Federal Practitioner

It is a time of significant change as the Military Health System (MHS) transitions to the purview of the Defense Health Agency (DHA). Additionally, the landscape of combat is ever changing, and military medicine needs to evolve to ensure that the lessons learned are utilized to optimize care of the war fighters. The purpose of this review is to evaluate the available literature on existing operational medicine curriculums and make recommendations to restructure current military medicine training to produce operationally prepared clinicians who are informed in operationally focused research principles.

Operational Medicine

Before diving into the importance of creating a curriculum and investing in training for scholarly activity proficiency, operational medicine needs to be defined. It can be defined as medical care provided in an austere environment with limited resources and possibly under hostile conditions. Another way to look at operational medicine is as the evaluation of normal human physiology and pathology under abnormal conditions. The mission set of each of the services is unique. The Marines and Army may operate forward past the wire vulnerable to the environment, gunfire, and improvised explosive devices, remote from fixed medical facilities. The Navy has divers exposed to the risks of decompression sickness. The Air Force has pilots exposed to altitude changes and strains of G-forces during flight. Locations vary from cold high-altitude mountainous regions to high-temperature desolate deserts. Many times, medical practitioners may be remotely stationed, far from specialty or immediate definitive care. Patient care may consist of low-acuity management of individual patients in sick call to mass casualty events where patient numbers and morbidity may outstrip available resources, making the difficult task of triage necessary.

Despite the challenges of being a uniformed physician, the benefits of being embedded is a better understanding of the roles and capability of the unit. Military physicians need to have the unique knowledge of the type of injuries sustained in that particular theater of war, such as differentiating between the trauma pattern and care required for blast injuries vs high-velocity missiles. There are also chemical, biologic, radiologic, and nuclear threats that military physicians need to recognize. Much of what disables a military fighting force is not a direct relationship to combat-related injuries; however, entire units have been taken down by infectious diarrhea or trench foot. There is also a need for familiarity of the infections and parasitology endemic to the particular theater with the aim of implementation of prevention whenever possible.

Military medicine does not fit in any box. Military physicians need to know the job requirements of various specialties, including elements of occupational medicine, such as aircrew piloting high-performance fighters or ground troops fully loaded with body armor and 80-lb backpacks. There are musculoskeletal injuries from the stressors of various military occupations. Working around weaponry and contact with hostile forces will create scenarios requiring emergent and critical care. In addition to physical injuries, there is the mental strain of combat with the risk of imminent personal injury, the guilt of survivorship, dealing with the scars and permanent physical damage of combat, and prolonged separation from family and other support systems.

The National Defense Authorization Act 2017 mandated the establishment of a standardized process to oversee all military graduate medical education (GME) programs with the goal of ensuring medical operational readiness.¹ This is no small task with > 3000 residents in more than 70 specialties, comprising approximately 12% of US residents.^1,2 Presently, 26 to 32% of the medical corps is enrolled in full-time training compared with 12% of the total force.² With significant time and resources expended during this period, it is vital to maximize the potential of the training.

Literature Review

A literature review was performed, evaluating historical precedence of specialized military medical training and research as well as current operational curriculums. Literature search was conducted in the PubMed and Uniformed Services University (USU) Learning Resource databases using the terms “operational medicine curriculum,” “military medicine curriculum,” “operational medicine training,” “military medicine training,” “operational medicine research,” and “military medicine research,” and included all articles from 1997 to 2020. Inclusion criteria included studies that detailed military medicine training programs and/or outcomes. The source types used in this research project included peer-reviewed journal publications—both review articles and original research—from medical and military journals. The citations of these articles were also reviewed for additional usable publications. Secondary sources included official reports and studies by the RAND Corporation, the US Government Accountability Office, and the Institute for Defense Analysis (IDA). Due to lack of literature on the topic, other sources such as talking papers, letters, and formal presentations from subject matter experts were included to showcase the current state and gaps on this topic. Key findings from peer-reviewed publications are presented in Table 1.

Overall, the literature review showed that longitudinal deliberately mapped out curriculums can be well integrated into the existing medical curriculum.³ The military medicine course topics include environmental medicine, applied field medicine, combat casualty care, medical support planning, mass casualty incident preparation, and military-focused problem solving, decision making, and leadership.⁴

One 1997 study looked at the degree of implementation of military unique curriculum in 18 family medicine residencies. Only 30% of residents stated that their program had a specific operational medicine curriculum.5 Salerno and colleagues surveyed current residents and recently graduated internal medicine physicians at 14 facilities in the Army, Air Force, and Navy to determine confidence level with military medicine. More than half did not feel ready to practice deployment medicine; just 19% felt comfortable treating nuclear, biologic, and chemical warfare injuries; and 32% felt unfamiliar with the command and administrative duties. A subgroup analysis showed that USU graduates felt more prepared in these areas compared with civilian program graduates.6 Additional studies showed perceived smoother transition in the first active-duty tour after participation in an operational curriculum.⁷

In addition to in-program training, other options include operational rotations offsite and military courses conducted outside the GME program.¹² Some of these courses may include just-in-time training such as expeditionary medical support system training prior to scheduled deployments. Examples of experiential training are listed in Table 3.

Critical Analysis 

Current gaps were identified in the military medicine training pipeline’s operational medicine curriculum and research programs. The analysis looked at specific components that make the operational medicine curriculum and research unique as well as current readiness goals, to determine how to best align both to meet the mission requirements. Some factors considered included efficiency, cost, program portability, duplication minimization, retention, and sustainability.

Efficiency

A well-created curriculum that meets objectives will require more than an assigned rotation and a few lectures. The most successful ones in the literature review were the ones that were deliberately planned and longitudinal, such as the ones at USU that combined a mixture of classroom and field exercises over the course of 4 years.^4,8 In that way, the curriculum may not be considered time efficient, but if integrated well into the already existing medical training, the production of military physicians who are mission ready upon graduation—ready to serve as military medical leaders and deploy—will be invaluable.

Cost Comparison

Due to the associated overhead of running a training platform and the additional hours of operational training, military GME is more expensive initially compared with civilian outsourcing. In USU, for example, there is an additional 700 hours of operational curriculum alone. This cost difference more than doubles the cost of a USU education vs a Health Professional Scholarship Program (HPSP) scholarship at a civilian medical school. However, a causal analysis performed by the IDA to determine value basis noted that USU graduates deploy almost 3 times as much and serve 6 years longer on active duty.³

After graduating medical school through either accession source, physicians complete specialization training in a GME program. The IDA study noted an average $12,000 increased cost of military GME compared with civilian programs. The analysis included resident compensation and overhead costs of running the program as well as the net cost, which also accounted for resident productivity and workload by training in a military facility.³ Calculations due to mandated budget cuts estimated cost savings of closing the military medical school at < $100 million while significantly impacting the military physician pipeline and operational research output.³

Duplication of Effort

There are already established training programs such as Tactical Combat Casualty Care (TCCC) that could be incorporated into the curriculum to avoid expending additional resources to recreate the wheel. USU has a validated operational training curriculum and may be able to make opportunities available for outside trainees to participate in some of its military-unique training and leadership exercises. Other ways to decrease duplication of effort and improve cost efficiency include focusing on the creation of an academic health system (AHS) and consolidating similar programs to conserve resources. Increasing existing military program sizes will not only ensure the continuation of the military medicine pipeline, but will spread overhead costs over a larger cohort, decrease costs of civilian outsourcing, and ensure the less tangible benefits of military cultural exposure early in trainees’ careers. For example, increasing the class size of USU by 30 students actually reduces the cost per student to $239,000 per year from $253,000, while decreasing the need for HPSP accessions training in civilian programs, making the endeavor overall cost neutral.³

Program Portability

The operational medicine residency has proved that an operational curriculum can be remotely managed and reproduced at a variety of residency specialties.¹² Remote education could be developed and distributed throughout the MHS, such as the proposed USU course Military Medicine and Leadership course.3 Centralized training programs like Global Medicine and C-STARS could be scheduled TDYs during the medical training calendar.

