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Fed Pract
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gaming
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
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Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
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pedophilia
poker
porn
pornography
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recreational drug
sex slave rings
slot machine
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Texas hold 'em
UFC
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bunges
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butt
butt fuck
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buttfucked
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cock sucker
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.

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Open Clinical Trials for Patients With Chronic Obstructive Pulmonary Disease

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Changed
Wed, 02/26/2025 - 09:46

The clinical trials listed below are open as of February 21, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Actively Recruiting

The Effect of Interval Exercise on Functional Outcomes in Veterans With COPD and OSA

The term overlap syndrome (OS) is used to describe the presence of both COPD and obstructive sleep apnea (OSA) in a single patient. Due to premature aging, patients with OS are prone to developing functional decline up to 20 years earlier than the general population. The International Classification of Functioning, Disability and Health (ICF) evaluates functional status in chronic pulmonary disease globally in 5 domains. The investigators propose to study validated outcomes in 3 of these domains: (1) participation in life situations; (2) physical activity; and (3) cardiovascular health. The investigators’ long-term goal is to develop an exercise strategy tailored to veterans with OS which will reduce the risk of functional decline through increased physical activity.

ID: NCT05254431

Sponsor; Collaborator: VA Office of Research and Development; Madalina Macrea, MD, PhD

Location: Salem VA Medical Center, Virginia


 

The Development of an Integrated Physical Activity and Mental Health Intervention for Veterans With COPD, Emotion Distress, and Low Physical Activity

COPD is a prevalent and debilitating chronic disease in veterans. COPD is highly comorbid with depression and anxiety, conferring greater morbidity and mortality risk. Physical activity is a modifiable behavior that can improve COPD outcomes. However, to date, interventions targeting physical activity have not addressed the high comorbidity between COPD and depression and/or anxiety symptoms (emotional distress) despite emotional distress predicting poorer response to physical activity interventions. This CDA-2 proposal will develop and test the acceptability and feasibility of an integrative physical activity and mental health intervention for veterans with COPD, emotional distress, and low physical activity. The intervention will be delivered via VA Video Connect enabling access to care among veterans with substantial barriers to hospital-based outpatient care.

ID: NCT04953806

Sponsor; Collaborator: VA Office of Research and Development; Patricia Bamonti, PhD

Location: VA Boston Healthcare System, Jamaica Plain Campus


 

Neurocognitive and Health Impact of Sleep Apnea in Elderly Veterans With Comorbid COPD

Cognitive dysfunction in the aging veteran population is a growing health concern in the Veterans Health System. It is not known whether OSA coexisting with COPD will enhance the risk for cognitive dysfunction. The investigators sought to investigate whether these two highly prevalent diseases that often coexist as 'overlap syndrome' combine to enhance cognitive impairment in the elderly veteran population. Thus, the investigators will study whether elderly patients with overlap syndrome have increased cognitive deficits compared with OSA or COPD alone. Additionally, treatment of OSA with positive airway pressure (PAP) has been shown to improve neurocognitive function in moderate-to-severe OSA while cognitive decline in COPD may be reversible through treatment with long-term oxygen therapy. The investigators will also study whether treatment with PAP and supplemental oxygen vs PAP alone will improve cognitive function and improve quality of life of elderly veterans.

ID: NCT02703207

Sponsor; Investigators: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations:  John D. Dingell VA Medical Center, Detroit


 

The Effect of a Technology-Mediated Integrated Walking and Tai Chi Intervention on Physical Function in Veterans With COPD and Chronic Musculoskeletal Pain (WATCH for Pain)

Persons with COPD benefit from being physically active, but they are often limited by chronic musculoskeletal pain. This project will determine whether a non-pharmacologic, integrated, technology-mediated walking and tai chi mindfulness intervention can improve physical function in veterans with COPD and chronic musculoskeletal pain. The proposed research addresses VA Rehabilitation R&D Service's high priority area of improving health-related quality of life by reducing disease burden and maximizing function in veterans with chronic disease.

ID: NCT05701982

Sponsor; Investigator: VA Office of Research and Development; Marilyn L. Moy, MD; University of Michigan, Beth Israel Deaconess Medical Center

Location: VA Boston Healthcare System


 

Internet-based Cognitive-behavioral Treatment for Insomnia in COPD Patients Undergoing Pulmonary Rehabilitation

This study is a randomized controlled trial (RCT) to compare sleep and health-related functioning in veterans with COPD and insomnia receiving an Internet-based behavioral treatment for insomnia vs online insomnia patient education. Participants will undergo a sleep and health assessment that will be performed at baseline, post-treatment, and 3 months later. Participants will be randomly assigned to either Internet-based behavioral treatment for insomnia or online insomnia patient education.

ID: NCT04700098

Sponsor; Collaborators: VA Office of Research and Development; Faith S. Luyster, PhD

Locations: VA Pittsburgh Healthcare System; John D. Dingell VA Medical Center, Detroit


Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH (BETTER COPD-PH)

The investigators will study whether the drug tadalafil improves shortness of breath in 126 veterans with COPD and high blood pressure in the lungs. The investigators will also assess whether tadalafil improves quality of life, home daily physical activity, exercise endurance, the frequency of acute flares of COPD, blood pressure in the lungs, and lung function. Veterans who enroll in the trial will be allocated by chance to either active tadalafil or an inactive identical capsule (placebo). Neither the veteran nor the investigator will know whether the veteran is taking tadalafil or placebo. Veterans will be followed closely in clinic or by telephone at 1, 2, 3, 4, 5, and 6 months, with attention to side effects and safety. At 1,3, and 6 months the investigators will repeat the questionnaires and testing of blood pressures in the lung and lung function. The investigators anticipate that the results of this study will determine whether tadalafil improves shortness of breath when added to usual medications for COPD.

ID: NCT05937854

Sponsor; Collaborator: VA Office of Research and Development; Sharon I. Rounds, MD

Locations: Rocky Mountain Regional VA Medical Center, Colorado; Joseph Maxwell Cleland Atlanta VA Medical Center ; VA Boston Healthcare System Jamaica Plain Campus; VA Nebraska-Western Iowa Health Care System; Providence VA Medical Center


 

Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans With Chronic Obstructive Pulmonary Disease and Comorbid Obstructive Sleep Apnea (Overlap Syndrome)

Obstructive sleep apnea (OSA) and COPD are highly prevalent chronic respiratory diseases in the veteran population. OSA co-occurring with COPD, known as overlap syndrome (OVS), is a complex chronic medical condition associated with grave consequences. OVS is highly prevalent in veterans. Veterans with OVS may be at increased risk for cognitive deficits, poor sleep quality as well as a reduced quality of life (QoL). The overall objective is to study the effects of positive airway pressure therapy on clinical outcomes in patients with OVS.

ID: NCT04179981

Sponsor; Investigator: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations: VA Ann Arbor Healthcare System; John D. Dingell VA Medical Center, Detroit


 

Developing an Intervention to Optimize Virtual Care Adoption for COPD Management (VC-OPTIONS)

VA is a leader in virtual care (VC), including the patient portal, mobile apps, and telehealth programs. VC has great utility for managing chronic conditions like COPD. However, adoption of many VC services has been slow. Lack of awareness about these services is one of the most prominent patient- and health care team-facing barriers to adopting VC. This study will develop, refine, and pilot a stakeholder-informed multicomponent implementation strategy to support adoption of VC, referred to as VC-OPTIONS (Virtual Care for Chronic Obstructive Pulmonary Disease Adoption Support). This feasibility trial will pilot the VC-OPTIONS implementation strategy to assess feasibility and acceptability and gather preliminary effectiveness data to inform a larger hybrid effectiveness-implementation trial. The core component of VC-OPTIONS will be the provision of information via VA's Annie texting program to empower patients with knowledge about the array of VC services and how they can be used to support COPD management. It is hypothesized that this strategy will be acceptable and feasible. This work will improve patient and team awareness of and communication about VC services, and support patient access to VC services for COPD management.

ID: NCT05986214

Sponsor; Collaborators: VA Office of Research and Development; Stephanie Robinson, PhD

Location: VA Bedford Healthcare System, Massachusetts; VA Boston Healthcare System Jamaica Plain Campus


Chronic Lung Disease and COVID-19: Understanding Severity, Recovery and Rehabilitation Needs (LAUREL)

This study is comprised of 3 approaches. First, the investigators will conduct a retrospective cohort study to determine factors associated with COVID-19 severity and complications and understand COVID-19 outcomes, including all-cause mortality, postdischarge events, and impacts of rehabilitation services (third aim). The second aim is a mixed-method study and follows COVID-19 patients with repeated surveys to determine patient-reported functional outcomes, health recovery, and rehabilitation needs after COVID-19. The investigators will recruit patients and their informal caregivers for interviews to assess their function and rehabilitation needs.

ID: NCT04628039

Sponsor; Collaborators: VA Office of Research and Development; Kristina A. Crothers, MD

Locations: VA Ann Arbor Healthcare System; VA Puget Sound Health Care System, Washington


 

Accessing Mobility Using Wearable Sensors

This study will examine whether wearable sensors can be used to track changes in cognitive-motor performance in response to a disease or an intervention. The investigators specific aims are twofold, first aim to explore whether and how a clinical condition such as chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) may impact motor-cognitive performance measurable using validated wearable devices (eg, LEGSys, BalanSENS, and Frailty Meter). Second, the investigators will explore whether an exercise intervention provided via telemedicine (telerehabilitation) can enhance motor-cognitive performance.

ID: NCT04306588

Sponsor; Collaborators: Baylor College of Medicine, Bijan Najafi, PhD

Locations: Michael E. DeBakey Veterans Affairs Medical Center, Houston

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The clinical trials listed below are open as of February 21, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Actively Recruiting

The Effect of Interval Exercise on Functional Outcomes in Veterans With COPD and OSA

The term overlap syndrome (OS) is used to describe the presence of both COPD and obstructive sleep apnea (OSA) in a single patient. Due to premature aging, patients with OS are prone to developing functional decline up to 20 years earlier than the general population. The International Classification of Functioning, Disability and Health (ICF) evaluates functional status in chronic pulmonary disease globally in 5 domains. The investigators propose to study validated outcomes in 3 of these domains: (1) participation in life situations; (2) physical activity; and (3) cardiovascular health. The investigators’ long-term goal is to develop an exercise strategy tailored to veterans with OS which will reduce the risk of functional decline through increased physical activity.

ID: NCT05254431

Sponsor; Collaborator: VA Office of Research and Development; Madalina Macrea, MD, PhD

Location: Salem VA Medical Center, Virginia


 

The Development of an Integrated Physical Activity and Mental Health Intervention for Veterans With COPD, Emotion Distress, and Low Physical Activity

COPD is a prevalent and debilitating chronic disease in veterans. COPD is highly comorbid with depression and anxiety, conferring greater morbidity and mortality risk. Physical activity is a modifiable behavior that can improve COPD outcomes. However, to date, interventions targeting physical activity have not addressed the high comorbidity between COPD and depression and/or anxiety symptoms (emotional distress) despite emotional distress predicting poorer response to physical activity interventions. This CDA-2 proposal will develop and test the acceptability and feasibility of an integrative physical activity and mental health intervention for veterans with COPD, emotional distress, and low physical activity. The intervention will be delivered via VA Video Connect enabling access to care among veterans with substantial barriers to hospital-based outpatient care.

ID: NCT04953806

Sponsor; Collaborator: VA Office of Research and Development; Patricia Bamonti, PhD

Location: VA Boston Healthcare System, Jamaica Plain Campus


 

Neurocognitive and Health Impact of Sleep Apnea in Elderly Veterans With Comorbid COPD

Cognitive dysfunction in the aging veteran population is a growing health concern in the Veterans Health System. It is not known whether OSA coexisting with COPD will enhance the risk for cognitive dysfunction. The investigators sought to investigate whether these two highly prevalent diseases that often coexist as 'overlap syndrome' combine to enhance cognitive impairment in the elderly veteran population. Thus, the investigators will study whether elderly patients with overlap syndrome have increased cognitive deficits compared with OSA or COPD alone. Additionally, treatment of OSA with positive airway pressure (PAP) has been shown to improve neurocognitive function in moderate-to-severe OSA while cognitive decline in COPD may be reversible through treatment with long-term oxygen therapy. The investigators will also study whether treatment with PAP and supplemental oxygen vs PAP alone will improve cognitive function and improve quality of life of elderly veterans.

ID: NCT02703207

Sponsor; Investigators: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations:  John D. Dingell VA Medical Center, Detroit


 

The Effect of a Technology-Mediated Integrated Walking and Tai Chi Intervention on Physical Function in Veterans With COPD and Chronic Musculoskeletal Pain (WATCH for Pain)

Persons with COPD benefit from being physically active, but they are often limited by chronic musculoskeletal pain. This project will determine whether a non-pharmacologic, integrated, technology-mediated walking and tai chi mindfulness intervention can improve physical function in veterans with COPD and chronic musculoskeletal pain. The proposed research addresses VA Rehabilitation R&D Service's high priority area of improving health-related quality of life by reducing disease burden and maximizing function in veterans with chronic disease.

ID: NCT05701982

Sponsor; Investigator: VA Office of Research and Development; Marilyn L. Moy, MD; University of Michigan, Beth Israel Deaconess Medical Center

Location: VA Boston Healthcare System


 

Internet-based Cognitive-behavioral Treatment for Insomnia in COPD Patients Undergoing Pulmonary Rehabilitation

This study is a randomized controlled trial (RCT) to compare sleep and health-related functioning in veterans with COPD and insomnia receiving an Internet-based behavioral treatment for insomnia vs online insomnia patient education. Participants will undergo a sleep and health assessment that will be performed at baseline, post-treatment, and 3 months later. Participants will be randomly assigned to either Internet-based behavioral treatment for insomnia or online insomnia patient education.

