systematic review and meta-analysis of effectiveness. Am J Geriatr Psychiatry. 2018;26(10):1015-1033. doi:10.1016/j.jagp.2018.06.007
5. Naughton C, Cummins H, de Foubert M, et al. Implementation of the Frailty Care Bundle (FCB) to promote mobilisation, nutrition and cognitive engagement in older people in acute care settings: protocol for an implementation science study. [version 1; peer review: 1 approved]. HRB Open Res. 2022;5:3. doi:10.12688/hrbopenres.134731
Psychedelic therapy and suicide: A myth busted?
A commonly held belief that classic psychedelic therapy can trigger suicidal thoughts, actions, or other types of self-harm is not supported by research, and, in fact, the opposite may be true.
Results from a meta-analysis of individual patient data showed that psychedelic therapy was associated with large, acute, and sustained decreases in suicidality across a range of clinical patient populations.
“ It gives us a better understanding of the effects of psychedelics on suicidality in the context of clinical trials,” study investigator Cory Weissman, MD, department of psychiatry, University of Toronto, told this news organization.
The evidence suggests psychedelic therapy “may reduce suicidal ideation when administered in the appropriate setting and offered to carefully screened patients,” Dr. Weissman said.
The findings were published online Jan. 18 in The Journal of Clinical Psychiatry.
More research needed
The analysis included seven psychedelic therapy clinical trials that had data on suicidality. Five of the trials used psilocybin plus psychotherapy and two used ayahuasca plus psychotherapy. All seven trials had a “low” risk of bias.
Patients included in the trials had treatment-resistant major depressive disorder (MDD), recurrent MDD, AIDS-related demoralization, and distress related to life-threatening cancer.
The meta-analytic results showed significant decreases in suicidality at all acute time points (80 to 240 minutes post administration) and at most post-acute time points (1 day to 4 months post administration).
Effect sizes for reductions in suicidality were “large” at all acute time points, with standardized mean differences (SMD) ranging from -1.48 to -1.72, and remained large from 1 day to 3-4 months after therapy (SMD range, -1.50 to -2.36).
At 6 months, the effect size for reductions in suicidality with psychedelic therapy was “medium” (SMD, -0.65).
Large effect sizes for reductions in suicidality occurred across the different patient populations represented in the trial, the investigators note.
No study reported any suicide-related adverse events because of administration of a psychedelic. There were also “very few” acute (6.5%) or postacute (3.0%) elevations in suicidality, “providing support for the safety of psychedelic therapy within controlled contexts,” the researchers write.
They caution, however, that large controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality are needed.
Promising avenue
In an accompanying editorial, Daniel Grossman, BS, and Peter Hendricks, PhD, department of health behavior, University of Alabama at Birmingham, note that results of this review warrant “optimism” for use of psychedelics for treatment of suicidality.
Based on this study and others, classic psychedelic therapy for suicidality appears to be a “promising avenue” for further investigation, they write.
However, research and anecdotes about increased suicidality and other self-harm attributed to psychedelic therapy, “though evidently rare, remain a critical concern” for further research to address, Dr. Grossman and Dr. Hendricks add.
The hope is that future research “clarifies who is most subject to these risks, what factors best identify them, and how best to navigate their treatment safely,” they write.
The meta-analysis had no funding. Dr. Weissman receives funding from the Brain and Behavior Research Foundation and serves on the advisory board of GoodCap Pharmaceuticals. Dr. Hendricks is on the scientific advisory board of Bright Minds Biosciences, Eleusis Benefit Corporation, and Rest Pharmaceuticals.
A version of this article first appeared on Medscape.com.
A commonly held belief that classic psychedelic therapy can trigger suicidal thoughts, actions, or other types of self-harm is not supported by research, and, in fact, the opposite may be true.
Results from a meta-analysis of individual patient data showed that psychedelic therapy was associated with large, acute, and sustained decreases in suicidality across a range of clinical patient populations.
“ It gives us a better understanding of the effects of psychedelics on suicidality in the context of clinical trials,” study investigator Cory Weissman, MD, department of psychiatry, University of Toronto, told this news organization.
The evidence suggests psychedelic therapy “may reduce suicidal ideation when administered in the appropriate setting and offered to carefully screened patients,” Dr. Weissman said.
The findings were published online Jan. 18 in The Journal of Clinical Psychiatry.