Retention

The military medical school, USU, is the largest military medicine accession source. An IDA report notes that retention of USU graduates is 15.2 years compared with 9.2 years served by civilian trainees. Due to the longevity in service, USU graduates also make up more than 25% of military medical leadership.4 The long-term outcome study that looked at the past 40 years of USU graduates observed that over 70% of graduates served until retirement eligibility and are overrepresented in special operations units.3,13 While some of this longevity may be attributed to the longer USU service contracts, military GME graduates were still noted to be 4 times more likely to commit to a multiyear service contract.¹⁴ A RAND study on the retention of military physicians in the Army, Air Force, and Navy noted that overall retention increased throughout all the services for physicians who went through the military GME pipeline.¹⁵ Conversely, civilian GME training was associated with a 45% chance in leaving active duty.¹⁶

It is theorized that early military acculturation during training increases the likelihood of instilling a sense of mission. Being involved in military GME on the teaching side also showed increased retention rates for 63% of survey respondents.¹⁷ Reduced burnout and increased work satisfaction for those involved in military GME was noted on another faculty satisfaction survey.¹⁷

Sustainability

Programs like USU, which have been around for decades, and the newer operational residency program evolving since 2013 have shown sustainability.^4,11 Dissemination of proven curriculums as well as centralization of already validated training programs can help standardize operational medical training throughout the MHS. In order to flourish at individual programs, the faculty need to be well versed in a train the trainer model and have institutional support. The ability to engage with the line at individual locations may be a factor as well.¹⁸ In regard to research, once residents are taught the principles of scholarly activity, they will have the tools to continue operational medicine research advancements and mentoring students.

Discussion

The 2020 NDAA recommends the establishment of an AHS.3 This step will create a culture of military medical readiness from the top down as congressional mandates push reorganization of the MHS, including military GME programs. An overall restructuring of military medicine will require prioritization of resources toward operational requirements vs the historic significant division of attention to beneficiary care that has caused a lack of unity of effort and additional strain on an already heavily tasked medical force. The changes in military GME are just one aspect of that. It is vital to look at the restructuring with a comprehension of the unique challenges of combat health rather than only from an in-garrison, hospital-based aspect.¹⁹ Benefits of having a military medicine AHS include opportunities to share resources and successful business models as well as foster interdisciplinary teamwork and partnerships with civilian health care facilities and research institutions as a force multiplier.¹⁹

There has been recent discussion about budget cuts, including shutting down USU and military GME and transitioning all training to civilian programs to be cost-effective.⁴ If this were to happen, it would be a step backward from the goal of operational readiness. Maintaining US Department of Defense (DoD) control of the military medicine pipeline has innumerable benefits, including built-in mentorship from operationally-seasoned faculty, military leadership development, proficiency in MHS systems, open communication between GME programs and DoD, and curriculum control to ensure focus on readiness.²⁰ Military GME programs are also a significant production source of military-related scholarly activity. Over fiscal year 2017/2018, 63% of the publications out of the San Antonio Uniformed Services Health Education Consortium—the largest Air Force GME platform and second largest multiservice GME platform—involved military relevant medical topics.¹⁷ Much of the volume of operational research as well as the relevant skills learned and future innovations secondary to conducting this research would be lost if military GME did not exist.^17,21

Practically speaking, military GME provides the majority of the military medicine accessions. For example, a presentation by the Air Force Chief of Physician Education noted that the total military GME pipeline included 2875 students, but direct physician access averaged only 20 physicians a year.²² Even if the decision was made to defer to civilian education, capacity does not exist in civilian GME programs. This is worsened by the increased competitiveness of the GME match with the proliferation of medical schools without concurrent increase in residency spots. The 2018 National Resident Matching Program noted that there were more than 37,103 US and foreign applicants for only 33,000 residency positions, leaving many US applicants unmatched.¹⁷ It is doubtful that the civilian GME programs would be able to absorb the influx of military residents, affecting both the military and civilian medicine pipelines. As a secondary effect, the military treatment centers that house the military GME programs would have to close, with surrounding civilian medical facilities also likely unable to absorb the sudden influx of patients and residents losing the intangible benefits of caring for a military population.¹⁵ This was even recognized by the civilian president of the Accreditation Council for Graduate Medical Education:

Military physicians must be trained in the systems of care that are operative in military medicine, which is significantly unlike civilian medicine in many ways. It is often practiced in circumstances that are not seen in civilian medicine, within care structures that are not encountered in American medical practice… Military medicine has advanced research into the care of individuals suffering traumatic injury, critical care, rehabilitation medicine, prosthetics, psychiatric care of those traumatized, and closed head injury, to name a just a few. The sacrifices of our active military demand these advances, and the American Public benefit from these advances.²¹

Where deficiencies exist in military GME, it is possible to use the growing military-civilian training institution partnerships. Two prime examples are the just-in-time deployment training done with civilian trauma facilities by the Air Force Center for the Sustainment of Trauma Readiness Skills and the Air Force Special Operations Surgical Team-Special Operations Critical Care Evacuation Team being embedded in civilian facilities to maintain trauma, surgical, and emergency care skills. While military physicians can maintain competencies, at the same time, the civilian sector can benefit from the lessons learned in the military in regard to mass casualty and disaster responses. Fostering military and civilian training agreements can also enhance research opportunities.¹

Just as the realities of operational medicine frequently require the military physician to think outside the box, the most successful methods of instruction of military medicine tend to be nontraditional. Classroom education should be involved beyond lectures and can include other methods, such as case-based, role-playing, small group discussion, and computer-based teaching. Maintaining flexibility in live vs distance learning as well as synchronous vs asynchronous learning can expand the capacity of available instructors and standardize material over several sites.²³ Asking learners to consider operational concerns, such as whether certain medical conditions would be compatible with military duty in addition to the routine investigation is an easy way to incorporate military training in preexisting medical training.¹² The advancement of technology has made simulation one of the best ways to engage in hands-on learning, whether through computer simulations, animal models, standardized or moulaged patients, or mannequins that can realistically mimic medical or trauma-related conditions.²⁴ Many times, simulation can be combined with exercises in the field to create a realistic operational environment.²³

There are 3 pillars of an operational curriculum that should be integrated into the existing residency curriculum—operational medicine, leadership, and research principles (Appendix).

Conclusions

Judging by the continuing operational tempo and evolution of warfare, maintaining enhanced military medical readiness will remain a priority. Operational medicine is a unique field that requires specialized preparation. Studies have shown that longitudinal deliberately mapped out curriculums are able to be integrated well into the existing medical curriculum. The recommendation moving forward is increasing the access of existing operational training structures that have well established programs and modeling individual GME program curriculums after those that have shown proven success with a focus on the 3 pillars of operational training, leadership, and research.

Acknowledgments

Previously submitted in April 2020 in expanded form as part of graduation requirements for the Masters of Military Arts and Science degree program at Air University, Maxwell Air Force Base in Alabama.

It is a time of significant change as the Military Health System (MHS) transitions to the purview of the Defense Health Agency (DHA). Additionally, the landscape of combat is ever changing, and military medicine needs to evolve to ensure that the lessons learned are utilized to optimize care of the war fighters. The purpose of this review is to evaluate the available literature on existing operational medicine curriculums and make recommendations to restructure current military medicine training to produce operationally prepared clinicians who are informed in operationally focused research principles.

Operational Medicine

Before diving into the importance of creating a curriculum and investing in training for scholarly activity proficiency, operational medicine needs to be defined. It can be defined as medical care provided in an austere environment with limited resources and possibly under hostile conditions. Another way to look at operational medicine is as the evaluation of normal human physiology and pathology under abnormal conditions. The mission set of each of the services is unique. The Marines and Army may operate forward past the wire vulnerable to the environment, gunfire, and improvised explosive devices, remote from fixed medical facilities. The Navy has divers exposed to the risks of decompression sickness. The Air Force has pilots exposed to altitude changes and strains of G-forces during flight. Locations vary from cold high-altitude mountainous regions to high-temperature desolate deserts. Many times, medical practitioners may be remotely stationed, far from specialty or immediate definitive care. Patient care may consist of low-acuity management of individual patients in sick call to mass casualty events where patient numbers and morbidity may outstrip available resources, making the difficult task of triage necessary.

Despite the challenges of being a uniformed physician, the benefits of being embedded is a better understanding of the roles and capability of the unit. Military physicians need to have the unique knowledge of the type of injuries sustained in that particular theater of war, such as differentiating between the trauma pattern and care required for blast injuries vs high-velocity missiles. There are also chemical, biologic, radiologic, and nuclear threats that military physicians need to recognize. Much of what disables a military fighting force is not a direct relationship to combat-related injuries; however, entire units have been taken down by infectious diarrhea or trench foot. There is also a need for familiarity of the infections and parasitology endemic to the particular theater with the aim of implementation of prevention whenever possible.

Military medicine does not fit in any box. Military physicians need to know the job requirements of various specialties, including elements of occupational medicine, such as aircrew piloting high-performance fighters or ground troops fully loaded with body armor and 80-lb backpacks. There are musculoskeletal injuries from the stressors of various military occupations. Working around weaponry and contact with hostile forces will create scenarios requiring emergent and critical care. In addition to physical injuries, there is the mental strain of combat with the risk of imminent personal injury, the guilt of survivorship, dealing with the scars and permanent physical damage of combat, and prolonged separation from family and other support systems.