ID: NCT04700098

Sponsor; Collaborators: VA Office of Research and Development; Faith S. Luyster, PhD

Locations: VA Pittsburgh Healthcare System; John D. Dingell VA Medical Center, Detroit


Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH (BETTER COPD-PH)

The investigators will study whether the drug tadalafil improves shortness of breath in 126 veterans with COPD and high blood pressure in the lungs. The investigators will also assess whether tadalafil improves quality of life, home daily physical activity, exercise endurance, the frequency of acute flares of COPD, blood pressure in the lungs, and lung function. Veterans who enroll in the trial will be allocated by chance to either active tadalafil or an inactive identical capsule (placebo). Neither the veteran nor the investigator will know whether the veteran is taking tadalafil or placebo. Veterans will be followed closely in clinic or by telephone at 1, 2, 3, 4, 5, and 6 months, with attention to side effects and safety. At 1,3, and 6 months the investigators will repeat the questionnaires and testing of blood pressures in the lung and lung function. The investigators anticipate that the results of this study will determine whether tadalafil improves shortness of breath when added to usual medications for COPD.

ID: NCT05937854

Sponsor; Collaborator: VA Office of Research and Development; Sharon I. Rounds, MD

Locations: Rocky Mountain Regional VA Medical Center, Colorado; Joseph Maxwell Cleland Atlanta VA Medical Center ; VA Boston Healthcare System Jamaica Plain Campus; VA Nebraska-Western Iowa Health Care System; Providence VA Medical Center


 

Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans With Chronic Obstructive Pulmonary Disease and Comorbid Obstructive Sleep Apnea (Overlap Syndrome)

Obstructive sleep apnea (OSA) and COPD are highly prevalent chronic respiratory diseases in the veteran population. OSA co-occurring with COPD, known as overlap syndrome (OVS), is a complex chronic medical condition associated with grave consequences. OVS is highly prevalent in veterans. Veterans with OVS may be at increased risk for cognitive deficits, poor sleep quality as well as a reduced quality of life (QoL). The overall objective is to study the effects of positive airway pressure therapy on clinical outcomes in patients with OVS.

ID: NCT04179981

Sponsor; Investigator: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations: VA Ann Arbor Healthcare System; John D. Dingell VA Medical Center, Detroit


 

Developing an Intervention to Optimize Virtual Care Adoption for COPD Management (VC-OPTIONS)

VA is a leader in virtual care (VC), including the patient portal, mobile apps, and telehealth programs. VC has great utility for managing chronic conditions like COPD. However, adoption of many VC services has been slow. Lack of awareness about these services is one of the most prominent patient- and health care team-facing barriers to adopting VC. This study will develop, refine, and pilot a stakeholder-informed multicomponent implementation strategy to support adoption of VC, referred to as VC-OPTIONS (Virtual Care for Chronic Obstructive Pulmonary Disease Adoption Support). This feasibility trial will pilot the VC-OPTIONS implementation strategy to assess feasibility and acceptability and gather preliminary effectiveness data to inform a larger hybrid effectiveness-implementation trial. The core component of VC-OPTIONS will be the provision of information via VA's Annie texting program to empower patients with knowledge about the array of VC services and how they can be used to support COPD management. It is hypothesized that this strategy will be acceptable and feasible. This work will improve patient and team awareness of and communication about VC services, and support patient access to VC services for COPD management.

ID: NCT05986214

Sponsor; Collaborators: VA Office of Research and Development; Stephanie Robinson, PhD

Location: VA Bedford Healthcare System, Massachusetts; VA Boston Healthcare System Jamaica Plain Campus


Chronic Lung Disease and COVID-19: Understanding Severity, Recovery and Rehabilitation Needs (LAUREL)

This study is comprised of 3 approaches. First, the investigators will conduct a retrospective cohort study to determine factors associated with COVID-19 severity and complications and understand COVID-19 outcomes, including all-cause mortality, postdischarge events, and impacts of rehabilitation services (third aim). The second aim is a mixed-method study and follows COVID-19 patients with repeated surveys to determine patient-reported functional outcomes, health recovery, and rehabilitation needs after COVID-19. The investigators will recruit patients and their informal caregivers for interviews to assess their function and rehabilitation needs.

ID: NCT04628039

Sponsor; Collaborators: VA Office of Research and Development; Kristina A. Crothers, MD

Locations: VA Ann Arbor Healthcare System; VA Puget Sound Health Care System, Washington


 

Accessing Mobility Using Wearable Sensors

This study will examine whether wearable sensors can be used to track changes in cognitive-motor performance in response to a disease or an intervention. The investigators specific aims are twofold, first aim to explore whether and how a clinical condition such as chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) may impact motor-cognitive performance measurable using validated wearable devices (eg, LEGSys, BalanSENS, and Frailty Meter). Second, the investigators will explore whether an exercise intervention provided via telemedicine (telerehabilitation) can enhance motor-cognitive performance.

ID: NCT04306588

Sponsor; Collaborators: Baylor College of Medicine, Bijan Najafi, PhD

Locations: Michael E. DeBakey Veterans Affairs Medical Center, Houston

The clinical trials listed below are open as of February 21, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Actively Recruiting

The Effect of Interval Exercise on Functional Outcomes in Veterans With COPD and OSA

The term overlap syndrome (OS) is used to describe the presence of both COPD and obstructive sleep apnea (OSA) in a single patient. Due to premature aging, patients with OS are prone to developing functional decline up to 20 years earlier than the general population. The International Classification of Functioning, Disability and Health (ICF) evaluates functional status in chronic pulmonary disease globally in 5 domains. The investigators propose to study validated outcomes in 3 of these domains: (1) participation in life situations; (2) physical activity; and (3) cardiovascular health. The investigators’ long-term goal is to develop an exercise strategy tailored to veterans with OS which will reduce the risk of functional decline through increased physical activity.

ID: NCT05254431

Sponsor; Collaborator: VA Office of Research and Development; Madalina Macrea, MD, PhD

Location: Salem VA Medical Center, Virginia


 

The Development of an Integrated Physical Activity and Mental Health Intervention for Veterans With COPD, Emotion Distress, and Low Physical Activity

COPD is a prevalent and debilitating chronic disease in veterans. COPD is highly comorbid with depression and anxiety, conferring greater morbidity and mortality risk. Physical activity is a modifiable behavior that can improve COPD outcomes. However, to date, interventions targeting physical activity have not addressed the high comorbidity between COPD and depression and/or anxiety symptoms (emotional distress) despite emotional distress predicting poorer response to physical activity interventions. This CDA-2 proposal will develop and test the acceptability and feasibility of an integrative physical activity and mental health intervention for veterans with COPD, emotional distress, and low physical activity. The intervention will be delivered via VA Video Connect enabling access to care among veterans with substantial barriers to hospital-based outpatient care.

ID: NCT04953806

Sponsor; Collaborator: VA Office of Research and Development; Patricia Bamonti, PhD

Location: VA Boston Healthcare System, Jamaica Plain Campus


 

Neurocognitive and Health Impact of Sleep Apnea in Elderly Veterans With Comorbid COPD

Cognitive dysfunction in the aging veteran population is a growing health concern in the Veterans Health System. It is not known whether OSA coexisting with COPD will enhance the risk for cognitive dysfunction. The investigators sought to investigate whether these two highly prevalent diseases that often coexist as 'overlap syndrome' combine to enhance cognitive impairment in the elderly veteran population. Thus, the investigators will study whether elderly patients with overlap syndrome have increased cognitive deficits compared with OSA or COPD alone. Additionally, treatment of OSA with positive airway pressure (PAP) has been shown to improve neurocognitive function in moderate-to-severe OSA while cognitive decline in COPD may be reversible through treatment with long-term oxygen therapy. The investigators will also study whether treatment with PAP and supplemental oxygen vs PAP alone will improve cognitive function and improve quality of life of elderly veterans.

ID: NCT02703207

Sponsor; Investigators: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations:  John D. Dingell VA Medical Center, Detroit


 

The Effect of a Technology-Mediated Integrated Walking and Tai Chi Intervention on Physical Function in Veterans With COPD and Chronic Musculoskeletal Pain (WATCH for Pain)

Persons with COPD benefit from being physically active, but they are often limited by chronic musculoskeletal pain. This project will determine whether a non-pharmacologic, integrated, technology-mediated walking and tai chi mindfulness intervention can improve physical function in veterans with COPD and chronic musculoskeletal pain. The proposed research addresses VA Rehabilitation R&D Service's high priority area of improving health-related quality of life by reducing disease burden and maximizing function in veterans with chronic disease.

ID: NCT05701982

Sponsor; Investigator: VA Office of Research and Development; Marilyn L. Moy, MD; University of Michigan, Beth Israel Deaconess Medical Center

Location: VA Boston Healthcare System


 

Internet-based Cognitive-behavioral Treatment for Insomnia in COPD Patients Undergoing Pulmonary Rehabilitation

This study is a randomized controlled trial (RCT) to compare sleep and health-related functioning in veterans with COPD and insomnia receiving an Internet-based behavioral treatment for insomnia vs online insomnia patient education. Participants will undergo a sleep and health assessment that will be performed at baseline, post-treatment, and 3 months later. Participants will be randomly assigned to either Internet-based behavioral treatment for insomnia or online insomnia patient education.

ID: NCT04700098

Sponsor; Collaborators: VA Office of Research and Development; Faith S. Luyster, PhD

Locations: VA Pittsburgh Healthcare System; John D. Dingell VA Medical Center, Detroit


Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH (BETTER COPD-PH)

The investigators will study whether the drug tadalafil improves shortness of breath in 126 veterans with COPD and high blood pressure in the lungs. The investigators will also assess whether tadalafil improves quality of life, home daily physical activity, exercise endurance, the frequency of acute flares of COPD, blood pressure in the lungs, and lung function. Veterans who enroll in the trial will be allocated by chance to either active tadalafil or an inactive identical capsule (placebo). Neither the veteran nor the investigator will know whether the veteran is taking tadalafil or placebo. Veterans will be followed closely in clinic or by telephone at 1, 2, 3, 4, 5, and 6 months, with attention to side effects and safety. At 1,3, and 6 months the investigators will repeat the questionnaires and testing of blood pressures in the lung and lung function. The investigators anticipate that the results of this study will determine whether tadalafil improves shortness of breath when added to usual medications for COPD.

ID: NCT05937854

Sponsor; Collaborator: VA Office of Research and Development; Sharon I. Rounds, MD

Locations: Rocky Mountain Regional VA Medical Center, Colorado; Joseph Maxwell Cleland Atlanta VA Medical Center ; VA Boston Healthcare System Jamaica Plain Campus; VA Nebraska-Western Iowa Health Care System; Providence VA Medical Center


 

Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans With Chronic Obstructive Pulmonary Disease and Comorbid Obstructive Sleep Apnea (Overlap Syndrome)

Obstructive sleep apnea (OSA) and COPD are highly prevalent chronic respiratory diseases in the veteran population. OSA co-occurring with COPD, known as overlap syndrome (OVS), is a complex chronic medical condition associated with grave consequences. OVS is highly prevalent in veterans. Veterans with OVS may be at increased risk for cognitive deficits, poor sleep quality as well as a reduced quality of life (QoL). The overall objective is to study the effects of positive airway pressure therapy on clinical outcomes in patients with OVS.

ID: NCT04179981

Sponsor; Investigator: VA Office of Research and Development; Susmita Chowdhuri, MD, MS

Locations: VA Ann Arbor Healthcare System; John D. Dingell VA Medical Center, Detroit


 

Developing an Intervention to Optimize Virtual Care Adoption for COPD Management (VC-OPTIONS)

VA is a leader in virtual care (VC), including the patient portal, mobile apps, and telehealth programs. VC has great utility for managing chronic conditions like COPD. However, adoption of many VC services has been slow. Lack of awareness about these services is one of the most prominent patient- and health care team-facing barriers to adopting VC. This study will develop, refine, and pilot a stakeholder-informed multicomponent implementation strategy to support adoption of VC, referred to as VC-OPTIONS (Virtual Care for Chronic Obstructive Pulmonary Disease Adoption Support). This feasibility trial will pilot the VC-OPTIONS implementation strategy to assess feasibility and acceptability and gather preliminary effectiveness data to inform a larger hybrid effectiveness-implementation trial. The core component of VC-OPTIONS will be the provision of information via VA's Annie texting program to empower patients with knowledge about the array of VC services and how they can be used to support COPD management. It is hypothesized that this strategy will be acceptable and feasible. This work will improve patient and team awareness of and communication about VC services, and support patient access to VC services for COPD management.

ID: NCT05986214

Sponsor; Collaborators: VA Office of Research and Development; Stephanie Robinson, PhD

Location: VA Bedford Healthcare System, Massachusetts; VA Boston Healthcare System Jamaica Plain Campus


Chronic Lung Disease and COVID-19: Understanding Severity, Recovery and Rehabilitation Needs (LAUREL)

This study is comprised of 3 approaches. First, the investigators will conduct a retrospective cohort study to determine factors associated with COVID-19 severity and complications and understand COVID-19 outcomes, including all-cause mortality, postdischarge events, and impacts of rehabilitation services (third aim). The second aim is a mixed-method study and follows COVID-19 patients with repeated surveys to determine patient-reported functional outcomes, health recovery, and rehabilitation needs after COVID-19. The investigators will recruit patients and their informal caregivers for interviews to assess their function and rehabilitation needs.

ID: NCT04628039

Sponsor; Collaborators: VA Office of Research and Development; Kristina A. Crothers, MD

Locations: VA Ann Arbor Healthcare System; VA Puget Sound Health Care System, Washington


 

Accessing Mobility Using Wearable Sensors

This study will examine whether wearable sensors can be used to track changes in cognitive-motor performance in response to a disease or an intervention. The investigators specific aims are twofold, first aim to explore whether and how a clinical condition such as chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) may impact motor-cognitive performance measurable using validated wearable devices (eg, LEGSys, BalanSENS, and Frailty Meter). Second, the investigators will explore whether an exercise intervention provided via telemedicine (telerehabilitation) can enhance motor-cognitive performance.