More research needed
The analysis included seven psychedelic therapy clinical trials that had data on suicidality. Five of the trials used psilocybin plus psychotherapy and two used ayahuasca plus psychotherapy. All seven trials had a “low” risk of bias.
Patients included in the trials had treatment-resistant major depressive disorder (MDD), recurrent MDD, AIDS-related demoralization, and distress related to life-threatening cancer.
The meta-analytic results showed significant decreases in suicidality at all acute time points (80 to 240 minutes post administration) and at most post-acute time points (1 day to 4 months post administration).
Effect sizes for reductions in suicidality were “large” at all acute time points, with standardized mean differences (SMD) ranging from -1.48 to -1.72, and remained large from 1 day to 3-4 months after therapy (SMD range, -1.50 to -2.36).
At 6 months, the effect size for reductions in suicidality with psychedelic therapy was “medium” (SMD, -0.65).
Large effect sizes for reductions in suicidality occurred across the different patient populations represented in the trial, the investigators note.
No study reported any suicide-related adverse events because of administration of a psychedelic. There were also “very few” acute (6.5%) or postacute (3.0%) elevations in suicidality, “providing support for the safety of psychedelic therapy within controlled contexts,” the researchers write.
They caution, however, that large controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality are needed.
Promising avenue
In an accompanying editorial, Daniel Grossman, BS, and Peter Hendricks, PhD, department of health behavior, University of Alabama at Birmingham, note that results of this review warrant “optimism” for use of psychedelics for treatment of suicidality.
Based on this study and others, classic psychedelic therapy for suicidality appears to be a “promising avenue” for further investigation, they write.
However, research and anecdotes about increased suicidality and other self-harm attributed to psychedelic therapy, “though evidently rare, remain a critical concern” for further research to address, Dr. Grossman and Dr. Hendricks add.
The hope is that future research “clarifies who is most subject to these risks, what factors best identify them, and how best to navigate their treatment safely,” they write.
The meta-analysis had no funding. Dr. Weissman receives funding from the Brain and Behavior Research Foundation and serves on the advisory board of GoodCap Pharmaceuticals. Dr. Hendricks is on the scientific advisory board of Bright Minds Biosciences, Eleusis Benefit Corporation, and Rest Pharmaceuticals.
A version of this article first appeared on Medscape.com.
A commonly held belief that classic psychedelic therapy can trigger suicidal thoughts, actions, or other types of self-harm is not supported by research, and, in fact, the opposite may be true.
Results from a meta-analysis of individual patient data showed that psychedelic therapy was associated with large, acute, and sustained decreases in suicidality across a range of clinical patient populations.
“ It gives us a better understanding of the effects of psychedelics on suicidality in the context of clinical trials,” study investigator Cory Weissman, MD, department of psychiatry, University of Toronto, told this news organization.
The evidence suggests psychedelic therapy “may reduce suicidal ideation when administered in the appropriate setting and offered to carefully screened patients,” Dr. Weissman said.
The findings were published online Jan. 18 in The Journal of Clinical Psychiatry.
More research needed
The analysis included seven psychedelic therapy clinical trials that had data on suicidality. Five of the trials used psilocybin plus psychotherapy and two used ayahuasca plus psychotherapy. All seven trials had a “low” risk of bias.
Patients included in the trials had treatment-resistant major depressive disorder (MDD), recurrent MDD, AIDS-related demoralization, and distress related to life-threatening cancer.
The meta-analytic results showed significant decreases in suicidality at all acute time points (80 to 240 minutes post administration) and at most post-acute time points (1 day to 4 months post administration).
Effect sizes for reductions in suicidality were “large” at all acute time points, with standardized mean differences (SMD) ranging from -1.48 to -1.72, and remained large from 1 day to 3-4 months after therapy (SMD range, -1.50 to -2.36).
At 6 months, the effect size for reductions in suicidality with psychedelic therapy was “medium” (SMD, -0.65).
Large effect sizes for reductions in suicidality occurred across the different patient populations represented in the trial, the investigators note.
No study reported any suicide-related adverse events because of administration of a psychedelic. There were also “very few” acute (6.5%) or postacute (3.0%) elevations in suicidality, “providing support for the safety of psychedelic therapy within controlled contexts,” the researchers write.
They caution, however, that large controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality are needed.