The National Defense Authorization Act 2017 mandated the establishment of a standardized process to oversee all military graduate medical education (GME) programs with the goal of ensuring medical operational readiness.¹ This is no small task with > 3000 residents in more than 70 specialties, comprising approximately 12% of US residents.^1,2 Presently, 26 to 32% of the medical corps is enrolled in full-time training compared with 12% of the total force.² With significant time and resources expended during this period, it is vital to maximize the potential of the training.

Literature Review

A literature review was performed, evaluating historical precedence of specialized military medical training and research as well as current operational curriculums. Literature search was conducted in the PubMed and Uniformed Services University (USU) Learning Resource databases using the terms “operational medicine curriculum,” “military medicine curriculum,” “operational medicine training,” “military medicine training,” “operational medicine research,” and “military medicine research,” and included all articles from 1997 to 2020. Inclusion criteria included studies that detailed military medicine training programs and/or outcomes. The source types used in this research project included peer-reviewed journal publications—both review articles and original research—from medical and military journals. The citations of these articles were also reviewed for additional usable publications. Secondary sources included official reports and studies by the RAND Corporation, the US Government Accountability Office, and the Institute for Defense Analysis (IDA). Due to lack of literature on the topic, other sources such as talking papers, letters, and formal presentations from subject matter experts were included to showcase the current state and gaps on this topic. Key findings from peer-reviewed publications are presented in Table 1.

Overall, the literature review showed that longitudinal deliberately mapped out curriculums can be well integrated into the existing medical curriculum.³ The military medicine course topics include environmental medicine, applied field medicine, combat casualty care, medical support planning, mass casualty incident preparation, and military-focused problem solving, decision making, and leadership.⁴

One 1997 study looked at the degree of implementation of military unique curriculum in 18 family medicine residencies. Only 30% of residents stated that their program had a specific operational medicine curriculum.5 Salerno and colleagues surveyed current residents and recently graduated internal medicine physicians at 14 facilities in the Army, Air Force, and Navy to determine confidence level with military medicine. More than half did not feel ready to practice deployment medicine; just 19% felt comfortable treating nuclear, biologic, and chemical warfare injuries; and 32% felt unfamiliar with the command and administrative duties. A subgroup analysis showed that USU graduates felt more prepared in these areas compared with civilian program graduates.6 Additional studies showed perceived smoother transition in the first active-duty tour after participation in an operational curriculum.⁷

In addition to in-program training, other options include operational rotations offsite and military courses conducted outside the GME program.¹² Some of these courses may include just-in-time training such as expeditionary medical support system training prior to scheduled deployments. Examples of experiential training are listed in Table 3.

Critical Analysis 

Current gaps were identified in the military medicine training pipeline’s operational medicine curriculum and research programs. The analysis looked at specific components that make the operational medicine curriculum and research unique as well as current readiness goals, to determine how to best align both to meet the mission requirements. Some factors considered included efficiency, cost, program portability, duplication minimization, retention, and sustainability.

Efficiency

A well-created curriculum that meets objectives will require more than an assigned rotation and a few lectures. The most successful ones in the literature review were the ones that were deliberately planned and longitudinal, such as the ones at USU that combined a mixture of classroom and field exercises over the course of 4 years.^4,8 In that way, the curriculum may not be considered time efficient, but if integrated well into the already existing medical training, the production of military physicians who are mission ready upon graduation—ready to serve as military medical leaders and deploy—will be invaluable.

Cost Comparison

Due to the associated overhead of running a training platform and the additional hours of operational training, military GME is more expensive initially compared with civilian outsourcing. In USU, for example, there is an additional 700 hours of operational curriculum alone. This cost difference more than doubles the cost of a USU education vs a Health Professional Scholarship Program (HPSP) scholarship at a civilian medical school. However, a causal analysis performed by the IDA to determine value basis noted that USU graduates deploy almost 3 times as much and serve 6 years longer on active duty.³

After graduating medical school through either accession source, physicians complete specialization training in a GME program. The IDA study noted an average $12,000 increased cost of military GME compared with civilian programs. The analysis included resident compensation and overhead costs of running the program as well as the net cost, which also accounted for resident productivity and workload by training in a military facility.³ Calculations due to mandated budget cuts estimated cost savings of closing the military medical school at < $100 million while significantly impacting the military physician pipeline and operational research output.³

Duplication of Effort

There are already established training programs such as Tactical Combat Casualty Care (TCCC) that could be incorporated into the curriculum to avoid expending additional resources to recreate the wheel. USU has a validated operational training curriculum and may be able to make opportunities available for outside trainees to participate in some of its military-unique training and leadership exercises. Other ways to decrease duplication of effort and improve cost efficiency include focusing on the creation of an academic health system (AHS) and consolidating similar programs to conserve resources. Increasing existing military program sizes will not only ensure the continuation of the military medicine pipeline, but will spread overhead costs over a larger cohort, decrease costs of civilian outsourcing, and ensure the less tangible benefits of military cultural exposure early in trainees’ careers. For example, increasing the class size of USU by 30 students actually reduces the cost per student to $239,000 per year from $253,000, while decreasing the need for HPSP accessions training in civilian programs, making the endeavor overall cost neutral.³

Program Portability

The operational medicine residency has proved that an operational curriculum can be remotely managed and reproduced at a variety of residency specialties.¹² Remote education could be developed and distributed throughout the MHS, such as the proposed USU course Military Medicine and Leadership course.3 Centralized training programs like Global Medicine and C-STARS could be scheduled TDYs during the medical training calendar.

Retention

The military medical school, USU, is the largest military medicine accession source. An IDA report notes that retention of USU graduates is 15.2 years compared with 9.2 years served by civilian trainees. Due to the longevity in service, USU graduates also make up more than 25% of military medical leadership.4 The long-term outcome study that looked at the past 40 years of USU graduates observed that over 70% of graduates served until retirement eligibility and are overrepresented in special operations units.3,13 While some of this longevity may be attributed to the longer USU service contracts, military GME graduates were still noted to be 4 times more likely to commit to a multiyear service contract.¹⁴ A RAND study on the retention of military physicians in the Army, Air Force, and Navy noted that overall retention increased throughout all the services for physicians who went through the military GME pipeline.¹⁵ Conversely, civilian GME training was associated with a 45% chance in leaving active duty.¹⁶

It is theorized that early military acculturation during training increases the likelihood of instilling a sense of mission. Being involved in military GME on the teaching side also showed increased retention rates for 63% of survey respondents.¹⁷ Reduced burnout and increased work satisfaction for those involved in military GME was noted on another faculty satisfaction survey.¹⁷

Sustainability

Programs like USU, which have been around for decades, and the newer operational residency program evolving since 2013 have shown sustainability.^4,11 Dissemination of proven curriculums as well as centralization of already validated training programs can help standardize operational medical training throughout the MHS. In order to flourish at individual programs, the faculty need to be well versed in a train the trainer model and have institutional support. The ability to engage with the line at individual locations may be a factor as well.¹⁸ In regard to research, once residents are taught the principles of scholarly activity, they will have the tools to continue operational medicine research advancements and mentoring students.

Discussion

The 2020 NDAA recommends the establishment of an AHS.3 This step will create a culture of military medical readiness from the top down as congressional mandates push reorganization of the MHS, including military GME programs. An overall restructuring of military medicine will require prioritization of resources toward operational requirements vs the historic significant division of attention to beneficiary care that has caused a lack of unity of effort and additional strain on an already heavily tasked medical force. The changes in military GME are just one aspect of that. It is vital to look at the restructuring with a comprehension of the unique challenges of combat health rather than only from an in-garrison, hospital-based aspect.¹⁹ Benefits of having a military medicine AHS include opportunities to share resources and successful business models as well as foster interdisciplinary teamwork and partnerships with civilian health care facilities and research institutions as a force multiplier.¹⁹

There has been recent discussion about budget cuts, including shutting down USU and military GME and transitioning all training to civilian programs to be cost-effective.⁴ If this were to happen, it would be a step backward from the goal of operational readiness. Maintaining US Department of Defense (DoD) control of the military medicine pipeline has innumerable benefits, including built-in mentorship from operationally-seasoned faculty, military leadership development, proficiency in MHS systems, open communication between GME programs and DoD, and curriculum control to ensure focus on readiness.²⁰ Military GME programs are also a significant production source of military-related scholarly activity. Over fiscal year 2017/2018, 63% of the publications out of the San Antonio Uniformed Services Health Education Consortium—the largest Air Force GME platform and second largest multiservice GME platform—involved military relevant medical topics.¹⁷ Much of the volume of operational research as well as the relevant skills learned and future innovations secondary to conducting this research would be lost if military GME did not exist.^17,21