ID: NCT04306588

Sponsor; Collaborators: Baylor College of Medicine, Bijan Najafi, PhD

Locations: Michael E. DeBakey Veterans Affairs Medical Center, Houston

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Patients With Asthma and COPD At Increased Cancer Risk From Microplastics

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Mon, 02/24/2025 - 12:09

Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.

Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues. 

In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.

The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls. 

In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.

“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.

The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.

However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.

 

Current and Future Implications

The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said. 

“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.

“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.

More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.

The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.

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

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Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.

Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues. 

In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.

The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls. 

In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.

“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.

The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.

However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.

 

Current and Future Implications

The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said. 

“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.

“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.

More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.

The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.

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

Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.

Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues. 

In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.

The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls. 

In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.

“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.

The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.

However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.

 

Current and Future Implications

The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said. 

“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.

“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.

More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.

The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.

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

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A Veteran Presenting With Symptomatic Postprandial Episodes

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A Veteran Presenting With Symptomatic Postprandial Episodes

Idiopathic postprandial syndrome (IPP), initially termed reactive hypoglycemia, presents with hypoglycemic-like symptoms in the absence of biochemical hypoglycemia and remains a diagnosis of exclusion. Its pathophysiology is poorly understood. The diagnosis requires thorough evaluation of cardiac, metabolic, neurologic, and gastrointestinal causes, as well as Whipple triad criteria. Dietary modifications, including reduced carbohydrate intake, increased protein and fiber, and frequent small meals, remain the cornerstone of IPP management. Continuous glucose monitoring (CGM) may be a useful adjunct in correlating symptoms with glucose trends, but its role is still evolving.

In the evaluation of patients with symptoms suggestive of hypoglycemia (Figure 1), patients should first be assessed for Whipple triad: symptoms consistent with hypoglycemia, blood glucose level < 55 mg/dL, and reversal of symptoms with glucose.1 Patients who meet Whipple triad criteria should be investigated to identify further etiologies of hypoglycemia. They may include insulinoma, medication-induced (insulin, sulfonylurea, meglitinide, or β blocker use), postbariatric surgery complications, noninsulinoma pancreatogenous hypoglycemia syndrome, ackee fruit consumption, or familial conditions.2 The presence of hypoglycemic symptoms in the postprandial or fasting state can provide valuable insights into underlying etiology. 

Patients who do not meet Whipple triad criteria, but exhibit postprandial symptoms consistent with hypoglycemia, as in this case, present a diagnostic dilemma. IPP is defined as hypoglycemic symptoms occuring after carbohydrate ingestion without biochemical hypoglycemia. Initially termed reactive hypoglycemia, it was renamed in 1981to reflect the absence of low blood glucose levels.3

The understanding of this diagnosis has not significantly progressed since the 1980s. Its prevalence, incidence, risk factors, and societal burden remain unclear. IPP is a challenging diagnosis due to nonspecific symptoms that overlap with a myriad of conditions. These symptoms may include adrenergic symptoms such as diaphoresis, tremulousness, palpitations, anxiety, and hunger. Potentially severe neuroglycopenic symptoms, including weakness, dizziness, behavior changes, confusion, and coma, are not typically observed.4 Given that objective criteria are not well established, IPP remains a diagnosis of exclusion. It is imperative to rule out alternative etiologies, particularly cardiac, gastrointestinal, and neurologic causes.

CASE PRESENTATION

A male aged 41 years presented to primary care for evaluation of acute on chronic symptomatic postprandial episodes. He reported a history of symptomatic sinus bradycardia in the setting of sick sinus syndrome following dual-chamber pacemaker placement, posttraumatic stress disorder, and gastroesophageal reflux disease. He was a retired Navy sailor without any known occupational exposures who worked in the real estate industry. The patient reported feeling lightheaded, tremulous, and anxious most afternoons after lunch for several years. He also reported that meals heavy in carbohydrates exacerbated his symptoms, whereas skipping meals or lying down alleviated his symptoms. The patient also reported concomitant arm numbness, shortness of breath, palpitations, and nausea during these episodes. Review of systems was otherwise negative, including no weight changes, fever, chills, night sweats, chest pain, or syncope.

The patient’s medications included ferrous sulfate 325 mg once every other day, bupropion 200 mg once daily, metoprolol succinate 25 mg once daily, and as-needed lorazepam 1 mg once daily. The patient reported no current substance use but reported previous tobacco use 3 years prior (maximum 1 pack/week) and alcohol use 5 years prior (750 ml/day for 15 years). The patient did not exercise and typically ate oatmeal for breakfast, a sandwich or salad for lunch, and taquitos or salad for dinner, with snacks throughout the day. Notable family history included a maternal grandmother with colon cancer. The patient’s vital signs included a 36.8 °C temperature, heart rate 87 beats/min, 118/71 mm Hg blood pressure, oxygen saturation 98% on room air, 125.2 kg weight, and 38.5 body mass index. There were no orthostatic vital sign changes. A physical examination demonstrated obesity with an unremarkable cardiopulmonary and volume examination. 

Additional testing included Gallium-68 dototate positron emission tomography/computed tomography, brain magnetic resonance imaging, echocardiogram, electromyogram, exercise tolerance test, Holter monitoring, invasive cardiopulmonary exercise testing, pacemaker interrogation, pulmonary function testing, stress echocardiogram, tilt table test, and venogram computed tomography of the chest, but the results were unremarkable (Appendix). His afternoon nonfasting glucose level was 138 mg/dL with a concurrent hemoglobin A1c of 5.2%. The patient had a fasting C-peptide level of 3.7 ng/mL (reference range 0.5-2.0 ng/mL), fasting insulin level 19.1 mIU/L (reference range < 25 mIU/L), and a fasting glucose level of 93 mg/dL (reference range 70-99 mg/dL). The patient’s urine 5-HIAA, plasma metanephrines, urine metanephrines, insulin-like growth factor 1, prolactin, corticotropin, fasting cortisol, and thyrotropin yielded results within reference ranges (Table). The veteran was prescribed a CGM, which demonstrated normal glucose levels (≥ 55 mg/dL) during symptomatic episodes (Figure 2).



The patient was diagnosed with IPP given normoglycemia, exclusion of alternative diagnoses, and symptomatic improvement with dietary changes. He was referred to a nutritionist for a high-protein, high-fiber, and low-carbohydrate diet.

DISCUSSION

Seemingly simple diagnostic tools can lead to diagnostic pitfalls. Home glucose monitoring with the use of a standard glucometer during an episode is the typical first step in identifying hypoglycemia, as it is both pragmatic and accurate, with a mean absolute relative difference (MARD) of about 10% in hypoglycemic ranges.5 While the advent of CGM provides real-time data and can reveal clinically relevant fluctuations, it reveals mild hypoglycemia (54 to 70 mg/dL) of no clinical significance in a large proportion of individuals.

Additionally, CGM is less accurate than glucometers with a MARD of about 20% in hypoglycemia ranges.6 CGM technology, however, is rapidly evolving and undergoing further investigation for hypoglycemia detection. Therefore, CGM may be considered in select patients as prospective study results are established; the newest CGMs have MARDs very similar to fingerstick blood glucose data.7,8 In the patient described in this case, CGM helped corroborate the diagnosis, given that symptomatic episodes correlated with lower glucose levels. Provocative testing with oral glucose tolerance testing can frequently result in false positive hypoglycemic readings and is not recommended.9 Supervised mixed meal testing can also be used, which entails monitoring after consuming a mixed macronutrient meal. The test concludes after hypoglycemic symptoms develop or 5 hours elapse, whichever occurs first.1

 

The pathophysiology of IPP is poorly understood. Proposed mechanisms include increased insulin sensitivity, increased adrenergic sensitivity, impaired glucagon regulation, emotional distress, insulin resistance, and increased glucagon-like peptide-1 production.10-13 Research suggests this may occur as pancreatic β cells fail in early type 2 diabetes mellitus, with diminished first-phase insulin release leading to an initial exuberant rise in blood glucose, an overshooting of the second phase of insulin secretion, and the feeling of the postprandial blood glucose falling, even though the final glucose level achieved is not truly low.13 There are contradictory studies in the literature demonstrating no association between insulin resistance and hypoglycemic symptoms.14 In 2022, Kosuda and colleagues looked at homeostatic model assessment for insulin resistance in patients with postprandial syndrome. They found that the patients were slightly insulin resistant but had normal or exaggerated insulin secretory capacity compared to an oral glucose load, whereas glucagon levels were robustly suppressed by a glucose load. The observed hormonal responses may result in the glycemic patterns and symptoms observed; further study is warranted to elucidate the mechanism.15

Dietary modification is the cornerstone treatment for postprandial syndrome, including reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals. There is also evidence that a Mediterranean diet may be beneficial for managing hypoglycemic symptoms.16 Furthermore, α-glucosidase inhibitors, whose mechanism of action delays the digestion of carbohydrates, have demonstrated promise. This medication class has demonstrated significance in raising postprandial glucose levels and alleviating hypoglycemic symptoms in patients with true postprandial hypoglycemia.17

CONCLUSIONS

IPP is a benign diagnosis encompassing hypoglycemic symptoms without biochemical hypoglycemia. It is not a true hypoglycemic disorder. IPP is challenging to diagnose, given that it is an interpretation of exclusion, supported by symptom improvement with dietary changes (ie, reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals). Supervised mixed meal testing or CGM can be used to assist with diagnosis. Even though CGM is undergoing further study in this patient population, it corroborated the diagnosis in the patient described in this case.

For hypoglycemic symptoms, physicians should first assess for evidence of Whipple triad to evaluate for true biochemical hypoglycemia. For true hypoglycemia (< 55 mg/dL), physicians may conduct an examination in conjunction with an endocrinologist. For normoglycemia (≥ 55 mg/dL), physicians should first exclude alternative etiologies (including cardiac and neurologic), and subsequently consider IPP.

References
  1. Bansal N, Weinstock RS. Non-Diabetic Hypoglycemia. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext. MDText.com, Inc.; 2000.

  2. Service FJ. Hypoglycemic disorders. New Engl J Med. 1995;332(17):1144-1152.doi:10.1056/NEJM199504273321707

  3. Charles MA, Hofeldt F, Shackelford A, et al. Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals. Diabetes. 1981;30(6):465-470.

  4. Douillard C, Jannin A, Vantyghem MC. Rare causes of hypoglycemia in adults. Ann Endocrinol (Paris). 2020;81(2-3):110-117. doi:10.1016/j.ando.2020.04.003

  5. Ekhlaspour L, Mondesir D, Lautsch N, et al. Comparative accuracy of 17 point-of-care glucose meters. J Diabetes Sci Technol. 2017;11(3):558-566. doi:10.1177/1932296816672237

  6. Alitta Q, Grino M, Adjemout L, Langar A, Retornaz F, Oliver C. Overestimation of hypoglycemia diagnosis by FreeStyle Libre continuous glucose monitoring in long-term care home residents with diabetes. J Diabetes Sci Technol. 2018;12(3):727-728. doi:10.1177/1932296817747887

  7. Mongraw-Chaffin M, Beavers DP, McClain DA. Hypoglycemic symptoms in the absence of diabetes: pilot evidence of clinical hypoglycemia in young women. J Clin Transl Endocrinol. 2019;18:100202. doi:10.1016/j.jcte.2019.100202 

  8. Shah VN, DuBose SN, Li Z, et al. Continuous glucose monitoring profiles in healthy nondiabetic participants: a multicenter prospective study. J Clin Endocrinol Metab. 2019;104(10):4356-4364. doi:10.1210/jc.2018-02763

  9. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2009;94(3):709-728. doi:10.1210/jc.2008-1410

  10. Galati SJ, Rayfield EJ. Approach to the patient with postprandial hypoglycemia. Endocr Pract. 2014;20(4):331-340. doi:10.4158/EP13132.RA

  11. Altuntas Y. Postprandial reactive hypoglycemia. Sisli Etfal Hastan Tip Bul. 2019;53(3):215-220.doi:10.14744/SEMB.2019.59455

  12. HARRIS S. HYPERINSULINISM AND DYSINSULINISM. JAMA. 1924;83(10):729-733.doi:10.1001/jama.1924.02660100003002

  13. Harris S. HYPERINSULINISM AND DYSINSULINISM (INSULOGENIC HYPOGLYCBMIA). Endocrinology. 1932;16(1):29-42. doi:10.1210/endo-16-1-29

  14. Hall M, Walicka M, Panczyk M, Traczyk I. Metabolic parameters in patients with suspected reactive hypoglycemia. J Pers Med. 2021;11(4):276. doi:10.3390/jpm11040276

  15. Kosuda M, Watanabe K, Koike M, et al. Glucagon response to glucose challenge in patients with idiopathic postprandial syndrome. J Nippon Med Sch. 2022;89(1):102-107. doi:10.1272/jnms.JNMS.2022_89-205

  16. Hall M, Walicka M, Panczyk M, Traczyk I. Assessing long-term impact of dietary interventions on occurrence of symptoms consistent with hypoglycemia in patients without diabetes: a one-year follow-up study. Nutrients. 2022;14(3):497. doi:10.3390/nu14030497

  17. Ozgen AG, Hamulu F, Bayraktar F, et al. Long-term treatment with acarbose for the treatment of reactive hypoglycemia. Eat Weight Disord. 1998;3(3):136-140. doi:10.1007/BF03340001

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Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. 

Ethics and consent

The patient described in this case report gave verbal and written informed consent.

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Author affiliations

aUniversity of California Los Angeles Geffen School of MedicinebWest Los Angeles Veterans Affairs Medical Center, California

Author disclosures

The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. 

Ethics and consent

The patient described in this case report gave verbal and written informed consent.