Promising avenue
In an accompanying editorial, Daniel Grossman, BS, and Peter Hendricks, PhD, department of health behavior, University of Alabama at Birmingham, note that results of this review warrant “optimism” for use of psychedelics for treatment of suicidality.
Based on this study and others, classic psychedelic therapy for suicidality appears to be a “promising avenue” for further investigation, they write.
However, research and anecdotes about increased suicidality and other self-harm attributed to psychedelic therapy, “though evidently rare, remain a critical concern” for further research to address, Dr. Grossman and Dr. Hendricks add.
The hope is that future research “clarifies who is most subject to these risks, what factors best identify them, and how best to navigate their treatment safely,” they write.
The meta-analysis had no funding. Dr. Weissman receives funding from the Brain and Behavior Research Foundation and serves on the advisory board of GoodCap Pharmaceuticals. Dr. Hendricks is on the scientific advisory board of Bright Minds Biosciences, Eleusis Benefit Corporation, and Rest Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Motherhood and mortality: Navigating miscarriages as a physician
One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there.
“There’s something in there,” she said with a seasoned certainty.
“No there’s not,” I said trying hard to hide any emotion.
“Yes, there is,” she said flatly.
“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room.
My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand.
I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know.
I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation.
Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic.
I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.
I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day.
For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?
So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy.
I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we.
Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen?
I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth.
In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter.
A version of this article first appeared on Medscape.com.
One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there.
“There’s something in there,” she said with a seasoned certainty.
“No there’s not,” I said trying hard to hide any emotion.
“Yes, there is,” she said flatly.
“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room.
My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand.
I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know.
I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation.
Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic.
I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.
I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day.
For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?
So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy.
I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we.
Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen?
I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth.
In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter.
A version of this article first appeared on Medscape.com.
One clinic morning in an office visit, I stood next to the door talking, hand on the doorknob ready to exit. My elderly patient was sitting in the chair next to the door, family member in another, as I attempted my exit. Suddenly, as if looking for something, my patient locked her gaze to my abdomen and began to slowly advance herself forward, eyes squinting for a better view. She had found something. Poke, poke, poke. Three pokes in quick succession into my apparently protruding abdomen stoked an internal horror that I dared not release onto my face. How in the hell could she know? My heart sank – the signs were still there.
“There’s something in there,” she said with a seasoned certainty.
“No there’s not,” I said trying hard to hide any emotion.
“Yes, there is,” she said flatly.
“Grannie, no there isn’t,” her family member interrupted, unknowingly saving me. I thanked them again and quickly left the room.
My patient had the ongoings of slowly progressing dementia. Little did she know she was right. Maybe she had known something in another time and space. Either way, I wasn’t prepared to tell the story. She wasn’t prepared to fully understand.
I tried to forge on to see the next patient. Tears began welling in both eyes. I tilted my head back slightly to prevent the water from falling. I wanted to feel offended, but she couldn’t have known the war my body was fighting at the time. I had not yet shared the pregnancy news with this particular patient, and yet her knowing was telling in a sense. I’m learning that the old folks always know.
I was at work, actively having yet another miscarriage. This was the second of two. This most recent time, we found out at 9 weeks that our baby had stopped growing about a week or so earlier. Cue the denial. Cue the rage. Cue the devastation.
Thinking back, with each pregnancy discovery, we did not wait the customary 3 months before telling anyone. Just about everyone knew. We were immediately excited to start sharing with friends, family, coworkers, and even patients early on. We knew the risks in my 40-something age group but were quintessentially optimistic.
I am a family medicine physician with expert-level knowledge and clinical experiences in women’s health counseling, contraception, conception, and pregnancy. In my training, I’ve delivered babies, been elbow-deep searching for wayward tissue from bleeding uteri, and sutured gaping vaginal lacerations. I’ve cried with new mothers at the end of long labors. I’ve been bear-hugged by doting new fathers. I have an abundance of medical knowledge, and yet the pain and struggle of miscarriage over the past 2.5 years has twice reduced me to absolute pieces. There was no course to teach me how to navigate loss within my own body, no textbook to study so that I could test out of the experience. Life hit us dead-on, and I was broken.