Practically speaking, military GME provides the majority of the military medicine accessions. For example, a presentation by the Air Force Chief of Physician Education noted that the total military GME pipeline included 2875 students, but direct physician access averaged only 20 physicians a year.²² Even if the decision was made to defer to civilian education, capacity does not exist in civilian GME programs. This is worsened by the increased competitiveness of the GME match with the proliferation of medical schools without concurrent increase in residency spots. The 2018 National Resident Matching Program noted that there were more than 37,103 US and foreign applicants for only 33,000 residency positions, leaving many US applicants unmatched.¹⁷ It is doubtful that the civilian GME programs would be able to absorb the influx of military residents, affecting both the military and civilian medicine pipelines. As a secondary effect, the military treatment centers that house the military GME programs would have to close, with surrounding civilian medical facilities also likely unable to absorb the sudden influx of patients and residents losing the intangible benefits of caring for a military population.¹⁵ This was even recognized by the civilian president of the Accreditation Council for Graduate Medical Education:

Military physicians must be trained in the systems of care that are operative in military medicine, which is significantly unlike civilian medicine in many ways. It is often practiced in circumstances that are not seen in civilian medicine, within care structures that are not encountered in American medical practice… Military medicine has advanced research into the care of individuals suffering traumatic injury, critical care, rehabilitation medicine, prosthetics, psychiatric care of those traumatized, and closed head injury, to name a just a few. The sacrifices of our active military demand these advances, and the American Public benefit from these advances.²¹

Where deficiencies exist in military GME, it is possible to use the growing military-civilian training institution partnerships. Two prime examples are the just-in-time deployment training done with civilian trauma facilities by the Air Force Center for the Sustainment of Trauma Readiness Skills and the Air Force Special Operations Surgical Team-Special Operations Critical Care Evacuation Team being embedded in civilian facilities to maintain trauma, surgical, and emergency care skills. While military physicians can maintain competencies, at the same time, the civilian sector can benefit from the lessons learned in the military in regard to mass casualty and disaster responses. Fostering military and civilian training agreements can also enhance research opportunities.¹

Just as the realities of operational medicine frequently require the military physician to think outside the box, the most successful methods of instruction of military medicine tend to be nontraditional. Classroom education should be involved beyond lectures and can include other methods, such as case-based, role-playing, small group discussion, and computer-based teaching. Maintaining flexibility in live vs distance learning as well as synchronous vs asynchronous learning can expand the capacity of available instructors and standardize material over several sites.²³ Asking learners to consider operational concerns, such as whether certain medical conditions would be compatible with military duty in addition to the routine investigation is an easy way to incorporate military training in preexisting medical training.¹² The advancement of technology has made simulation one of the best ways to engage in hands-on learning, whether through computer simulations, animal models, standardized or moulaged patients, or mannequins that can realistically mimic medical or trauma-related conditions.²⁴ Many times, simulation can be combined with exercises in the field to create a realistic operational environment.²³

There are 3 pillars of an operational curriculum that should be integrated into the existing residency curriculum—operational medicine, leadership, and research principles (Appendix).

Conclusions

Judging by the continuing operational tempo and evolution of warfare, maintaining enhanced military medical readiness will remain a priority. Operational medicine is a unique field that requires specialized preparation. Studies have shown that longitudinal deliberately mapped out curriculums are able to be integrated well into the existing medical curriculum. The recommendation moving forward is increasing the access of existing operational training structures that have well established programs and modeling individual GME program curriculums after those that have shown proven success with a focus on the 3 pillars of operational training, leadership, and research.

Acknowledgments

Previously submitted in April 2020 in expanded form as part of graduation requirements for the Masters of Military Arts and Science degree program at Air University, Maxwell Air Force Base in Alabama.

It is a time of significant change as the Military Health System (MHS) transitions to the purview of the Defense Health Agency (DHA). Additionally, the landscape of combat is ever changing, and military medicine needs to evolve to ensure that the lessons learned are utilized to optimize care of the war fighters. The purpose of this review is to evaluate the available literature on existing operational medicine curriculums and make recommendations to restructure current military medicine training to produce operationally prepared clinicians who are informed in operationally focused research principles.

Operational Medicine

Before diving into the importance of creating a curriculum and investing in training for scholarly activity proficiency, operational medicine needs to be defined. It can be defined as medical care provided in an austere environment with limited resources and possibly under hostile conditions. Another way to look at operational medicine is as the evaluation of normal human physiology and pathology under abnormal conditions. The mission set of each of the services is unique. The Marines and Army may operate forward past the wire vulnerable to the environment, gunfire, and improvised explosive devices, remote from fixed medical facilities. The Navy has divers exposed to the risks of decompression sickness. The Air Force has pilots exposed to altitude changes and strains of G-forces during flight. Locations vary from cold high-altitude mountainous regions to high-temperature desolate deserts. Many times, medical practitioners may be remotely stationed, far from specialty or immediate definitive care. Patient care may consist of low-acuity management of individual patients in sick call to mass casualty events where patient numbers and morbidity may outstrip available resources, making the difficult task of triage necessary.

Despite the challenges of being a uniformed physician, the benefits of being embedded is a better understanding of the roles and capability of the unit. Military physicians need to have the unique knowledge of the type of injuries sustained in that particular theater of war, such as differentiating between the trauma pattern and care required for blast injuries vs high-velocity missiles. There are also chemical, biologic, radiologic, and nuclear threats that military physicians need to recognize. Much of what disables a military fighting force is not a direct relationship to combat-related injuries; however, entire units have been taken down by infectious diarrhea or trench foot. There is also a need for familiarity of the infections and parasitology endemic to the particular theater with the aim of implementation of prevention whenever possible.

Military medicine does not fit in any box. Military physicians need to know the job requirements of various specialties, including elements of occupational medicine, such as aircrew piloting high-performance fighters or ground troops fully loaded with body armor and 80-lb backpacks. There are musculoskeletal injuries from the stressors of various military occupations. Working around weaponry and contact with hostile forces will create scenarios requiring emergent and critical care. In addition to physical injuries, there is the mental strain of combat with the risk of imminent personal injury, the guilt of survivorship, dealing with the scars and permanent physical damage of combat, and prolonged separation from family and other support systems.

The National Defense Authorization Act 2017 mandated the establishment of a standardized process to oversee all military graduate medical education (GME) programs with the goal of ensuring medical operational readiness.¹ This is no small task with > 3000 residents in more than 70 specialties, comprising approximately 12% of US residents.^1,2 Presently, 26 to 32% of the medical corps is enrolled in full-time training compared with 12% of the total force.² With significant time and resources expended during this period, it is vital to maximize the potential of the training.

Literature Review

A literature review was performed, evaluating historical precedence of specialized military medical training and research as well as current operational curriculums. Literature search was conducted in the PubMed and Uniformed Services University (USU) Learning Resource databases using the terms “operational medicine curriculum,” “military medicine curriculum,” “operational medicine training,” “military medicine training,” “operational medicine research,” and “military medicine research,” and included all articles from 1997 to 2020. Inclusion criteria included studies that detailed military medicine training programs and/or outcomes. The source types used in this research project included peer-reviewed journal publications—both review articles and original research—from medical and military journals. The citations of these articles were also reviewed for additional usable publications. Secondary sources included official reports and studies by the RAND Corporation, the US Government Accountability Office, and the Institute for Defense Analysis (IDA). Due to lack of literature on the topic, other sources such as talking papers, letters, and formal presentations from subject matter experts were included to showcase the current state and gaps on this topic. Key findings from peer-reviewed publications are presented in Table 1.

Overall, the literature review showed that longitudinal deliberately mapped out curriculums can be well integrated into the existing medical curriculum.³ The military medicine course topics include environmental medicine, applied field medicine, combat casualty care, medical support planning, mass casualty incident preparation, and military-focused problem solving, decision making, and leadership.⁴

One 1997 study looked at the degree of implementation of military unique curriculum in 18 family medicine residencies. Only 30% of residents stated that their program had a specific operational medicine curriculum.5 Salerno and colleagues surveyed current residents and recently graduated internal medicine physicians at 14 facilities in the Army, Air Force, and Navy to determine confidence level with military medicine. More than half did not feel ready to practice deployment medicine; just 19% felt comfortable treating nuclear, biologic, and chemical warfare injuries; and 32% felt unfamiliar with the command and administrative duties. A subgroup analysis showed that USU graduates felt more prepared in these areas compared with civilian program graduates.6 Additional studies showed perceived smoother transition in the first active-duty tour after participation in an operational curriculum.⁷

In addition to in-program training, other options include operational rotations offsite and military courses conducted outside the GME program.¹² Some of these courses may include just-in-time training such as expeditionary medical support system training prior to scheduled deployments. Examples of experiential training are listed in Table 3.

Critical Analysis 

Current gaps were identified in the military medicine training pipeline’s operational medicine curriculum and research programs. The analysis looked at specific components that make the operational medicine curriculum and research unique as well as current readiness goals, to determine how to best align both to meet the mission requirements. Some factors considered included efficiency, cost, program portability, duplication minimization, retention, and sustainability.