Idiopathic postprandial syndrome (IPP), initially termed reactive hypoglycemia, presents with hypoglycemic-like symptoms in the absence of biochemical hypoglycemia and remains a diagnosis of exclusion. Its pathophysiology is poorly understood. The diagnosis requires thorough evaluation of cardiac, metabolic, neurologic, and gastrointestinal causes, as well as Whipple triad criteria. Dietary modifications, including reduced carbohydrate intake, increased protein and fiber, and frequent small meals, remain the cornerstone of IPP management. Continuous glucose monitoring (CGM) may be a useful adjunct in correlating symptoms with glucose trends, but its role is still evolving.

In the evaluation of patients with symptoms suggestive of hypoglycemia (Figure 1), patients should first be assessed for Whipple triad: symptoms consistent with hypoglycemia, blood glucose level < 55 mg/dL, and reversal of symptoms with glucose.1 Patients who meet Whipple triad criteria should be investigated to identify further etiologies of hypoglycemia. They may include insulinoma, medication-induced (insulin, sulfonylurea, meglitinide, or β blocker use), postbariatric surgery complications, noninsulinoma pancreatogenous hypoglycemia syndrome, ackee fruit consumption, or familial conditions.2 The presence of hypoglycemic symptoms in the postprandial or fasting state can provide valuable insights into underlying etiology. 

Patients who do not meet Whipple triad criteria, but exhibit postprandial symptoms consistent with hypoglycemia, as in this case, present a diagnostic dilemma. IPP is defined as hypoglycemic symptoms occuring after carbohydrate ingestion without biochemical hypoglycemia. Initially termed reactive hypoglycemia, it was renamed in 1981to reflect the absence of low blood glucose levels.3

The understanding of this diagnosis has not significantly progressed since the 1980s. Its prevalence, incidence, risk factors, and societal burden remain unclear. IPP is a challenging diagnosis due to nonspecific symptoms that overlap with a myriad of conditions. These symptoms may include adrenergic symptoms such as diaphoresis, tremulousness, palpitations, anxiety, and hunger. Potentially severe neuroglycopenic symptoms, including weakness, dizziness, behavior changes, confusion, and coma, are not typically observed.4 Given that objective criteria are not well established, IPP remains a diagnosis of exclusion. It is imperative to rule out alternative etiologies, particularly cardiac, gastrointestinal, and neurologic causes.

CASE PRESENTATION

A male aged 41 years presented to primary care for evaluation of acute on chronic symptomatic postprandial episodes. He reported a history of symptomatic sinus bradycardia in the setting of sick sinus syndrome following dual-chamber pacemaker placement, posttraumatic stress disorder, and gastroesophageal reflux disease. He was a retired Navy sailor without any known occupational exposures who worked in the real estate industry. The patient reported feeling lightheaded, tremulous, and anxious most afternoons after lunch for several years. He also reported that meals heavy in carbohydrates exacerbated his symptoms, whereas skipping meals or lying down alleviated his symptoms. The patient also reported concomitant arm numbness, shortness of breath, palpitations, and nausea during these episodes. Review of systems was otherwise negative, including no weight changes, fever, chills, night sweats, chest pain, or syncope.

The patient’s medications included ferrous sulfate 325 mg once every other day, bupropion 200 mg once daily, metoprolol succinate 25 mg once daily, and as-needed lorazepam 1 mg once daily. The patient reported no current substance use but reported previous tobacco use 3 years prior (maximum 1 pack/week) and alcohol use 5 years prior (750 ml/day for 15 years). The patient did not exercise and typically ate oatmeal for breakfast, a sandwich or salad for lunch, and taquitos or salad for dinner, with snacks throughout the day. Notable family history included a maternal grandmother with colon cancer. The patient’s vital signs included a 36.8 °C temperature, heart rate 87 beats/min, 118/71 mm Hg blood pressure, oxygen saturation 98% on room air, 125.2 kg weight, and 38.5 body mass index. There were no orthostatic vital sign changes. A physical examination demonstrated obesity with an unremarkable cardiopulmonary and volume examination. 

Additional testing included Gallium-68 dototate positron emission tomography/computed tomography, brain magnetic resonance imaging, echocardiogram, electromyogram, exercise tolerance test, Holter monitoring, invasive cardiopulmonary exercise testing, pacemaker interrogation, pulmonary function testing, stress echocardiogram, tilt table test, and venogram computed tomography of the chest, but the results were unremarkable (Appendix). His afternoon nonfasting glucose level was 138 mg/dL with a concurrent hemoglobin A1c of 5.2%. The patient had a fasting C-peptide level of 3.7 ng/mL (reference range 0.5-2.0 ng/mL), fasting insulin level 19.1 mIU/L (reference range < 25 mIU/L), and a fasting glucose level of 93 mg/dL (reference range 70-99 mg/dL). The patient’s urine 5-HIAA, plasma metanephrines, urine metanephrines, insulin-like growth factor 1, prolactin, corticotropin, fasting cortisol, and thyrotropin yielded results within reference ranges (Table). The veteran was prescribed a CGM, which demonstrated normal glucose levels (≥ 55 mg/dL) during symptomatic episodes (Figure 2).



The patient was diagnosed with IPP given normoglycemia, exclusion of alternative diagnoses, and symptomatic improvement with dietary changes. He was referred to a nutritionist for a high-protein, high-fiber, and low-carbohydrate diet.

DISCUSSION

Seemingly simple diagnostic tools can lead to diagnostic pitfalls. Home glucose monitoring with the use of a standard glucometer during an episode is the typical first step in identifying hypoglycemia, as it is both pragmatic and accurate, with a mean absolute relative difference (MARD) of about 10% in hypoglycemic ranges.5 While the advent of CGM provides real-time data and can reveal clinically relevant fluctuations, it reveals mild hypoglycemia (54 to 70 mg/dL) of no clinical significance in a large proportion of individuals.

Additionally, CGM is less accurate than glucometers with a MARD of about 20% in hypoglycemia ranges.6 CGM technology, however, is rapidly evolving and undergoing further investigation for hypoglycemia detection. Therefore, CGM may be considered in select patients as prospective study results are established; the newest CGMs have MARDs very similar to fingerstick blood glucose data.7,8 In the patient described in this case, CGM helped corroborate the diagnosis, given that symptomatic episodes correlated with lower glucose levels. Provocative testing with oral glucose tolerance testing can frequently result in false positive hypoglycemic readings and is not recommended.9 Supervised mixed meal testing can also be used, which entails monitoring after consuming a mixed macronutrient meal. The test concludes after hypoglycemic symptoms develop or 5 hours elapse, whichever occurs first.1

 

The pathophysiology of IPP is poorly understood. Proposed mechanisms include increased insulin sensitivity, increased adrenergic sensitivity, impaired glucagon regulation, emotional distress, insulin resistance, and increased glucagon-like peptide-1 production.10-13 Research suggests this may occur as pancreatic β cells fail in early type 2 diabetes mellitus, with diminished first-phase insulin release leading to an initial exuberant rise in blood glucose, an overshooting of the second phase of insulin secretion, and the feeling of the postprandial blood glucose falling, even though the final glucose level achieved is not truly low.13 There are contradictory studies in the literature demonstrating no association between insulin resistance and hypoglycemic symptoms.14 In 2022, Kosuda and colleagues looked at homeostatic model assessment for insulin resistance in patients with postprandial syndrome. They found that the patients were slightly insulin resistant but had normal or exaggerated insulin secretory capacity compared to an oral glucose load, whereas glucagon levels were robustly suppressed by a glucose load. The observed hormonal responses may result in the glycemic patterns and symptoms observed; further study is warranted to elucidate the mechanism.15

Dietary modification is the cornerstone treatment for postprandial syndrome, including reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals. There is also evidence that a Mediterranean diet may be beneficial for managing hypoglycemic symptoms.16 Furthermore, α-glucosidase inhibitors, whose mechanism of action delays the digestion of carbohydrates, have demonstrated promise. This medication class has demonstrated significance in raising postprandial glucose levels and alleviating hypoglycemic symptoms in patients with true postprandial hypoglycemia.17

CONCLUSIONS

IPP is a benign diagnosis encompassing hypoglycemic symptoms without biochemical hypoglycemia. It is not a true hypoglycemic disorder. IPP is challenging to diagnose, given that it is an interpretation of exclusion, supported by symptom improvement with dietary changes (ie, reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals). Supervised mixed meal testing or CGM can be used to assist with diagnosis. Even though CGM is undergoing further study in this patient population, it corroborated the diagnosis in the patient described in this case.

For hypoglycemic symptoms, physicians should first assess for evidence of Whipple triad to evaluate for true biochemical hypoglycemia. For true hypoglycemia (< 55 mg/dL), physicians may conduct an examination in conjunction with an endocrinologist. For normoglycemia (≥ 55 mg/dL), physicians should first exclude alternative etiologies (including cardiac and neurologic), and subsequently consider IPP.

Idiopathic postprandial syndrome (IPP), initially termed reactive hypoglycemia, presents with hypoglycemic-like symptoms in the absence of biochemical hypoglycemia and remains a diagnosis of exclusion. Its pathophysiology is poorly understood. The diagnosis requires thorough evaluation of cardiac, metabolic, neurologic, and gastrointestinal causes, as well as Whipple triad criteria. Dietary modifications, including reduced carbohydrate intake, increased protein and fiber, and frequent small meals, remain the cornerstone of IPP management. Continuous glucose monitoring (CGM) may be a useful adjunct in correlating symptoms with glucose trends, but its role is still evolving.

In the evaluation of patients with symptoms suggestive of hypoglycemia (Figure 1), patients should first be assessed for Whipple triad: symptoms consistent with hypoglycemia, blood glucose level < 55 mg/dL, and reversal of symptoms with glucose.1 Patients who meet Whipple triad criteria should be investigated to identify further etiologies of hypoglycemia. They may include insulinoma, medication-induced (insulin, sulfonylurea, meglitinide, or β blocker use), postbariatric surgery complications, noninsulinoma pancreatogenous hypoglycemia syndrome, ackee fruit consumption, or familial conditions.2 The presence of hypoglycemic symptoms in the postprandial or fasting state can provide valuable insights into underlying etiology. 

Patients who do not meet Whipple triad criteria, but exhibit postprandial symptoms consistent with hypoglycemia, as in this case, present a diagnostic dilemma. IPP is defined as hypoglycemic symptoms occuring after carbohydrate ingestion without biochemical hypoglycemia. Initially termed reactive hypoglycemia, it was renamed in 1981to reflect the absence of low blood glucose levels.3

The understanding of this diagnosis has not significantly progressed since the 1980s. Its prevalence, incidence, risk factors, and societal burden remain unclear. IPP is a challenging diagnosis due to nonspecific symptoms that overlap with a myriad of conditions. These symptoms may include adrenergic symptoms such as diaphoresis, tremulousness, palpitations, anxiety, and hunger. Potentially severe neuroglycopenic symptoms, including weakness, dizziness, behavior changes, confusion, and coma, are not typically observed.4 Given that objective criteria are not well established, IPP remains a diagnosis of exclusion. It is imperative to rule out alternative etiologies, particularly cardiac, gastrointestinal, and neurologic causes.

CASE PRESENTATION

A male aged 41 years presented to primary care for evaluation of acute on chronic symptomatic postprandial episodes. He reported a history of symptomatic sinus bradycardia in the setting of sick sinus syndrome following dual-chamber pacemaker placement, posttraumatic stress disorder, and gastroesophageal reflux disease. He was a retired Navy sailor without any known occupational exposures who worked in the real estate industry. The patient reported feeling lightheaded, tremulous, and anxious most afternoons after lunch for several years. He also reported that meals heavy in carbohydrates exacerbated his symptoms, whereas skipping meals or lying down alleviated his symptoms. The patient also reported concomitant arm numbness, shortness of breath, palpitations, and nausea during these episodes. Review of systems was otherwise negative, including no weight changes, fever, chills, night sweats, chest pain, or syncope.

The patient’s medications included ferrous sulfate 325 mg once every other day, bupropion 200 mg once daily, metoprolol succinate 25 mg once daily, and as-needed lorazepam 1 mg once daily. The patient reported no current substance use but reported previous tobacco use 3 years prior (maximum 1 pack/week) and alcohol use 5 years prior (750 ml/day for 15 years). The patient did not exercise and typically ate oatmeal for breakfast, a sandwich or salad for lunch, and taquitos or salad for dinner, with snacks throughout the day. Notable family history included a maternal grandmother with colon cancer. The patient’s vital signs included a 36.8 °C temperature, heart rate 87 beats/min, 118/71 mm Hg blood pressure, oxygen saturation 98% on room air, 125.2 kg weight, and 38.5 body mass index. There were no orthostatic vital sign changes. A physical examination demonstrated obesity with an unremarkable cardiopulmonary and volume examination. 

Additional testing included Gallium-68 dototate positron emission tomography/computed tomography, brain magnetic resonance imaging, echocardiogram, electromyogram, exercise tolerance test, Holter monitoring, invasive cardiopulmonary exercise testing, pacemaker interrogation, pulmonary function testing, stress echocardiogram, tilt table test, and venogram computed tomography of the chest, but the results were unremarkable (Appendix). His afternoon nonfasting glucose level was 138 mg/dL with a concurrent hemoglobin A1c of 5.2%. The patient had a fasting C-peptide level of 3.7 ng/mL (reference range 0.5-2.0 ng/mL), fasting insulin level 19.1 mIU/L (reference range < 25 mIU/L), and a fasting glucose level of 93 mg/dL (reference range 70-99 mg/dL). The patient’s urine 5-HIAA, plasma metanephrines, urine metanephrines, insulin-like growth factor 1, prolactin, corticotropin, fasting cortisol, and thyrotropin yielded results within reference ranges (Table). The veteran was prescribed a CGM, which demonstrated normal glucose levels (≥ 55 mg/dL) during symptomatic episodes (Figure 2).



The patient was diagnosed with IPP given normoglycemia, exclusion of alternative diagnoses, and symptomatic improvement with dietary changes. He was referred to a nutritionist for a high-protein, high-fiber, and low-carbohydrate diet.