I can say that the experience of a miscarriage does not get easier with each subsequent loss. At least for me, the emotions were always raw and tender. Each one was a new gash to my emotional and physical health. My sanity bled out. I was physically exhausted. The struggles of being a health care worker in the midst of a global pandemic I’m sure did not help the situation. My first miscarriage was just before the start of the pandemic. I was in New York visiting family and after dinner at Tavern on the Green, of all places, when I began showing signs. Two days later, I was at the coffee station in our clinic cafeteria adding my cream and sugar when my ob.gyn.’s office called. The hCG levels were probably too low; a miscarriage was likely. I kept my composure, walked out of the cafeteria, got my car keys, went to my car, and proceeded to scream at the top of my lungs for a few minutes. Afterward, I went back to finish up my work and canceled my clinic for the rest of the day.
For my second miscarriage, I was laying in my doctor’s office getting an ultrasound. I had started bleeding the previous day but thought that the subchorionic hemorrhage noted on the last ultrasound might be the culprit. The bleeding was light. That’s the thing about being a pregnant physician: We know too much. The image on the screen looked abnormal, the remnants a ghost of its former self. I knew something was wrong but held out some hope. She searched and turned and pressed the transducer into my belly for a seemingly better view. She apologized for not finding the heartbeat. How is this happening again?
So how does one get through the loss of multiple pregnancies? I know my husband and I worked hard to get through each loss. We did all the right things a good therapist would recommend: Be present in the moment, go with your feelings, allow yourself to feel everything. There were no wrong emotions. Little by little we grieved and healed, grieved and healed. Having a successful pregnancy did help. Miracles are not promised but I believe we were sent one, and her name is Giavonna Barbara. Bookended by miscarriages, she has made me realize just how precious and delicate life really is. She is our absolute world and joy.
I’ve learned twice now that men mourn differently than women. Not any less, just in a different way. There is a pain in the silence that often goes unvocalized, but it is of no less value. My husband and I allowed each other to heal in our own unique ways, and that has made all of the difference. I think I knew I was doing okay when one day I found something funny and I let out the heartiest laugh my belly could muster. A different purpose was renewed. Tears were harder to come by. Hope for the future again sprung eternal. Life went on and so did we.
Looking back, I realize that having a miscarriage and working as a physician in the middle of a global pandemic pushed me to my emotional and physical limits. There is a second-guessing of sorts that occurs. Did the miscarriage happen because I was under so much stress at work? It had happened in the past, was this going to continue to happen?
I can say that I was great at compartmentalizing emotions. I’d try and box them away until I got off of work and then turn them on like a switch once I hit the driver’s seat. It’s easy as a busy physician with so many patients to see, messages to return, notes to write, students and residents to teach, and programs to run to completely tune out the thought of mourning. Temporarily anyway. Work was actually a welcome distraction at times. A purpose. The journey to healing is individualized and can’t be rushed. I like to think that I heal a little bit more every day thinking about the losses and gains that I’ve had. I’m grateful for the experience and growth.
In 2022, I’m looking forward to continuing my healing journey among the twists and turns of the pandemic. I now bring a different level of understanding and empathy to my patients who are undergoing or who have undergone a miscarriage. There will always be a piece of me that viscerally mourns with them. We have a hidden shared experience. I believe I am a better physician because of those lessons learned from my own personal tragedy. Now, I look forward to sharing big belly laughs with my family and friends and savoring the small, quiet moments with my husband and daughter.
A version of this article first appeared on Medscape.com.
Buprenorphine may curb opioid-induced respiratory depression
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
Will I really feel better if I eat fermented foods?
I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.
The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!
If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.
Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.
For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.
We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.
So, what about the health claims?
Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.
Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.
Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.
We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.
I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.
Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.
The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!
If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.
Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.
For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.
We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.
So, what about the health claims?
Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.
Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.
Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.
We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.
I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.
Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.
The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!
If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.
Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.
For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.
We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.
So, what about the health claims?
Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.
Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.
Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.
We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.
I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.
Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ketamine versus ECT for depression: First head-to-head results
Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.
In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.
However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.
The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.
Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
Primary focus on remission
The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.
Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%.
Both ketamine and ECT required a median of six treatment sessions to induce remission.
Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.
But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).
The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.
In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.
During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
Let the patient decide
As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine.
“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.
The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.
“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.
If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.
“ or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.
A good alternative
Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”
“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.
He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”
He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”
The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.
“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.
Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.
“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.
The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.
In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.
However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.
The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.
Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
Primary focus on remission
The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.
Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%.
Both ketamine and ECT required a median of six treatment sessions to induce remission.
Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.