Efficiency

A well-created curriculum that meets objectives will require more than an assigned rotation and a few lectures. The most successful ones in the literature review were the ones that were deliberately planned and longitudinal, such as the ones at USU that combined a mixture of classroom and field exercises over the course of 4 years.^4,8 In that way, the curriculum may not be considered time efficient, but if integrated well into the already existing medical training, the production of military physicians who are mission ready upon graduation—ready to serve as military medical leaders and deploy—will be invaluable.

Cost Comparison

Due to the associated overhead of running a training platform and the additional hours of operational training, military GME is more expensive initially compared with civilian outsourcing. In USU, for example, there is an additional 700 hours of operational curriculum alone. This cost difference more than doubles the cost of a USU education vs a Health Professional Scholarship Program (HPSP) scholarship at a civilian medical school. However, a causal analysis performed by the IDA to determine value basis noted that USU graduates deploy almost 3 times as much and serve 6 years longer on active duty.³

After graduating medical school through either accession source, physicians complete specialization training in a GME program. The IDA study noted an average $12,000 increased cost of military GME compared with civilian programs. The analysis included resident compensation and overhead costs of running the program as well as the net cost, which also accounted for resident productivity and workload by training in a military facility.³ Calculations due to mandated budget cuts estimated cost savings of closing the military medical school at < $100 million while significantly impacting the military physician pipeline and operational research output.³

Duplication of Effort

There are already established training programs such as Tactical Combat Casualty Care (TCCC) that could be incorporated into the curriculum to avoid expending additional resources to recreate the wheel. USU has a validated operational training curriculum and may be able to make opportunities available for outside trainees to participate in some of its military-unique training and leadership exercises. Other ways to decrease duplication of effort and improve cost efficiency include focusing on the creation of an academic health system (AHS) and consolidating similar programs to conserve resources. Increasing existing military program sizes will not only ensure the continuation of the military medicine pipeline, but will spread overhead costs over a larger cohort, decrease costs of civilian outsourcing, and ensure the less tangible benefits of military cultural exposure early in trainees’ careers. For example, increasing the class size of USU by 30 students actually reduces the cost per student to $239,000 per year from $253,000, while decreasing the need for HPSP accessions training in civilian programs, making the endeavor overall cost neutral.³

Program Portability

The operational medicine residency has proved that an operational curriculum can be remotely managed and reproduced at a variety of residency specialties.¹² Remote education could be developed and distributed throughout the MHS, such as the proposed USU course Military Medicine and Leadership course.3 Centralized training programs like Global Medicine and C-STARS could be scheduled TDYs during the medical training calendar.

Retention

The military medical school, USU, is the largest military medicine accession source. An IDA report notes that retention of USU graduates is 15.2 years compared with 9.2 years served by civilian trainees. Due to the longevity in service, USU graduates also make up more than 25% of military medical leadership.4 The long-term outcome study that looked at the past 40 years of USU graduates observed that over 70% of graduates served until retirement eligibility and are overrepresented in special operations units.3,13 While some of this longevity may be attributed to the longer USU service contracts, military GME graduates were still noted to be 4 times more likely to commit to a multiyear service contract.¹⁴ A RAND study on the retention of military physicians in the Army, Air Force, and Navy noted that overall retention increased throughout all the services for physicians who went through the military GME pipeline.¹⁵ Conversely, civilian GME training was associated with a 45% chance in leaving active duty.¹⁶

It is theorized that early military acculturation during training increases the likelihood of instilling a sense of mission. Being involved in military GME on the teaching side also showed increased retention rates for 63% of survey respondents.¹⁷ Reduced burnout and increased work satisfaction for those involved in military GME was noted on another faculty satisfaction survey.¹⁷

Sustainability

Programs like USU, which have been around for decades, and the newer operational residency program evolving since 2013 have shown sustainability.^4,11 Dissemination of proven curriculums as well as centralization of already validated training programs can help standardize operational medical training throughout the MHS. In order to flourish at individual programs, the faculty need to be well versed in a train the trainer model and have institutional support. The ability to engage with the line at individual locations may be a factor as well.¹⁸ In regard to research, once residents are taught the principles of scholarly activity, they will have the tools to continue operational medicine research advancements and mentoring students.

Discussion

The 2020 NDAA recommends the establishment of an AHS.3 This step will create a culture of military medical readiness from the top down as congressional mandates push reorganization of the MHS, including military GME programs. An overall restructuring of military medicine will require prioritization of resources toward operational requirements vs the historic significant division of attention to beneficiary care that has caused a lack of unity of effort and additional strain on an already heavily tasked medical force. The changes in military GME are just one aspect of that. It is vital to look at the restructuring with a comprehension of the unique challenges of combat health rather than only from an in-garrison, hospital-based aspect.¹⁹ Benefits of having a military medicine AHS include opportunities to share resources and successful business models as well as foster interdisciplinary teamwork and partnerships with civilian health care facilities and research institutions as a force multiplier.¹⁹

There has been recent discussion about budget cuts, including shutting down USU and military GME and transitioning all training to civilian programs to be cost-effective.⁴ If this were to happen, it would be a step backward from the goal of operational readiness. Maintaining US Department of Defense (DoD) control of the military medicine pipeline has innumerable benefits, including built-in mentorship from operationally-seasoned faculty, military leadership development, proficiency in MHS systems, open communication between GME programs and DoD, and curriculum control to ensure focus on readiness.²⁰ Military GME programs are also a significant production source of military-related scholarly activity. Over fiscal year 2017/2018, 63% of the publications out of the San Antonio Uniformed Services Health Education Consortium—the largest Air Force GME platform and second largest multiservice GME platform—involved military relevant medical topics.¹⁷ Much of the volume of operational research as well as the relevant skills learned and future innovations secondary to conducting this research would be lost if military GME did not exist.^17,21

Practically speaking, military GME provides the majority of the military medicine accessions. For example, a presentation by the Air Force Chief of Physician Education noted that the total military GME pipeline included 2875 students, but direct physician access averaged only 20 physicians a year.²² Even if the decision was made to defer to civilian education, capacity does not exist in civilian GME programs. This is worsened by the increased competitiveness of the GME match with the proliferation of medical schools without concurrent increase in residency spots. The 2018 National Resident Matching Program noted that there were more than 37,103 US and foreign applicants for only 33,000 residency positions, leaving many US applicants unmatched.¹⁷ It is doubtful that the civilian GME programs would be able to absorb the influx of military residents, affecting both the military and civilian medicine pipelines. As a secondary effect, the military treatment centers that house the military GME programs would have to close, with surrounding civilian medical facilities also likely unable to absorb the sudden influx of patients and residents losing the intangible benefits of caring for a military population.¹⁵ This was even recognized by the civilian president of the Accreditation Council for Graduate Medical Education:

Military physicians must be trained in the systems of care that are operative in military medicine, which is significantly unlike civilian medicine in many ways. It is often practiced in circumstances that are not seen in civilian medicine, within care structures that are not encountered in American medical practice… Military medicine has advanced research into the care of individuals suffering traumatic injury, critical care, rehabilitation medicine, prosthetics, psychiatric care of those traumatized, and closed head injury, to name a just a few. The sacrifices of our active military demand these advances, and the American Public benefit from these advances.²¹

Where deficiencies exist in military GME, it is possible to use the growing military-civilian training institution partnerships. Two prime examples are the just-in-time deployment training done with civilian trauma facilities by the Air Force Center for the Sustainment of Trauma Readiness Skills and the Air Force Special Operations Surgical Team-Special Operations Critical Care Evacuation Team being embedded in civilian facilities to maintain trauma, surgical, and emergency care skills. While military physicians can maintain competencies, at the same time, the civilian sector can benefit from the lessons learned in the military in regard to mass casualty and disaster responses. Fostering military and civilian training agreements can also enhance research opportunities.¹

Just as the realities of operational medicine frequently require the military physician to think outside the box, the most successful methods of instruction of military medicine tend to be nontraditional. Classroom education should be involved beyond lectures and can include other methods, such as case-based, role-playing, small group discussion, and computer-based teaching. Maintaining flexibility in live vs distance learning as well as synchronous vs asynchronous learning can expand the capacity of available instructors and standardize material over several sites.²³ Asking learners to consider operational concerns, such as whether certain medical conditions would be compatible with military duty in addition to the routine investigation is an easy way to incorporate military training in preexisting medical training.¹² The advancement of technology has made simulation one of the best ways to engage in hands-on learning, whether through computer simulations, animal models, standardized or moulaged patients, or mannequins that can realistically mimic medical or trauma-related conditions.²⁴ Many times, simulation can be combined with exercises in the field to create a realistic operational environment.²³

There are 3 pillars of an operational curriculum that should be integrated into the existing residency curriculum—operational medicine, leadership, and research principles (Appendix).