DISCUSSION

Seemingly simple diagnostic tools can lead to diagnostic pitfalls. Home glucose monitoring with the use of a standard glucometer during an episode is the typical first step in identifying hypoglycemia, as it is both pragmatic and accurate, with a mean absolute relative difference (MARD) of about 10% in hypoglycemic ranges.5 While the advent of CGM provides real-time data and can reveal clinically relevant fluctuations, it reveals mild hypoglycemia (54 to 70 mg/dL) of no clinical significance in a large proportion of individuals.

Additionally, CGM is less accurate than glucometers with a MARD of about 20% in hypoglycemia ranges.6 CGM technology, however, is rapidly evolving and undergoing further investigation for hypoglycemia detection. Therefore, CGM may be considered in select patients as prospective study results are established; the newest CGMs have MARDs very similar to fingerstick blood glucose data.7,8 In the patient described in this case, CGM helped corroborate the diagnosis, given that symptomatic episodes correlated with lower glucose levels. Provocative testing with oral glucose tolerance testing can frequently result in false positive hypoglycemic readings and is not recommended.9 Supervised mixed meal testing can also be used, which entails monitoring after consuming a mixed macronutrient meal. The test concludes after hypoglycemic symptoms develop or 5 hours elapse, whichever occurs first.1

 

The pathophysiology of IPP is poorly understood. Proposed mechanisms include increased insulin sensitivity, increased adrenergic sensitivity, impaired glucagon regulation, emotional distress, insulin resistance, and increased glucagon-like peptide-1 production.10-13 Research suggests this may occur as pancreatic β cells fail in early type 2 diabetes mellitus, with diminished first-phase insulin release leading to an initial exuberant rise in blood glucose, an overshooting of the second phase of insulin secretion, and the feeling of the postprandial blood glucose falling, even though the final glucose level achieved is not truly low.13 There are contradictory studies in the literature demonstrating no association between insulin resistance and hypoglycemic symptoms.14 In 2022, Kosuda and colleagues looked at homeostatic model assessment for insulin resistance in patients with postprandial syndrome. They found that the patients were slightly insulin resistant but had normal or exaggerated insulin secretory capacity compared to an oral glucose load, whereas glucagon levels were robustly suppressed by a glucose load. The observed hormonal responses may result in the glycemic patterns and symptoms observed; further study is warranted to elucidate the mechanism.15

Dietary modification is the cornerstone treatment for postprandial syndrome, including reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals. There is also evidence that a Mediterranean diet may be beneficial for managing hypoglycemic symptoms.16 Furthermore, α-glucosidase inhibitors, whose mechanism of action delays the digestion of carbohydrates, have demonstrated promise. This medication class has demonstrated significance in raising postprandial glucose levels and alleviating hypoglycemic symptoms in patients with true postprandial hypoglycemia.17

CONCLUSIONS

IPP is a benign diagnosis encompassing hypoglycemic symptoms without biochemical hypoglycemia. It is not a true hypoglycemic disorder. IPP is challenging to diagnose, given that it is an interpretation of exclusion, supported by symptom improvement with dietary changes (ie, reduced carbohydrate intake, increased protein and fiber intake, and more frequent and smaller meals). Supervised mixed meal testing or CGM can be used to assist with diagnosis. Even though CGM is undergoing further study in this patient population, it corroborated the diagnosis in the patient described in this case.

For hypoglycemic symptoms, physicians should first assess for evidence of Whipple triad to evaluate for true biochemical hypoglycemia. For true hypoglycemia (< 55 mg/dL), physicians may conduct an examination in conjunction with an endocrinologist. For normoglycemia (≥ 55 mg/dL), physicians should first exclude alternative etiologies (including cardiac and neurologic), and subsequently consider IPP.

References
  1. Bansal N, Weinstock RS. Non-Diabetic Hypoglycemia. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext. MDText.com, Inc.; 2000.

  2. Service FJ. Hypoglycemic disorders. New Engl J Med. 1995;332(17):1144-1152.doi:10.1056/NEJM199504273321707

  3. Charles MA, Hofeldt F, Shackelford A, et al. Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals. Diabetes. 1981;30(6):465-470.

  4. Douillard C, Jannin A, Vantyghem MC. Rare causes of hypoglycemia in adults. Ann Endocrinol (Paris). 2020;81(2-3):110-117. doi:10.1016/j.ando.2020.04.003

  5. Ekhlaspour L, Mondesir D, Lautsch N, et al. Comparative accuracy of 17 point-of-care glucose meters. J Diabetes Sci Technol. 2017;11(3):558-566. doi:10.1177/1932296816672237

  6. Alitta Q, Grino M, Adjemout L, Langar A, Retornaz F, Oliver C. Overestimation of hypoglycemia diagnosis by FreeStyle Libre continuous glucose monitoring in long-term care home residents with diabetes. J Diabetes Sci Technol. 2018;12(3):727-728. doi:10.1177/1932296817747887

  7. Mongraw-Chaffin M, Beavers DP, McClain DA. Hypoglycemic symptoms in the absence of diabetes: pilot evidence of clinical hypoglycemia in young women. J Clin Transl Endocrinol. 2019;18:100202. doi:10.1016/j.jcte.2019.100202 

  8. Shah VN, DuBose SN, Li Z, et al. Continuous glucose monitoring profiles in healthy nondiabetic participants: a multicenter prospective study. J Clin Endocrinol Metab. 2019;104(10):4356-4364. doi:10.1210/jc.2018-02763

  9. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2009;94(3):709-728. doi:10.1210/jc.2008-1410

  10. Galati SJ, Rayfield EJ. Approach to the patient with postprandial hypoglycemia. Endocr Pract. 2014;20(4):331-340. doi:10.4158/EP13132.RA

  11. Altuntas Y. Postprandial reactive hypoglycemia. Sisli Etfal Hastan Tip Bul. 2019;53(3):215-220.doi:10.14744/SEMB.2019.59455

  12. HARRIS S. HYPERINSULINISM AND DYSINSULINISM. JAMA. 1924;83(10):729-733.doi:10.1001/jama.1924.02660100003002

  13. Harris S. HYPERINSULINISM AND DYSINSULINISM (INSULOGENIC HYPOGLYCBMIA). Endocrinology. 1932;16(1):29-42. doi:10.1210/endo-16-1-29

  14. Hall M, Walicka M, Panczyk M, Traczyk I. Metabolic parameters in patients with suspected reactive hypoglycemia. J Pers Med. 2021;11(4):276. doi:10.3390/jpm11040276

  15. Kosuda M, Watanabe K, Koike M, et al. Glucagon response to glucose challenge in patients with idiopathic postprandial syndrome. J Nippon Med Sch. 2022;89(1):102-107. doi:10.1272/jnms.JNMS.2022_89-205

  16. Hall M, Walicka M, Panczyk M, Traczyk I. Assessing long-term impact of dietary interventions on occurrence of symptoms consistent with hypoglycemia in patients without diabetes: a one-year follow-up study. Nutrients. 2022;14(3):497. doi:10.3390/nu14030497

  17. Ozgen AG, Hamulu F, Bayraktar F, et al. Long-term treatment with acarbose for the treatment of reactive hypoglycemia. Eat Weight Disord. 1998;3(3):136-140. doi:10.1007/BF03340001

References
  1. Bansal N, Weinstock RS. Non-Diabetic Hypoglycemia. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext. MDText.com, Inc.; 2000.

  2. Service FJ. Hypoglycemic disorders. New Engl J Med. 1995;332(17):1144-1152.doi:10.1056/NEJM199504273321707

  3. Charles MA, Hofeldt F, Shackelford A, et al. Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals. Diabetes. 1981;30(6):465-470.

  4. Douillard C, Jannin A, Vantyghem MC. Rare causes of hypoglycemia in adults. Ann Endocrinol (Paris). 2020;81(2-3):110-117. doi:10.1016/j.ando.2020.04.003

  5. Ekhlaspour L, Mondesir D, Lautsch N, et al. Comparative accuracy of 17 point-of-care glucose meters. J Diabetes Sci Technol. 2017;11(3):558-566. doi:10.1177/1932296816672237

  6. Alitta Q, Grino M, Adjemout L, Langar A, Retornaz F, Oliver C. Overestimation of hypoglycemia diagnosis by FreeStyle Libre continuous glucose monitoring in long-term care home residents with diabetes. J Diabetes Sci Technol. 2018;12(3):727-728. doi:10.1177/1932296817747887

  7. Mongraw-Chaffin M, Beavers DP, McClain DA. Hypoglycemic symptoms in the absence of diabetes: pilot evidence of clinical hypoglycemia in young women. J Clin Transl Endocrinol. 2019;18:100202. doi:10.1016/j.jcte.2019.100202 

  8. Shah VN, DuBose SN, Li Z, et al. Continuous glucose monitoring profiles in healthy nondiabetic participants: a multicenter prospective study. J Clin Endocrinol Metab. 2019;104(10):4356-4364. doi:10.1210/jc.2018-02763

  9. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2009;94(3):709-728. doi:10.1210/jc.2008-1410

  10. Galati SJ, Rayfield EJ. Approach to the patient with postprandial hypoglycemia. Endocr Pract. 2014;20(4):331-340. doi:10.4158/EP13132.RA

  11. Altuntas Y. Postprandial reactive hypoglycemia. Sisli Etfal Hastan Tip Bul. 2019;53(3):215-220.doi:10.14744/SEMB.2019.59455

  12. HARRIS S. HYPERINSULINISM AND DYSINSULINISM. JAMA. 1924;83(10):729-733.doi:10.1001/jama.1924.02660100003002

  13. Harris S. HYPERINSULINISM AND DYSINSULINISM (INSULOGENIC HYPOGLYCBMIA). Endocrinology. 1932;16(1):29-42. doi:10.1210/endo-16-1-29

  14. Hall M, Walicka M, Panczyk M, Traczyk I. Metabolic parameters in patients with suspected reactive hypoglycemia. J Pers Med. 2021;11(4):276. doi:10.3390/jpm11040276

  15. Kosuda M, Watanabe K, Koike M, et al. Glucagon response to glucose challenge in patients with idiopathic postprandial syndrome. J Nippon Med Sch. 2022;89(1):102-107. doi:10.1272/jnms.JNMS.2022_89-205

  16. Hall M, Walicka M, Panczyk M, Traczyk I. Assessing long-term impact of dietary interventions on occurrence of symptoms consistent with hypoglycemia in patients without diabetes: a one-year follow-up study. Nutrients. 2022;14(3):497. doi:10.3390/nu14030497

  17. Ozgen AG, Hamulu F, Bayraktar F, et al. Long-term treatment with acarbose for the treatment of reactive hypoglycemia. Eat Weight Disord. 1998;3(3):136-140. doi:10.1007/BF03340001

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Key Features of Dermatosis Papulosa Nigra vs Seborrheic Keratosis

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Key Features of Dermatosis Papulosa Nigra vs Seborrheic Keratosis

DX ACROSS THE SKIN COLOR SPECTRUM

Dermatosis papulosa nigra (DPN), a subvariant of seborrheic keratosis (SK), is characterized by benign pigmented epidermal neoplasms that typically manifest on the face, neck, and trunk in individuals with darker skin tones (Figure).1,2 While DPN meets the diagnostic criteria for SK, certain characteristics can help distinguish these lesions from other SK types. Treatment of DPN in patients with skin of color requires caution, particularly regarding the use of abrasive methods as well as cryotherapy, which generally should be avoided. 

EPIDEMIOLOGY 

The incidence of SKs increases with age.3,4 Although it can occur in patients of all skin tones, SK is more common in lighter skin tones, while DPN predominantly is diagnosed in darker skin types.1,4 The prevalence of DPN in Black patients ranges from 10% to 30%, and Black women are twice as likely to be diagnosed with DPN as men.2 One study reported a first-degree relative with DPN in 84% (42/50) of patients.5 The number and size of DPN papules increase with age.1 

KEY CLINICAL FEATURES 

Dermatosis papulosa nigra and SK have distinctive morphologies: DPN typically manifests as raised, round or filiform, sessile, brown to black, 1- to 5-mm papules. 2 Seborrheic keratoses tend to be larger with a “stuck on” appearance and manifest as well-demarcated, pink to black papules or plaques that can range in size from millimeters to a few centimeters. 3,4 In DPN, the lesions usually are asymptomatic but may be tender, pruritic, dry, or scaly and may become irritated.1,2 They develop symmetrically in sun-exposed areas, and the most common sites are the malar face, temporal region, neck, and trunk.1,2,6,7 Seborrheic keratoses can appear throughout the body, including in sun-exposed areas, but have varying textures (eg, greasy, waxy, verrucous).3,4 

WORTH NOTING 

Dermatosis papulosa nigra and SK can resemble each other histologically: DPN demonstrates a fibrous stroma, papillomatosis, hyperkeratosis, and acanthosis at the intraepidermal layer, which are diagnostic criteria for SK.2,4,8 However, other histologic features characteristic of SK that are not seen in DPN include pseudohorn cysts, spindle tumor cells, and basaloid cell nests.8 

Dermoscopy can be useful in ruling out malignant skin cancers when evaluating pigmented lesions. The most common dermoscopic features of SK are cerebriform patterns such as fissures and ridges, comedolike openings, and pigmented fingerprintlike structures.3,4 To a lesser degree, milialike cysts, sharp demarcation, and hairpin-shaped vascular structures also may be present.4 The dermoscopic findings of DPN have not been well evaluated, but one study revealed that DPN had similar dermoscopic features to SK with some predominant features.6 Ridges and fissures were seen in 59% of patients diagnosed with DPN followed by comedolike openings seen in 27% of patients. The coexistence of a cerebriform pattern with comedolike openings was infrequent, and milialike cysts were rare.6 

While DPN and SK are benign, patients often seek treatment for cosmetic reasons. Factors to consider when choosing a treatment modality include location of the lesions, the patient’s skin tone, and postprocedural outcomes (eg, depigmentation, wound healing). In general, treatments for SK include cryotherapy, electrodesiccation and curettage, and topical therapeutics such as hydrogen peroxide 40%, topical vitamin D3, and nitric-zinc 30%-50% solutions. 4,8 Well-established treatment options for DPN include electrodesiccation, laser therapies, scissor excision, and cryotherapy, but topical options such as tazarotene also have been reported.1,9 Of the treatments for DPN, electrodesiccation and laser therapy routinely are used.10 

The efficacy of electrodessication and potassium titanyl phosphate (KTP) laser were assessed in a randomized, investigatorblinded split-face study.11 Both modalities received high improvement ratings, with the results favoring the KTP laser. The patients (most of whom were Black) reported that KTP laser was more effective but more painful than electrodessication (P =.002).11 In another randomized study, patients received 3 treatments—electrodessication, pulsed dye laser, and curettage—for select DPN papules.10 There was no difference in the degree of clearance, cosmetic outcome, or postinflammatory hyperpigmentation between the 3 modalities, but patients found the laser to be the most painful. 