But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).
The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.
In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.
During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
Let the patient decide
As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine.
“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.
The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.
“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.
If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.
“ or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.
A good alternative
Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”
“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.
He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”
He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”
The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.
“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.
Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.
“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.
The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.
In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.
However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.
The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.
Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
Primary focus on remission
The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.
Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%.
Both ketamine and ECT required a median of six treatment sessions to induce remission.
Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.
But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).
The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.
In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.
During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
Let the patient decide
As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine.
“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.
The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.
“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.
If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.
“ or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.
A good alternative
Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”
“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.
He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”
He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”
The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.
“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.
Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.
“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.
The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Long COVID is real, and many real questions remain
Long story short, we still have a lot to learn about long COVID-19.
But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.
Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.
Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?
To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.
“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.
Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.
“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.
Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.
Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.
Not all the symptoms are physical either.
“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”
More research will be needed to distinguish the causes of these conditions.
A difficult diagnosis
the experts said.
“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”
Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”
The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
Predicting long COVID
In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.
The study, published in Cell, followed 309 people 2-3 months after COVID-19.
“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
Unexpected patients getting long COVID care
“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.
Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.
Also, instead of just older patients, people of all ages are seeking long COVID care.
One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.
“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
Is an autoinflammatory process to blame?
It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.
There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”
Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”
Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
Also a research opportunity
“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.
“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.
What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
How long will long COVID last?
The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.
Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.
“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.
A version of this article first appeared on WebMD.com.
Long story short, we still have a lot to learn about long COVID-19.
But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.
Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.
Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?
To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.
“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.
Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.
“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.
Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.
Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.
Not all the symptoms are physical either.
“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”
More research will be needed to distinguish the causes of these conditions.
A difficult diagnosis
the experts said.
“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”
Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”
The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
Predicting long COVID
In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.
The study, published in Cell, followed 309 people 2-3 months after COVID-19.
“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
Unexpected patients getting long COVID care
“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.
Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.
Also, instead of just older patients, people of all ages are seeking long COVID care.
One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.
“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
Is an autoinflammatory process to blame?
It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.
There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”
Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”
Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
Also a research opportunity
“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.
“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.
What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
How long will long COVID last?
The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.
Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.
“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.
A version of this article first appeared on WebMD.com.
Long story short, we still have a lot to learn about long COVID-19.
But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.
Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.
Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?
To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.
“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.
Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.
“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.
Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.
Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.
Not all the symptoms are physical either.
“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”
More research will be needed to distinguish the causes of these conditions.
A difficult diagnosis
the experts said.
“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”
Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”
The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
Predicting long COVID
In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.
The study, published in Cell, followed 309 people 2-3 months after COVID-19.
“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
Unexpected patients getting long COVID care
“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.
Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.
Also, instead of just older patients, people of all ages are seeking long COVID care.
One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.
“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
Is an autoinflammatory process to blame?
It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.
There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”
Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”
Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
Also a research opportunity
“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.
“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.
What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
How long will long COVID last?
The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.
Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.
“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.
A version of this article first appeared on WebMD.com.
Early, subtle, cardiac changes tied to midlife cognitive decline
new research suggests.
Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.
“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.
“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.
The findings were published online Jan. 26, 2022, in Neurology.
Heart/brain connection
The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.
Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m2 in year 5 to 86.0 g/m2 in year 30.
Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m2 in year 5 to 26 mL/m2 in year 30.
Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.
After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).
An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.
“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.
“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.
Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.
They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
First structural biomarker
Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.
“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.
As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.
Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”
The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.
Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.
How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.
“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.
“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.
“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.
The findings were published online Jan. 26, 2022, in Neurology.
Heart/brain connection
The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.
Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m2 in year 5 to 86.0 g/m2 in year 30.
Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m2 in year 5 to 26 mL/m2 in year 30.
Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.
After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).
An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.
“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.
“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.
Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.
They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
First structural biomarker
Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.
“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.
As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.
Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”
The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.
Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.
How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.
“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.
“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.
“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.
The findings were published online Jan. 26, 2022, in Neurology.
Heart/brain connection
The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.
Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m2 in year 5 to 86.0 g/m2 in year 30.
Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m2 in year 5 to 26 mL/m2 in year 30.
Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.
After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).
An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.
“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.
“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.
Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.
They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
First structural biomarker
Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.
“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.
As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.
Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”
The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.
Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.
How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.
“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.
The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Ketamine an ‘intriguing new therapy’ for alcoholism
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.