Conclusions

Judging by the continuing operational tempo and evolution of warfare, maintaining enhanced military medical readiness will remain a priority. Operational medicine is a unique field that requires specialized preparation. Studies have shown that longitudinal deliberately mapped out curriculums are able to be integrated well into the existing medical curriculum. The recommendation moving forward is increasing the access of existing operational training structures that have well established programs and modeling individual GME program curriculums after those that have shown proven success with a focus on the 3 pillars of operational training, leadership, and research.

Acknowledgments

Previously submitted in April 2020 in expanded form as part of graduation requirements for the Masters of Military Arts and Science degree program at Air University, Maxwell Air Force Base in Alabama.

To the Editor: September is National Suicide Prevention and Awareness month. In 2021, the US Department of Veterans Affairs (VA) Office of Mental Health and Suicide Prevention marked the month by demonstrating why it is the national visionary when it comes to preventing suicide. The office rolled out several public service announcements (PSAs) about creating “space between thought and trigger.”¹ These incredibly sensitive spots, the first of their kind, encourage safer storage and reduced access to firearms at points of heightened crises. The PSAs are timely, especially given the just released annual report showing that 69.2% of veteran suicide deaths are by firearm.² Wide PSA dissemination is vital.

But concerningly, the PSAs completely missed the importance of critical partnerships. As described in Federal Practitioner 2 years ago, VA forged a groundbreaking collaboration with the National Shooting Sports Foundation (NSSF), the firearms industry trade association, and the American Foundation for Suicide Prevention (AFSP).³ Having NSSF as a partner advanced VA’s effort to ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and contains no antifirearm bias. Since then, VA and NSSF cobranded billboards in 8 states, encouraging storing firearms responsibly to prevent suicide. They collectively developed an educational, training, and resource toolkit that guides communities through the process of building coalitions to raise awareness about securely storing firearms when not in use.⁴ VA and NSSF have cross-listed safe storage websites. In May 2020, the VA cosponsored a COVID-19 suicide prevention video with the NSSF, AFSP, and the US Concealed Carry Association, including ways that the firearm industry, gun owners, and their families can help.⁵

Yet when the VA launched its PSA campaign last month, NSSF’s name was conspicuously absent. That must be corrected going forward. Reaching vulnerable veterans who own firearms requires partnerships with individuals and groups who own firearms. Going it alone undercuts the essence of what VA has worked so hard to achieve in the past few years.

Russell B. Lemle, PhD
Veterans Healthcare
Policy Institute

To the Editor: September is National Suicide Prevention and Awareness month. In 2021, the US Department of Veterans Affairs (VA) Office of Mental Health and Suicide Prevention marked the month by demonstrating why it is the national visionary when it comes to preventing suicide. The office rolled out several public service announcements (PSAs) about creating “space between thought and trigger.”¹ These incredibly sensitive spots, the first of their kind, encourage safer storage and reduced access to firearms at points of heightened crises. The PSAs are timely, especially given the just released annual report showing that 69.2% of veteran suicide deaths are by firearm.² Wide PSA dissemination is vital.

But concerningly, the PSAs completely missed the importance of critical partnerships. As described in Federal Practitioner 2 years ago, VA forged a groundbreaking collaboration with the National Shooting Sports Foundation (NSSF), the firearms industry trade association, and the American Foundation for Suicide Prevention (AFSP).³ Having NSSF as a partner advanced VA’s effort to ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and contains no antifirearm bias. Since then, VA and NSSF cobranded billboards in 8 states, encouraging storing firearms responsibly to prevent suicide. They collectively developed an educational, training, and resource toolkit that guides communities through the process of building coalitions to raise awareness about securely storing firearms when not in use.⁴ VA and NSSF have cross-listed safe storage websites. In May 2020, the VA cosponsored a COVID-19 suicide prevention video with the NSSF, AFSP, and the US Concealed Carry Association, including ways that the firearm industry, gun owners, and their families can help.⁵

Yet when the VA launched its PSA campaign last month, NSSF’s name was conspicuously absent. That must be corrected going forward. Reaching vulnerable veterans who own firearms requires partnerships with individuals and groups who own firearms. Going it alone undercuts the essence of what VA has worked so hard to achieve in the past few years.

Russell B. Lemle, PhD
Veterans Healthcare
Policy Institute

To the Editor: September is National Suicide Prevention and Awareness month. In 2021, the US Department of Veterans Affairs (VA) Office of Mental Health and Suicide Prevention marked the month by demonstrating why it is the national visionary when it comes to preventing suicide. The office rolled out several public service announcements (PSAs) about creating “space between thought and trigger.”¹ These incredibly sensitive spots, the first of their kind, encourage safer storage and reduced access to firearms at points of heightened crises. The PSAs are timely, especially given the just released annual report showing that 69.2% of veteran suicide deaths are by firearm.² Wide PSA dissemination is vital.

But concerningly, the PSAs completely missed the importance of critical partnerships. As described in Federal Practitioner 2 years ago, VA forged a groundbreaking collaboration with the National Shooting Sports Foundation (NSSF), the firearms industry trade association, and the American Foundation for Suicide Prevention (AFSP).³ Having NSSF as a partner advanced VA’s effort to ensure that lethal means safety counseling is culturally relevant, comes from a trusted source, and contains no antifirearm bias. Since then, VA and NSSF cobranded billboards in 8 states, encouraging storing firearms responsibly to prevent suicide. They collectively developed an educational, training, and resource toolkit that guides communities through the process of building coalitions to raise awareness about securely storing firearms when not in use.⁴ VA and NSSF have cross-listed safe storage websites. In May 2020, the VA cosponsored a COVID-19 suicide prevention video with the NSSF, AFSP, and the US Concealed Carry Association, including ways that the firearm industry, gun owners, and their families can help.⁵

Yet when the VA launched its PSA campaign last month, NSSF’s name was conspicuously absent. That must be corrected going forward. Reaching vulnerable veterans who own firearms requires partnerships with individuals and groups who own firearms. Going it alone undercuts the essence of what VA has worked so hard to achieve in the past few years.

Russell B. Lemle, PhD
Veterans Healthcare
Policy Institute

Hot flashes affect three out of four women and can last 7-10 years, but the current standard of care treatment isn’t necessarily appropriate for all women who experience vasomotor symptoms, according to Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health Clinic in Jacksonville, Fla.

For the majority of women under age 60 who are within 10 years of menopause, hormone therapy currently remains the most effective management option for hot flashes where the benefits outweigh the risks, Dr. Faubion told attendees Sept. 25 during a plenary at the annual meeting of the North American Menopause Society. “But really, individualizing treatment is the goal, and there are some women who are going to need some other options.”

Contraindications for hormone therapy include having a history of breast cancer, coronary heart disease, active liver disease, unexplained vaginal bleeding, high-risk endometrial cancer, transient ischemic attack, and a previous venous thromboembolic event or stroke.

“Fortunately, we have things in development,” Dr. Faubion said. She reviewed a wide range of therapies that are not currently Food and Drug Administration approved for vasomotor symptoms but are either available off label or are in clinical trials.

One of these is oxybutynin, an antimuscarinic, anticholinergic agent currently used to treat overactive bladder and overactive sweating. In a 2016 trial, 73% of women taking 15 mg extended-release oxybutynin once daily rated their symptoms as “much better,” compared with 26% who received placebo. The women experienced reduced frequency and severity of hot flashes and better sleep.

Subsequent research found a 60% reduction in hot flash frequency with 2.5 mg twice a day and a 77% reduction with 5 mg twice a day, compared with a 27% reduction with placebo. The only reported side effect that occurred more often with oxybutynin was dry mouth, but there were no significant differences in reasons for discontinuation between the treatment and placebo groups.

There are, however, some potential long-term cognitive effects from oxybutynin, Dr. Faubion said. Some research has shown an increased risk of dementia from oxybutynin and from an overall higher cumulative use of anticholinergics.

“There’s some concern about that for long-term use,” she said, but it’s effective, it’s “probably not harmful [when] used short term in women with significant, bothersome hot flashes who are unwilling or unable to use hormone therapy, and the adverse effects are tolerable for most women.” Women with bladder symptoms would be especially ideal candidates since the drug already treats those.

Dr. Faubion then discussed a new estrogen called estetrol (E4), a naturally occurring estrogen with selection action in tissues that is produced by the fetal liver and crosses the placenta. It has a long half-life of 28-32 hours, and its potential mechanism may give it a different safety profile than estradiol (E2). “There may be a lower risk of drug-drug interactions; lower breast stimulation, pain or carcinogenic impact; lower impact on triglycerides; and a neutral impact on markers of coagulation,” she said.