It is important to exercise caution when using abrasive methods (eg, laser therapy, electrodesiccation, curettage) in patients with darker skin tones because of the increased risk for postinflammatory pigment alteration.1,2,12 Adverse effects of treatment are a top concern in the management of DPN.5,13 While cryotherapy is a preferred treatment of SK in lighter skin tones, it generally is avoided for DPN in darker skin types because melanocyte destruction can lead to cosmetically unsatisfactory and easily visible depigmentation.9 

To mitigate postprocedural adverse effects, proper aftercare can promote wound healing and minimize postinflammatory pigment alteration. In one split-face study of Black patients, 2 DPN papules were removed from each side of the face using fine-curved surgical scissors.14 Next, a petrolatum-based ointment and an antibiotic ointment with polymyxin B sulfate/bacitracin zinc was applied twice daily for 21 days to opposite sides of the face. Patients did not develop infection, tolerated both treatments well, and demonstrated improved general wound appearance according to investigator- rated clinical assessment.14 Other reported postprocedural approaches include using topical agents with ingredients shown to improve hyperpigmentation (eg, niacinamide, azelaic acid) as well as photoprotection.12 

HEALTH DISPARITY HIGHLIGHT 

While DPN is benign, it can have adverse psychosocial effects on patients. A study in Senegal revealed that 60% (19/30) of patients with DPN experienced anxiety related to their condition, while others noted that DPN hindered their social relationships.13 In one US study of 50 Black patients with DPN, there was a moderate effect on quality of life, and 36% (18/50) of patients had the lesions removed. However, of the treated patients, 67% (12/18) reported few—if any—symptoms prior to removal.5 Although treatment of DPN is widely considered a cosmetic procedure, therapeutic management can address— and may improve—mental health in patients with skin of color.1,5,13 Despite the high prevalence of DPN in patients with darker skin tones, data on treatment frequency and insurance coverage are not widely available, thus limiting our understanding of treatment accessibility and economic burden. 

References
  1. Frazier WT, Proddutur S, Swope K. Common dermatologic conditions in skin of color. Am Fam Physician. 2023;107:26-34. 
  2. Metin SA, Lee BW, Lambert WC, et al. Dermatosis papulosa nigra: a clinically and histopathologically distinct entity. Clin Dermatol. 2017;35:491-496. 
  3. Braun RP, Ludwig S, Marghoob AA. Differential diagnosis of seborrheic keratosis: clinical and dermoscopic features. J Drugs Dermatol. 2017;16:835-842. 
  4. Sun MD, Halpern AC. Advances in the etiology, detection, and clinical management of seborrheic keratoses. Dermatology. 2022;238:205-217. 
  5. Uwakwe LN, De Souza B, Subash J, et al. Dermatosis papulosa nigra: a quality of life survey study. J Clin Aesthet Dermatol. 2020;13:17-19. 
  6. Bhat RM, Patrao N, Monteiro R, et al. A clinical, dermoscopic, and histopathological study of dermatosis papulosa nigra (DPN)—an Indian perspective. Int J Dermatol. 2017;56:957-960. 
  7. Karampinis E, Georgopoulou KE, Kampra E, et al. Clinical and dermoscopic patterns of basal cell carcinoma and its mimickers in skin of color: a practical summary. Medicina (Kaunas). 2024;60:1386. 
  8. Gorai S, Ahmad S, Raza SSM, et al. Update of pathophysiology and treatment options of seborrheic keratosis. Dermatol Ther. 2022;35:E15934. 
  9. Jain S, Caire H, Haas CJ. Management of dermatosis papulosa nigra: a systematic review. Int J Dermatol. Published online October 4, 2024. 
  10. Garcia MS, Azari R, Eisen DB. Treatment of dermatosis papulosa nigra in 10 patients: a comparison trial of electrodesiccation, pulsed dye laser, and curettage. Dermatol Surg. 2010;36:1968-1972. 
  11. Kundu RV, Joshi SS, Suh KY, et al. Comparison of electrodesiccation and potassium-titanyl-phosphate laser for treatment of dermatosis papulosa nigra. Dermatol Surg. 2009;35:1079-1083. 
  12. Markiewicz E, Karaman-Jurukovska N, Mammone T, et al. Post-inflammatory hyperpigmentation in dark skin: molecular mechanism and skincare implications. Clin Cosmet Investig Dermatol. 2022;15:2555-2565. 
  13. Niang SO, Kane A, Diallo M, et al. Dermatosis papulosa nigra in Dakar, Senegal. Int J Dermatol. 2007;46(suppl 1):45-47. 
  14. Taylor SC, Averyhart AN, Heath CR. Postprocedural wound-healing efficacy following removal of dermatosis papulosa nigra lesions in an African American population: a comparison of a skin protectant ointment and a topical antibiotic. J Am Acad Dermatol. 2011;64(suppl 3):S30-S35.
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DX ACROSS THE SKIN COLOR SPECTRUM
DX ACROSS THE SKIN COLOR SPECTRUM

Dermatosis papulosa nigra (DPN), a subvariant of seborrheic keratosis (SK), is characterized by benign pigmented epidermal neoplasms that typically manifest on the face, neck, and trunk in individuals with darker skin tones (Figure).1,2 While DPN meets the diagnostic criteria for SK, certain characteristics can help distinguish these lesions from other SK types. Treatment of DPN in patients with skin of color requires caution, particularly regarding the use of abrasive methods as well as cryotherapy, which generally should be avoided. 

EPIDEMIOLOGY 

The incidence of SKs increases with age.3,4 Although it can occur in patients of all skin tones, SK is more common in lighter skin tones, while DPN predominantly is diagnosed in darker skin types.1,4 The prevalence of DPN in Black patients ranges from 10% to 30%, and Black women are twice as likely to be diagnosed with DPN as men.2 One study reported a first-degree relative with DPN in 84% (42/50) of patients.5 The number and size of DPN papules increase with age.1 

KEY CLINICAL FEATURES 

Dermatosis papulosa nigra and SK have distinctive morphologies: DPN typically manifests as raised, round or filiform, sessile, brown to black, 1- to 5-mm papules. 2 Seborrheic keratoses tend to be larger with a “stuck on” appearance and manifest as well-demarcated, pink to black papules or plaques that can range in size from millimeters to a few centimeters. 3,4 In DPN, the lesions usually are asymptomatic but may be tender, pruritic, dry, or scaly and may become irritated.1,2 They develop symmetrically in sun-exposed areas, and the most common sites are the malar face, temporal region, neck, and trunk.1,2,6,7 Seborrheic keratoses can appear throughout the body, including in sun-exposed areas, but have varying textures (eg, greasy, waxy, verrucous).3,4 

WORTH NOTING 

Dermatosis papulosa nigra and SK can resemble each other histologically: DPN demonstrates a fibrous stroma, papillomatosis, hyperkeratosis, and acanthosis at the intraepidermal layer, which are diagnostic criteria for SK.2,4,8 However, other histologic features characteristic of SK that are not seen in DPN include pseudohorn cysts, spindle tumor cells, and basaloid cell nests.8 

Dermoscopy can be useful in ruling out malignant skin cancers when evaluating pigmented lesions. The most common dermoscopic features of SK are cerebriform patterns such as fissures and ridges, comedolike openings, and pigmented fingerprintlike structures.3,4 To a lesser degree, milialike cysts, sharp demarcation, and hairpin-shaped vascular structures also may be present.4 The dermoscopic findings of DPN have not been well evaluated, but one study revealed that DPN had similar dermoscopic features to SK with some predominant features.6 Ridges and fissures were seen in 59% of patients diagnosed with DPN followed by comedolike openings seen in 27% of patients. The coexistence of a cerebriform pattern with comedolike openings was infrequent, and milialike cysts were rare.6 

While DPN and SK are benign, patients often seek treatment for cosmetic reasons. Factors to consider when choosing a treatment modality include location of the lesions, the patient’s skin tone, and postprocedural outcomes (eg, depigmentation, wound healing). In general, treatments for SK include cryotherapy, electrodesiccation and curettage, and topical therapeutics such as hydrogen peroxide 40%, topical vitamin D3, and nitric-zinc 30%-50% solutions. 4,8 Well-established treatment options for DPN include electrodesiccation, laser therapies, scissor excision, and cryotherapy, but topical options such as tazarotene also have been reported.1,9 Of the treatments for DPN, electrodesiccation and laser therapy routinely are used.10 

The efficacy of electrodessication and potassium titanyl phosphate (KTP) laser were assessed in a randomized, investigatorblinded split-face study.11 Both modalities received high improvement ratings, with the results favoring the KTP laser. The patients (most of whom were Black) reported that KTP laser was more effective but more painful than electrodessication (P =.002).11 In another randomized study, patients received 3 treatments—electrodessication, pulsed dye laser, and curettage—for select DPN papules.10 There was no difference in the degree of clearance, cosmetic outcome, or postinflammatory hyperpigmentation between the 3 modalities, but patients found the laser to be the most painful. 

It is important to exercise caution when using abrasive methods (eg, laser therapy, electrodesiccation, curettage) in patients with darker skin tones because of the increased risk for postinflammatory pigment alteration.1,2,12 Adverse effects of treatment are a top concern in the management of DPN.5,13 While cryotherapy is a preferred treatment of SK in lighter skin tones, it generally is avoided for DPN in darker skin types because melanocyte destruction can lead to cosmetically unsatisfactory and easily visible depigmentation.9 

To mitigate postprocedural adverse effects, proper aftercare can promote wound healing and minimize postinflammatory pigment alteration. In one split-face study of Black patients, 2 DPN papules were removed from each side of the face using fine-curved surgical scissors.14 Next, a petrolatum-based ointment and an antibiotic ointment with polymyxin B sulfate/bacitracin zinc was applied twice daily for 21 days to opposite sides of the face. Patients did not develop infection, tolerated both treatments well, and demonstrated improved general wound appearance according to investigator- rated clinical assessment.14 Other reported postprocedural approaches include using topical agents with ingredients shown to improve hyperpigmentation (eg, niacinamide, azelaic acid) as well as photoprotection.12 

HEALTH DISPARITY HIGHLIGHT 

While DPN is benign, it can have adverse psychosocial effects on patients. A study in Senegal revealed that 60% (19/30) of patients with DPN experienced anxiety related to their condition, while others noted that DPN hindered their social relationships.13 In one US study of 50 Black patients with DPN, there was a moderate effect on quality of life, and 36% (18/50) of patients had the lesions removed. However, of the treated patients, 67% (12/18) reported few—if any—symptoms prior to removal.5 Although treatment of DPN is widely considered a cosmetic procedure, therapeutic management can address— and may improve—mental health in patients with skin of color.1,5,13 Despite the high prevalence of DPN in patients with darker skin tones, data on treatment frequency and insurance coverage are not widely available, thus limiting our understanding of treatment accessibility and economic burden. 

Dermatosis papulosa nigra (DPN), a subvariant of seborrheic keratosis (SK), is characterized by benign pigmented epidermal neoplasms that typically manifest on the face, neck, and trunk in individuals with darker skin tones (Figure).1,2 While DPN meets the diagnostic criteria for SK, certain characteristics can help distinguish these lesions from other SK types. Treatment of DPN in patients with skin of color requires caution, particularly regarding the use of abrasive methods as well as cryotherapy, which generally should be avoided. 