Though estetrol was recently approved as an oral contraceptive under the name Estelle, it’s also under investigation as a postmenopausal regimen. Preliminary findings suggest it reduces vasomotor symptom severity by 44%, compared with 30% with placebo, at 15 mg, the apparent minimum effective dose. The safety profile showed no endometrial hyperplasia and no unexpected adverse events. In those taking 15 mg of estetrol, mean endometrial thickness increased from 2 to 6 mm but returned to baseline after progestin therapy.

“The 15-mg dose also positively influenced markers of bone turnover, increased HDL [cholesterol], improved glucose tolerance,” and had no effects on coagulation parameters or triglycerides, Dr. Faubion added.

Another group of potential agents being studied for hot flashes are NK3 antagonists, which aim to exploit the recent discovery that kisspeptin, neurokinin B, and dynorphin (KNDy) neurons may play an important role in the etiology of vasomotor symptoms. Development of one of these, MLE 4901, was halted despite a 45% reduction in hot flashes because 3 of 28 women developed transiently elevated liver function tests, about four to six times the upper limit of normal.

Two others, fezolinetant and NT-814, are in phase 2 trials and have shown a significant reduction in symptoms, compared with placebo. The most commonly reported adverse effect in the phase 2a trial was gastrointestinal effects, but none of the participants stopped the drug because of these, and no elevated liver tests occurred. In the larger phase 2b trial, the most commonly reported treatment-emergent adverse events included nausea, diarrhea, fatigue, urinary tract infection, sinusitis, upper respiratory infection, headache, and cough. Five women discontinued the drug because of elevated liver enzymes.

“Overall, NK3 inhibitors appear to be generally well tolerated,” Dr. Faubion said. “There does seem to be mild transaminase elevation,” though it’s not yet known if this is an effect from this class of drugs as a whole. She noted that follicle-stimulating hormone does not significantly increase, which is important because elevated FSH is associated with poor bone health, nor does estradiol significantly increase, which is clinically relevant for women at high risk of breast cancer.

“We don’t know the effects on the heart, the brain, the bone, mood, weight, or sexual health, so there’s a lot that is still not known,” Dr. Faubion said. “We still don’t know about long-term safety and efficacy with these chemical compounds,” but clinical trials of them are ongoing.

They “would be a welcome alternative to hormone therapy for those who can’t or prefer not to use a hormonal option,” Dr. Faubion said. “However, we may need broad education of clinicians to caution against widespread abandonment of hormone therapy, particularly in women with premature or early menopause.”

Donna Klassen, LCSW, the cofounder of Let’s Talk Menopause, asked whether any of these new therapies were being tested in women with breast cancer and whether anything was known about taking oxybutynin at the same time as letrozole.

“I suspect that most women with chronic diseases would have been excluded from these initial studies, but I can’t speak to that,” Dr. Faubion said, and she wasn’t aware of any data related to taking oxybutynin and letrozole concurrently.

James Simon, MD, medical director and founder of IntimMedicine and one of those who led the research on oxybutynin, responded that his trials excluded breast cancer survivors and anyone taking aromatase inhibitors.

“It will be unlikely that, in the very near future, that data will be available because all the clinical developments on these NK3s or KNDy neuron-modulating drugs exclude cancer patients,” Dr. Simon said.

However, another attendee, Lisa Larkin, MD, of Cincinnati, introduced herself as a breast cancer survivor who takes tamoxifen and said she feels “completely comfortable” prescribing oxybutynin to breast cancer survivors.

“In terms of side effects and effectiveness in patients on tamoxifen and aromatase inhibitors, I’ve had incredibly good luck with it, and I think it’s underutilized,” Dr. Larkin said. “The clinical pearl I would tell you is you can start really low, and the dry mouth really seems to improve with time.” She added that patients should be informed that it takes 2 weeks before it begins working, but the side effects eventually go away. “It becomes very tolerable, so I just encourage all of you to consider it as another great option.”

Dr. Faubion had no disclosures. Disclosure information was unavailable for Dr. Simon, Dr. Larkin, and Ms. Klassen.

Hot flashes affect three out of four women and can last 7-10 years, but the current standard of care treatment isn’t necessarily appropriate for all women who experience vasomotor symptoms, according to Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health Clinic in Jacksonville, Fla.

For the majority of women under age 60 who are within 10 years of menopause, hormone therapy currently remains the most effective management option for hot flashes where the benefits outweigh the risks, Dr. Faubion told attendees Sept. 25 during a plenary at the annual meeting of the North American Menopause Society. “But really, individualizing treatment is the goal, and there are some women who are going to need some other options.”

Contraindications for hormone therapy include having a history of breast cancer, coronary heart disease, active liver disease, unexplained vaginal bleeding, high-risk endometrial cancer, transient ischemic attack, and a previous venous thromboembolic event or stroke.

“Fortunately, we have things in development,” Dr. Faubion said. She reviewed a wide range of therapies that are not currently Food and Drug Administration approved for vasomotor symptoms but are either available off label or are in clinical trials.

One of these is oxybutynin, an antimuscarinic, anticholinergic agent currently used to treat overactive bladder and overactive sweating. In a 2016 trial, 73% of women taking 15 mg extended-release oxybutynin once daily rated their symptoms as “much better,” compared with 26% who received placebo. The women experienced reduced frequency and severity of hot flashes and better sleep.

Subsequent research found a 60% reduction in hot flash frequency with 2.5 mg twice a day and a 77% reduction with 5 mg twice a day, compared with a 27% reduction with placebo. The only reported side effect that occurred more often with oxybutynin was dry mouth, but there were no significant differences in reasons for discontinuation between the treatment and placebo groups.

There are, however, some potential long-term cognitive effects from oxybutynin, Dr. Faubion said. Some research has shown an increased risk of dementia from oxybutynin and from an overall higher cumulative use of anticholinergics.

“There’s some concern about that for long-term use,” she said, but it’s effective, it’s “probably not harmful [when] used short term in women with significant, bothersome hot flashes who are unwilling or unable to use hormone therapy, and the adverse effects are tolerable for most women.” Women with bladder symptoms would be especially ideal candidates since the drug already treats those.

Dr. Faubion then discussed a new estrogen called estetrol (E4), a naturally occurring estrogen with selection action in tissues that is produced by the fetal liver and crosses the placenta. It has a long half-life of 28-32 hours, and its potential mechanism may give it a different safety profile than estradiol (E2). “There may be a lower risk of drug-drug interactions; lower breast stimulation, pain or carcinogenic impact; lower impact on triglycerides; and a neutral impact on markers of coagulation,” she said.

Though estetrol was recently approved as an oral contraceptive under the name Estelle, it’s also under investigation as a postmenopausal regimen. Preliminary findings suggest it reduces vasomotor symptom severity by 44%, compared with 30% with placebo, at 15 mg, the apparent minimum effective dose. The safety profile showed no endometrial hyperplasia and no unexpected adverse events. In those taking 15 mg of estetrol, mean endometrial thickness increased from 2 to 6 mm but returned to baseline after progestin therapy.

“The 15-mg dose also positively influenced markers of bone turnover, increased HDL [cholesterol], improved glucose tolerance,” and had no effects on coagulation parameters or triglycerides, Dr. Faubion added.

Another group of potential agents being studied for hot flashes are NK3 antagonists, which aim to exploit the recent discovery that kisspeptin, neurokinin B, and dynorphin (KNDy) neurons may play an important role in the etiology of vasomotor symptoms. Development of one of these, MLE 4901, was halted despite a 45% reduction in hot flashes because 3 of 28 women developed transiently elevated liver function tests, about four to six times the upper limit of normal.

Two others, fezolinetant and NT-814, are in phase 2 trials and have shown a significant reduction in symptoms, compared with placebo. The most commonly reported adverse effect in the phase 2a trial was gastrointestinal effects, but none of the participants stopped the drug because of these, and no elevated liver tests occurred. In the larger phase 2b trial, the most commonly reported treatment-emergent adverse events included nausea, diarrhea, fatigue, urinary tract infection, sinusitis, upper respiratory infection, headache, and cough. Five women discontinued the drug because of elevated liver enzymes.

“Overall, NK3 inhibitors appear to be generally well tolerated,” Dr. Faubion said. “There does seem to be mild transaminase elevation,” though it’s not yet known if this is an effect from this class of drugs as a whole. She noted that follicle-stimulating hormone does not significantly increase, which is important because elevated FSH is associated with poor bone health, nor does estradiol significantly increase, which is clinically relevant for women at high risk of breast cancer.

“We don’t know the effects on the heart, the brain, the bone, mood, weight, or sexual health, so there’s a lot that is still not known,” Dr. Faubion said. “We still don’t know about long-term safety and efficacy with these chemical compounds,” but clinical trials of them are ongoing.

They “would be a welcome alternative to hormone therapy for those who can’t or prefer not to use a hormonal option,” Dr. Faubion said. “However, we may need broad education of clinicians to caution against widespread abandonment of hormone therapy, particularly in women with premature or early menopause.”

Donna Klassen, LCSW, the cofounder of Let’s Talk Menopause, asked whether any of these new therapies were being tested in women with breast cancer and whether anything was known about taking oxybutynin at the same time as letrozole.

“I suspect that most women with chronic diseases would have been excluded from these initial studies, but I can’t speak to that,” Dr. Faubion said, and she wasn’t aware of any data related to taking oxybutynin and letrozole concurrently.

James Simon, MD, medical director and founder of IntimMedicine and one of those who led the research on oxybutynin, responded that his trials excluded breast cancer survivors and anyone taking aromatase inhibitors.

“It will be unlikely that, in the very near future, that data will be available because all the clinical developments on these NK3s or KNDy neuron-modulating drugs exclude cancer patients,” Dr. Simon said.

However, another attendee, Lisa Larkin, MD, of Cincinnati, introduced herself as a breast cancer survivor who takes tamoxifen and said she feels “completely comfortable” prescribing oxybutynin to breast cancer survivors.

“In terms of side effects and effectiveness in patients on tamoxifen and aromatase inhibitors, I’ve had incredibly good luck with it, and I think it’s underutilized,” Dr. Larkin said. “The clinical pearl I would tell you is you can start really low, and the dry mouth really seems to improve with time.” She added that patients should be informed that it takes 2 weeks before it begins working, but the side effects eventually go away. “It becomes very tolerable, so I just encourage all of you to consider it as another great option.”

Dr. Faubion had no disclosures. Disclosure information was unavailable for Dr. Simon, Dr. Larkin, and Ms. Klassen.

Hot flashes affect three out of four women and can last 7-10 years, but the current standard of care treatment isn’t necessarily appropriate for all women who experience vasomotor symptoms, according to Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health Clinic in Jacksonville, Fla.

For the majority of women under age 60 who are within 10 years of menopause, hormone therapy currently remains the most effective management option for hot flashes where the benefits outweigh the risks, Dr. Faubion told attendees Sept. 25 during a plenary at the annual meeting of the North American Menopause Society. “But really, individualizing treatment is the goal, and there are some women who are going to need some other options.”

Contraindications for hormone therapy include having a history of breast cancer, coronary heart disease, active liver disease, unexplained vaginal bleeding, high-risk endometrial cancer, transient ischemic attack, and a previous venous thromboembolic event or stroke.

“Fortunately, we have things in development,” Dr. Faubion said. She reviewed a wide range of therapies that are not currently Food and Drug Administration approved for vasomotor symptoms but are either available off label or are in clinical trials.

One of these is oxybutynin, an antimuscarinic, anticholinergic agent currently used to treat overactive bladder and overactive sweating. In a 2016 trial, 73% of women taking 15 mg extended-release oxybutynin once daily rated their symptoms as “much better,” compared with 26% who received placebo. The women experienced reduced frequency and severity of hot flashes and better sleep.

Subsequent research found a 60% reduction in hot flash frequency with 2.5 mg twice a day and a 77% reduction with 5 mg twice a day, compared with a 27% reduction with placebo. The only reported side effect that occurred more often with oxybutynin was dry mouth, but there were no significant differences in reasons for discontinuation between the treatment and placebo groups.

There are, however, some potential long-term cognitive effects from oxybutynin, Dr. Faubion said. Some research has shown an increased risk of dementia from oxybutynin and from an overall higher cumulative use of anticholinergics.

“There’s some concern about that for long-term use,” she said, but it’s effective, it’s “probably not harmful [when] used short term in women with significant, bothersome hot flashes who are unwilling or unable to use hormone therapy, and the adverse effects are tolerable for most women.” Women with bladder symptoms would be especially ideal candidates since the drug already treats those.

Dr. Faubion then discussed a new estrogen called estetrol (E4), a naturally occurring estrogen with selection action in tissues that is produced by the fetal liver and crosses the placenta. It has a long half-life of 28-32 hours, and its potential mechanism may give it a different safety profile than estradiol (E2). “There may be a lower risk of drug-drug interactions; lower breast stimulation, pain or carcinogenic impact; lower impact on triglycerides; and a neutral impact on markers of coagulation,” she said.

Though estetrol was recently approved as an oral contraceptive under the name Estelle, it’s also under investigation as a postmenopausal regimen. Preliminary findings suggest it reduces vasomotor symptom severity by 44%, compared with 30% with placebo, at 15 mg, the apparent minimum effective dose. The safety profile showed no endometrial hyperplasia and no unexpected adverse events. In those taking 15 mg of estetrol, mean endometrial thickness increased from 2 to 6 mm but returned to baseline after progestin therapy.

“The 15-mg dose also positively influenced markers of bone turnover, increased HDL [cholesterol], improved glucose tolerance,” and had no effects on coagulation parameters or triglycerides, Dr. Faubion added.

Another group of potential agents being studied for hot flashes are NK3 antagonists, which aim to exploit the recent discovery that kisspeptin, neurokinin B, and dynorphin (KNDy) neurons may play an important role in the etiology of vasomotor symptoms. Development of one of these, MLE 4901, was halted despite a 45% reduction in hot flashes because 3 of 28 women developed transiently elevated liver function tests, about four to six times the upper limit of normal.

Two others, fezolinetant and NT-814, are in phase 2 trials and have shown a significant reduction in symptoms, compared with placebo. The most commonly reported adverse effect in the phase 2a trial was gastrointestinal effects, but none of the participants stopped the drug because of these, and no elevated liver tests occurred. In the larger phase 2b trial, the most commonly reported treatment-emergent adverse events included nausea, diarrhea, fatigue, urinary tract infection, sinusitis, upper respiratory infection, headache, and cough. Five women discontinued the drug because of elevated liver enzymes.

“Overall, NK3 inhibitors appear to be generally well tolerated,” Dr. Faubion said. “There does seem to be mild transaminase elevation,” though it’s not yet known if this is an effect from this class of drugs as a whole. She noted that follicle-stimulating hormone does not significantly increase, which is important because elevated FSH is associated with poor bone health, nor does estradiol significantly increase, which is clinically relevant for women at high risk of breast cancer.

“We don’t know the effects on the heart, the brain, the bone, mood, weight, or sexual health, so there’s a lot that is still not known,” Dr. Faubion said. “We still don’t know about long-term safety and efficacy with these chemical compounds,” but clinical trials of them are ongoing.

They “would be a welcome alternative to hormone therapy for those who can’t or prefer not to use a hormonal option,” Dr. Faubion said. “However, we may need broad education of clinicians to caution against widespread abandonment of hormone therapy, particularly in women with premature or early menopause.”

Donna Klassen, LCSW, the cofounder of Let’s Talk Menopause, asked whether any of these new therapies were being tested in women with breast cancer and whether anything was known about taking oxybutynin at the same time as letrozole.

“I suspect that most women with chronic diseases would have been excluded from these initial studies, but I can’t speak to that,” Dr. Faubion said, and she wasn’t aware of any data related to taking oxybutynin and letrozole concurrently.

James Simon, MD, medical director and founder of IntimMedicine and one of those who led the research on oxybutynin, responded that his trials excluded breast cancer survivors and anyone taking aromatase inhibitors.

“It will be unlikely that, in the very near future, that data will be available because all the clinical developments on these NK3s or KNDy neuron-modulating drugs exclude cancer patients,” Dr. Simon said.

However, another attendee, Lisa Larkin, MD, of Cincinnati, introduced herself as a breast cancer survivor who takes tamoxifen and said she feels “completely comfortable” prescribing oxybutynin to breast cancer survivors.

“In terms of side effects and effectiveness in patients on tamoxifen and aromatase inhibitors, I’ve had incredibly good luck with it, and I think it’s underutilized,” Dr. Larkin said. “The clinical pearl I would tell you is you can start really low, and the dry mouth really seems to improve with time.” She added that patients should be informed that it takes 2 weeks before it begins working, but the side effects eventually go away. “It becomes very tolerable, so I just encourage all of you to consider it as another great option.”

Dr. Faubion had no disclosures. Disclosure information was unavailable for Dr. Simon, Dr. Larkin, and Ms. Klassen.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

A version of this article first appeared on WebMD.com.

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

A version of this article first appeared on WebMD.com.

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

A version of this article first appeared on WebMD.com.

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

A version of this article first appeared on WebMD.com.

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

A version of this article first appeared on Medscape.com.

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

A version of this article first appeared on Medscape.com.

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

A version of this article first appeared on Medscape.com.