EPIDEMIOLOGY 

The incidence of SKs increases with age.3,4 Although it can occur in patients of all skin tones, SK is more common in lighter skin tones, while DPN predominantly is diagnosed in darker skin types.1,4 The prevalence of DPN in Black patients ranges from 10% to 30%, and Black women are twice as likely to be diagnosed with DPN as men.2 One study reported a first-degree relative with DPN in 84% (42/50) of patients.5 The number and size of DPN papules increase with age.1 

KEY CLINICAL FEATURES 

Dermatosis papulosa nigra and SK have distinctive morphologies: DPN typically manifests as raised, round or filiform, sessile, brown to black, 1- to 5-mm papules. 2 Seborrheic keratoses tend to be larger with a “stuck on” appearance and manifest as well-demarcated, pink to black papules or plaques that can range in size from millimeters to a few centimeters. 3,4 In DPN, the lesions usually are asymptomatic but may be tender, pruritic, dry, or scaly and may become irritated.1,2 They develop symmetrically in sun-exposed areas, and the most common sites are the malar face, temporal region, neck, and trunk.1,2,6,7 Seborrheic keratoses can appear throughout the body, including in sun-exposed areas, but have varying textures (eg, greasy, waxy, verrucous).3,4 

WORTH NOTING 

Dermatosis papulosa nigra and SK can resemble each other histologically: DPN demonstrates a fibrous stroma, papillomatosis, hyperkeratosis, and acanthosis at the intraepidermal layer, which are diagnostic criteria for SK.2,4,8 However, other histologic features characteristic of SK that are not seen in DPN include pseudohorn cysts, spindle tumor cells, and basaloid cell nests.8 

Dermoscopy can be useful in ruling out malignant skin cancers when evaluating pigmented lesions. The most common dermoscopic features of SK are cerebriform patterns such as fissures and ridges, comedolike openings, and pigmented fingerprintlike structures.3,4 To a lesser degree, milialike cysts, sharp demarcation, and hairpin-shaped vascular structures also may be present.4 The dermoscopic findings of DPN have not been well evaluated, but one study revealed that DPN had similar dermoscopic features to SK with some predominant features.6 Ridges and fissures were seen in 59% of patients diagnosed with DPN followed by comedolike openings seen in 27% of patients. The coexistence of a cerebriform pattern with comedolike openings was infrequent, and milialike cysts were rare.6 

While DPN and SK are benign, patients often seek treatment for cosmetic reasons. Factors to consider when choosing a treatment modality include location of the lesions, the patient’s skin tone, and postprocedural outcomes (eg, depigmentation, wound healing). In general, treatments for SK include cryotherapy, electrodesiccation and curettage, and topical therapeutics such as hydrogen peroxide 40%, topical vitamin D3, and nitric-zinc 30%-50% solutions. 4,8 Well-established treatment options for DPN include electrodesiccation, laser therapies, scissor excision, and cryotherapy, but topical options such as tazarotene also have been reported.1,9 Of the treatments for DPN, electrodesiccation and laser therapy routinely are used.10 

The efficacy of electrodessication and potassium titanyl phosphate (KTP) laser were assessed in a randomized, investigatorblinded split-face study.11 Both modalities received high improvement ratings, with the results favoring the KTP laser. The patients (most of whom were Black) reported that KTP laser was more effective but more painful than electrodessication (P =.002).11 In another randomized study, patients received 3 treatments—electrodessication, pulsed dye laser, and curettage—for select DPN papules.10 There was no difference in the degree of clearance, cosmetic outcome, or postinflammatory hyperpigmentation between the 3 modalities, but patients found the laser to be the most painful. 

It is important to exercise caution when using abrasive methods (eg, laser therapy, electrodesiccation, curettage) in patients with darker skin tones because of the increased risk for postinflammatory pigment alteration.1,2,12 Adverse effects of treatment are a top concern in the management of DPN.5,13 While cryotherapy is a preferred treatment of SK in lighter skin tones, it generally is avoided for DPN in darker skin types because melanocyte destruction can lead to cosmetically unsatisfactory and easily visible depigmentation.9 

To mitigate postprocedural adverse effects, proper aftercare can promote wound healing and minimize postinflammatory pigment alteration. In one split-face study of Black patients, 2 DPN papules were removed from each side of the face using fine-curved surgical scissors.14 Next, a petrolatum-based ointment and an antibiotic ointment with polymyxin B sulfate/bacitracin zinc was applied twice daily for 21 days to opposite sides of the face. Patients did not develop infection, tolerated both treatments well, and demonstrated improved general wound appearance according to investigator- rated clinical assessment.14 Other reported postprocedural approaches include using topical agents with ingredients shown to improve hyperpigmentation (eg, niacinamide, azelaic acid) as well as photoprotection.12 

HEALTH DISPARITY HIGHLIGHT 

While DPN is benign, it can have adverse psychosocial effects on patients. A study in Senegal revealed that 60% (19/30) of patients with DPN experienced anxiety related to their condition, while others noted that DPN hindered their social relationships.13 In one US study of 50 Black patients with DPN, there was a moderate effect on quality of life, and 36% (18/50) of patients had the lesions removed. However, of the treated patients, 67% (12/18) reported few—if any—symptoms prior to removal.5 Although treatment of DPN is widely considered a cosmetic procedure, therapeutic management can address— and may improve—mental health in patients with skin of color.1,5,13 Despite the high prevalence of DPN in patients with darker skin tones, data on treatment frequency and insurance coverage are not widely available, thus limiting our understanding of treatment accessibility and economic burden. 

References
  1. Frazier WT, Proddutur S, Swope K. Common dermatologic conditions in skin of color. Am Fam Physician. 2023;107:26-34. 
  2. Metin SA, Lee BW, Lambert WC, et al. Dermatosis papulosa nigra: a clinically and histopathologically distinct entity. Clin Dermatol. 2017;35:491-496. 
  3. Braun RP, Ludwig S, Marghoob AA. Differential diagnosis of seborrheic keratosis: clinical and dermoscopic features. J Drugs Dermatol. 2017;16:835-842. 
  4. Sun MD, Halpern AC. Advances in the etiology, detection, and clinical management of seborrheic keratoses. Dermatology. 2022;238:205-217. 
  5. Uwakwe LN, De Souza B, Subash J, et al. Dermatosis papulosa nigra: a quality of life survey study. J Clin Aesthet Dermatol. 2020;13:17-19. 
  6. Bhat RM, Patrao N, Monteiro R, et al. A clinical, dermoscopic, and histopathological study of dermatosis papulosa nigra (DPN)—an Indian perspective. Int J Dermatol. 2017;56:957-960. 
  7. Karampinis E, Georgopoulou KE, Kampra E, et al. Clinical and dermoscopic patterns of basal cell carcinoma and its mimickers in skin of color: a practical summary. Medicina (Kaunas). 2024;60:1386. 
  8. Gorai S, Ahmad S, Raza SSM, et al. Update of pathophysiology and treatment options of seborrheic keratosis. Dermatol Ther. 2022;35:E15934. 
  9. Jain S, Caire H, Haas CJ. Management of dermatosis papulosa nigra: a systematic review. Int J Dermatol. Published online October 4, 2024. 
  10. Garcia MS, Azari R, Eisen DB. Treatment of dermatosis papulosa nigra in 10 patients: a comparison trial of electrodesiccation, pulsed dye laser, and curettage. Dermatol Surg. 2010;36:1968-1972. 
  11. Kundu RV, Joshi SS, Suh KY, et al. Comparison of electrodesiccation and potassium-titanyl-phosphate laser for treatment of dermatosis papulosa nigra. Dermatol Surg. 2009;35:1079-1083. 
  12. Markiewicz E, Karaman-Jurukovska N, Mammone T, et al. Post-inflammatory hyperpigmentation in dark skin: molecular mechanism and skincare implications. Clin Cosmet Investig Dermatol. 2022;15:2555-2565. 
  13. Niang SO, Kane A, Diallo M, et al. Dermatosis papulosa nigra in Dakar, Senegal. Int J Dermatol. 2007;46(suppl 1):45-47. 
  14. Taylor SC, Averyhart AN, Heath CR. Postprocedural wound-healing efficacy following removal of dermatosis papulosa nigra lesions in an African American population: a comparison of a skin protectant ointment and a topical antibiotic. J Am Acad Dermatol. 2011;64(suppl 3):S30-S35.
References
  1. Frazier WT, Proddutur S, Swope K. Common dermatologic conditions in skin of color. Am Fam Physician. 2023;107:26-34. 
  2. Metin SA, Lee BW, Lambert WC, et al. Dermatosis papulosa nigra: a clinically and histopathologically distinct entity. Clin Dermatol. 2017;35:491-496. 
  3. Braun RP, Ludwig S, Marghoob AA. Differential diagnosis of seborrheic keratosis: clinical and dermoscopic features. J Drugs Dermatol. 2017;16:835-842. 
  4. Sun MD, Halpern AC. Advances in the etiology, detection, and clinical management of seborrheic keratoses. Dermatology. 2022;238:205-217. 
  5. Uwakwe LN, De Souza B, Subash J, et al. Dermatosis papulosa nigra: a quality of life survey study. J Clin Aesthet Dermatol. 2020;13:17-19. 
  6. Bhat RM, Patrao N, Monteiro R, et al. A clinical, dermoscopic, and histopathological study of dermatosis papulosa nigra (DPN)—an Indian perspective. Int J Dermatol. 2017;56:957-960. 
  7. Karampinis E, Georgopoulou KE, Kampra E, et al. Clinical and dermoscopic patterns of basal cell carcinoma and its mimickers in skin of color: a practical summary. Medicina (Kaunas). 2024;60:1386. 
  8. Gorai S, Ahmad S, Raza SSM, et al. Update of pathophysiology and treatment options of seborrheic keratosis. Dermatol Ther. 2022;35:E15934. 
  9. Jain S, Caire H, Haas CJ. Management of dermatosis papulosa nigra: a systematic review. Int J Dermatol. Published online October 4, 2024. 
  10. Garcia MS, Azari R, Eisen DB. Treatment of dermatosis papulosa nigra in 10 patients: a comparison trial of electrodesiccation, pulsed dye laser, and curettage. Dermatol Surg. 2010;36:1968-1972. 
  11. Kundu RV, Joshi SS, Suh KY, et al. Comparison of electrodesiccation and potassium-titanyl-phosphate laser for treatment of dermatosis papulosa nigra. Dermatol Surg. 2009;35:1079-1083. 
  12. Markiewicz E, Karaman-Jurukovska N, Mammone T, et al. Post-inflammatory hyperpigmentation in dark skin: molecular mechanism and skincare implications. Clin Cosmet Investig Dermatol. 2022;15:2555-2565. 
  13. Niang SO, Kane A, Diallo M, et al. Dermatosis papulosa nigra in Dakar, Senegal. Int J Dermatol. 2007;46(suppl 1):45-47. 
  14. Taylor SC, Averyhart AN, Heath CR. Postprocedural wound-healing efficacy following removal of dermatosis papulosa nigra lesions in an African American population: a comparison of a skin protectant ointment and a topical antibiotic. J Am Acad Dermatol. 2011;64(suppl 3):S30-S35.
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Trump Administration Review of Psychiatric Meds Raises Concerns

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The Trump administration’s plans to study the “threat” posed by psychiatric medications in children have medical societies and mental health professionals concerned that the administration may be considering restrictions on the use of psychotropic drugs in pediatric patients.

An executive order signed last week created the “Make American Healthy Again Commission” to investigate the nation’s “escalating health crisis,” particularly in child health. Recently confirmed Secretary of the US Department of Health and Human Services Robert F. Kennedy Jr. will chair the effort.

As part of its investigation, the executive order directed the commission to assess “the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, mood stabilizers, stimulants, and weight-loss drugs.”

A report on the commission’s findings is due in a little less than 100 days. Eighty days later, the commission must submit recommendations for federal action.

Although who the commission members are and the scope of its work is unclear, the language in the executive order — namely the implication that the Trump administration views psychotropic medication as a “threat” to children — was enough to prompt psychiatrists from across the country to contact the American Psychiatric Association (APA) about possible limitations on the use of psychotropic medications in pediatric patients.

“It’s concerning and surprising that some of our nation’s most vulnerable children who need these treatments to participate fully in life would be under scrutiny in this way,” Marketa Wills, MD, MBA, chief executive officer and medical director for the APA, told this news organization.

“If these medications are under threat and children decompensate that would not be good from a public health perspective, for the healthcare system or for the families we serve,” Wills said.

 

Past Comments Fuel Distress

Past comments by the commission chair have only fueled distress over the commission’s goals. Kennedy has long expressed skepticism about antidepressants, especially (SSRIs), questioning their safety and suggesting they are as addictive as heroin. 

“I know people, including members of my family, who’ve had a much worse time getting off of SSRIs than they have getting off of heroin,” Kennedy said during his Senate confirmation hearing in late January.

But there is no evidence to suggest SSRIs or other antidepressants are addictive, Leslie A. Hulvershorn, MD, chair and associate professor of psychiatry at Indiana University School of Medicine, told this news organization.

“They don’t work in the systems of the brain that drive addiction. A large amount of research suggests that they are safe to take for a long time,” she said. “I suspect the confusion comes from the difference between it not being wise to come off of the medication, because of a concern for relapse of a psychiatric illness, and some transient discomfort from abruptly stopping SSRIs without tapering them off versus being addicted to it, like heroin.”

During the hearing, Kennedy was also asked to respond to comments he made during a 2023 livestream on X in which he claimed that the use of antidepressants have contributed to the increase in school shootings in the United States.

“I am also going to look very closely at the role of psychiatric drugs in these events and there are no good studies right now that should have been done years ago on this issue because there is a tremendous circumstantial evidence that SSRIs and benzos and other drugs are doing this,” he said in the livestream. 

Research has shown that there is no link between school shootings and antidepressant use.

In a 2024 interview on the Latino Capitalist podcast, Kennedy said that he wanted create “wellness farms” for adults addicted to illicit drugs and children who take antidepressants or stimulants for ADHD could be “reparented.”

“The views on those wellness farms are concerning for us here at the American Psychiatric Association. It remains to be seen if he brings that back up in his new role at HHS. There is currently no evidence of their efficacy,” Wills said.

 

Fear Is a ‘Real Concern’

These controversial comments, combined with the commission’s charge to investigate the potential “threat” psychotropic medications pose to children, worry clinicians and families fear that access to medication could be restricted.

“Psychiatrists and patients are very concerned about the risk these statements may pose,” Hulvershorn said.

“Certainly, there is evidence that psychotropic medications are overprescribed, particularly in children who are in state care — like wards of the state — and who are part of Medicaid programs, but there is tremendous overall benefit associated with psychotropic medications in youth and adults. They are lifesaving and game changing in many instances,” she added.

Psychiatrists who’ve contacted the APA since last week’s announcement echo Hulvershorn’s comments. 

“The fear is the real concern,” Wills said. “No parent takes the decision lightly to put their child on medication. With all interventions, particularly with children, there are risks and benefits that must be carefully weighed. The best person to weigh those risks and benefits is the child and adolescent psychiatrist, in conjunction with the child’s parents.”

The focus on medication also overlooks the fact that psychosocial interventions — not medication — are first-line treatment for children with mental health issues and that guidelines recommend medication be used alongside nonpharmacological therapy.

“Extensive research, including large national multi-site studies, have examined the most effective ways to reduce psychological symptoms among youth, including anxiety, depression, and ADHD. Results consistently reveal that both psychotropic medications and psychological interventions can offer significant improvements, often in combination,” Mitch Prinstein, PhD, chief of psychology strategy and integration at the American Psychological Association, told this news organization. 

“Given the substantial challenges for many in gaining access to psychotherapy and a national shortage of licensed psychologists, reducing access to medications would undoubtedly have a debilitating effect of the already concerning youth mental health crisis,” Prinstein said. 

 

A Seat at The Table

While the launch of the commission has left some feeling uneasy, experts agree that a national focus on children’s mental health is needed.

The APA would “welcome an opportunity to be part of this national conversation following the evidence base, following settled science that shows when and how these medications are effective and helpful for children and families,” said Wills. “We also think it’s very important that child and adolescent psychiatrists be at the table for this national conversation on behalf of the families they serve.” 

In a joint letter with the APA, officials with the American Academy of Child and Adolescent Psychiatry also expressed interest in playing a role in the commission’s work. 

“We are in the middle of a mental health crisis, with a record number of Americans struggling with mental health and substance use disorders. We strongly urge you to prioritize strengthening the ability to respond to an increasing demand for psychiatric services, especially for children,” the letter stated.

Indeed, looking beyond just the use of psychotropic medications is vital to the success of any strategy to address the youth mental health crisis, Hulvershorn noted. 

“There are already many programs underway to examine the overprescribing. In my view, the lack of supports by payors for behavioral interventions, such as evidence-based family interventions, psychotherapies, etc., is the major driver for overuse of medications,” she said.

“Every pediatrician and child psychiatrist I know would rather try a behavioral intervention with a family first, but those are services that our systems do not financially support well and are, thus, underdeveloped, and very difficult to access,” Hulvershorn added.

More funding for evidence-based interventions — both behavioral and pharmacological — is desperately needed, she said. Support for workforce development should also be a part of any proposed solution. 

“Adequate and responsible funding in all of those areas is needed, but we have some low hanging fruit in terms of figuring out how to just deliver the interventions that science has shown us do work,” Hulvershorn said. “Many of those interventions don’t involve medication and I think every expert in the field would be glad to see more effort put into system reform to better deliver interventions that work to youth and their families.”

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

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The Trump administration’s plans to study the “threat” posed by psychiatric medications in children have medical societies and mental health professionals concerned that the administration may be considering restrictions on the use of psychotropic drugs in pediatric patients.

An executive order signed last week created the “Make American Healthy Again Commission” to investigate the nation’s “escalating health crisis,” particularly in child health. Recently confirmed Secretary of the US Department of Health and Human Services Robert F. Kennedy Jr. will chair the effort.

As part of its investigation, the executive order directed the commission to assess “the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, mood stabilizers, stimulants, and weight-loss drugs.”

A report on the commission’s findings is due in a little less than 100 days. Eighty days later, the commission must submit recommendations for federal action.

Although who the commission members are and the scope of its work is unclear, the language in the executive order — namely the implication that the Trump administration views psychotropic medication as a “threat” to children — was enough to prompt psychiatrists from across the country to contact the American Psychiatric Association (APA) about possible limitations on the use of psychotropic medications in pediatric patients.

“It’s concerning and surprising that some of our nation’s most vulnerable children who need these treatments to participate fully in life would be under scrutiny in this way,” Marketa Wills, MD, MBA, chief executive officer and medical director for the APA, told this news organization.

“If these medications are under threat and children decompensate that would not be good from a public health perspective, for the healthcare system or for the families we serve,” Wills said.

 

Past Comments Fuel Distress

Past comments by the commission chair have only fueled distress over the commission’s goals. Kennedy has long expressed skepticism about antidepressants, especially (SSRIs), questioning their safety and suggesting they are as addictive as heroin. 

“I know people, including members of my family, who’ve had a much worse time getting off of SSRIs than they have getting off of heroin,” Kennedy said during his Senate confirmation hearing in late January.

But there is no evidence to suggest SSRIs or other antidepressants are addictive, Leslie A. Hulvershorn, MD, chair and associate professor of psychiatry at Indiana University School of Medicine, told this news organization.

“They don’t work in the systems of the brain that drive addiction. A large amount of research suggests that they are safe to take for a long time,” she said. “I suspect the confusion comes from the difference between it not being wise to come off of the medication, because of a concern for relapse of a psychiatric illness, and some transient discomfort from abruptly stopping SSRIs without tapering them off versus being addicted to it, like heroin.”

During the hearing, Kennedy was also asked to respond to comments he made during a 2023 livestream on X in which he claimed that the use of antidepressants have contributed to the increase in school shootings in the United States.

“I am also going to look very closely at the role of psychiatric drugs in these events and there are no good studies right now that should have been done years ago on this issue because there is a tremendous circumstantial evidence that SSRIs and benzos and other drugs are doing this,” he said in the livestream. 

Research has shown that there is no link between school shootings and antidepressant use.

In a 2024 interview on the Latino Capitalist podcast, Kennedy said that he wanted create “wellness farms” for adults addicted to illicit drugs and children who take antidepressants or stimulants for ADHD could be “reparented.”

“The views on those wellness farms are concerning for us here at the American Psychiatric Association. It remains to be seen if he brings that back up in his new role at HHS. There is currently no evidence of their efficacy,” Wills said.

 

Fear Is a ‘Real Concern’

These controversial comments, combined with the commission’s charge to investigate the potential “threat” psychotropic medications pose to children, worry clinicians and families fear that access to medication could be restricted.

“Psychiatrists and patients are very concerned about the risk these statements may pose,” Hulvershorn said.

“Certainly, there is evidence that psychotropic medications are overprescribed, particularly in children who are in state care — like wards of the state — and who are part of Medicaid programs, but there is tremendous overall benefit associated with psychotropic medications in youth and adults. They are lifesaving and game changing in many instances,” she added.

Psychiatrists who’ve contacted the APA since last week’s announcement echo Hulvershorn’s comments. 

“The fear is the real concern,” Wills said. “No parent takes the decision lightly to put their child on medication. With all interventions, particularly with children, there are risks and benefits that must be carefully weighed. The best person to weigh those risks and benefits is the child and adolescent psychiatrist, in conjunction with the child’s parents.”

The focus on medication also overlooks the fact that psychosocial interventions — not medication — are first-line treatment for children with mental health issues and that guidelines recommend medication be used alongside nonpharmacological therapy.

“Extensive research, including large national multi-site studies, have examined the most effective ways to reduce psychological symptoms among youth, including anxiety, depression, and ADHD. Results consistently reveal that both psychotropic medications and psychological interventions can offer significant improvements, often in combination,” Mitch Prinstein, PhD, chief of psychology strategy and integration at the American Psychological Association, told this news organization. 

“Given the substantial challenges for many in gaining access to psychotherapy and a national shortage of licensed psychologists, reducing access to medications would undoubtedly have a debilitating effect of the already concerning youth mental health crisis,” Prinstein said. 

 

A Seat at The Table

While the launch of the commission has left some feeling uneasy, experts agree that a national focus on children’s mental health is needed.

The APA would “welcome an opportunity to be part of this national conversation following the evidence base, following settled science that shows when and how these medications are effective and helpful for children and families,” said Wills. “We also think it’s very important that child and adolescent psychiatrists be at the table for this national conversation on behalf of the families they serve.” 

In a joint letter with the APA, officials with the American Academy of Child and Adolescent Psychiatry also expressed interest in playing a role in the commission’s work. 

“We are in the middle of a mental health crisis, with a record number of Americans struggling with mental health and substance use disorders. We strongly urge you to prioritize strengthening the ability to respond to an increasing demand for psychiatric services, especially for children,” the letter stated.

Indeed, looking beyond just the use of psychotropic medications is vital to the success of any strategy to address the youth mental health crisis, Hulvershorn noted. 

“There are already many programs underway to examine the overprescribing. In my view, the lack of supports by payors for behavioral interventions, such as evidence-based family interventions, psychotherapies, etc., is the major driver for overuse of medications,” she said.

“Every pediatrician and child psychiatrist I know would rather try a behavioral intervention with a family first, but those are services that our systems do not financially support well and are, thus, underdeveloped, and very difficult to access,” Hulvershorn added.

More funding for evidence-based interventions — both behavioral and pharmacological — is desperately needed, she said. Support for workforce development should also be a part of any proposed solution. 

“Adequate and responsible funding in all of those areas is needed, but we have some low hanging fruit in terms of figuring out how to just deliver the interventions that science has shown us do work,” Hulvershorn said. “Many of those interventions don’t involve medication and I think every expert in the field would be glad to see more effort put into system reform to better deliver interventions that work to youth and their families.”

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

The Trump administration’s plans to study the “threat” posed by psychiatric medications in children have medical societies and mental health professionals concerned that the administration may be considering restrictions on the use of psychotropic drugs in pediatric patients.

An executive order signed last week created the “Make American Healthy Again Commission” to investigate the nation’s “escalating health crisis,” particularly in child health. Recently confirmed Secretary of the US Department of Health and Human Services Robert F. Kennedy Jr. will chair the effort.

As part of its investigation, the executive order directed the commission to assess “the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, mood stabilizers, stimulants, and weight-loss drugs.”

A report on the commission’s findings is due in a little less than 100 days. Eighty days later, the commission must submit recommendations for federal action.

Although who the commission members are and the scope of its work is unclear, the language in the executive order — namely the implication that the Trump administration views psychotropic medication as a “threat” to children — was enough to prompt psychiatrists from across the country to contact the American Psychiatric Association (APA) about possible limitations on the use of psychotropic medications in pediatric patients.

“It’s concerning and surprising that some of our nation’s most vulnerable children who need these treatments to participate fully in life would be under scrutiny in this way,” Marketa Wills, MD, MBA, chief executive officer and medical director for the APA, told this news organization.

“If these medications are under threat and children decompensate that would not be good from a public health perspective, for the healthcare system or for the families we serve,” Wills said.

 

Past Comments Fuel Distress

Past comments by the commission chair have only fueled distress over the commission’s goals. Kennedy has long expressed skepticism about antidepressants, especially (SSRIs), questioning their safety and suggesting they are as addictive as heroin. 

“I know people, including members of my family, who’ve had a much worse time getting off of SSRIs than they have getting off of heroin,” Kennedy said during his Senate confirmation hearing in late January.

But there is no evidence to suggest SSRIs or other antidepressants are addictive, Leslie A. Hulvershorn, MD, chair and associate professor of psychiatry at Indiana University School of Medicine, told this news organization.

“They don’t work in the systems of the brain that drive addiction. A large amount of research suggests that they are safe to take for a long time,” she said. “I suspect the confusion comes from the difference between it not being wise to come off of the medication, because of a concern for relapse of a psychiatric illness, and some transient discomfort from abruptly stopping SSRIs without tapering them off versus being addicted to it, like heroin.”

During the hearing, Kennedy was also asked to respond to comments he made during a 2023 livestream on X in which he claimed that the use of antidepressants have contributed to the increase in school shootings in the United States.

“I am also going to look very closely at the role of psychiatric drugs in these events and there are no good studies right now that should have been done years ago on this issue because there is a tremendous circumstantial evidence that SSRIs and benzos and other drugs are doing this,” he said in the livestream. 

Research has shown that there is no link between school shootings and antidepressant use.

In a 2024 interview on the Latino Capitalist podcast, Kennedy said that he wanted create “wellness farms” for adults addicted to illicit drugs and children who take antidepressants or stimulants for ADHD could be “reparented.”

“The views on those wellness farms are concerning for us here at the American Psychiatric Association. It remains to be seen if he brings that back up in his new role at HHS. There is currently no evidence of their efficacy,” Wills said.

 

Fear Is a ‘Real Concern’

These controversial comments, combined with the commission’s charge to investigate the potential “threat” psychotropic medications pose to children, worry clinicians and families fear that access to medication could be restricted.

“Psychiatrists and patients are very concerned about the risk these statements may pose,” Hulvershorn said.

“Certainly, there is evidence that psychotropic medications are overprescribed, particularly in children who are in state care — like wards of the state — and who are part of Medicaid programs, but there is tremendous overall benefit associated with psychotropic medications in youth and adults. They are lifesaving and game changing in many instances,” she added.

Psychiatrists who’ve contacted the APA since last week’s announcement echo Hulvershorn’s comments. 

“The fear is the real concern,” Wills said. “No parent takes the decision lightly to put their child on medication. With all interventions, particularly with children, there are risks and benefits that must be carefully weighed. The best person to weigh those risks and benefits is the child and adolescent psychiatrist, in conjunction with the child’s parents.”

The focus on medication also overlooks the fact that psychosocial interventions — not medication — are first-line treatment for children with mental health issues and that guidelines recommend medication be used alongside nonpharmacological therapy.

“Extensive research, including large national multi-site studies, have examined the most effective ways to reduce psychological symptoms among youth, including anxiety, depression, and ADHD. Results consistently reveal that both psychotropic medications and psychological interventions can offer significant improvements, often in combination,” Mitch Prinstein, PhD, chief of psychology strategy and integration at the American Psychological Association, told this news organization. 

“Given the substantial challenges for many in gaining access to psychotherapy and a national shortage of licensed psychologists, reducing access to medications would undoubtedly have a debilitating effect of the already concerning youth mental health crisis,” Prinstein said. 

 

A Seat at The Table

While the launch of the commission has left some feeling uneasy, experts agree that a national focus on children’s mental health is needed.

The APA would “welcome an opportunity to be part of this national conversation following the evidence base, following settled science that shows when and how these medications are effective and helpful for children and families,” said Wills. “We also think it’s very important that child and adolescent psychiatrists be at the table for this national conversation on behalf of the families they serve.” 

In a joint letter with the APA, officials with the American Academy of Child and Adolescent Psychiatry also expressed interest in playing a role in the commission’s work. 

“We are in the middle of a mental health crisis, with a record number of Americans struggling with mental health and substance use disorders. We strongly urge you to prioritize strengthening the ability to respond to an increasing demand for psychiatric services, especially for children,” the letter stated.

Indeed, looking beyond just the use of psychotropic medications is vital to the success of any strategy to address the youth mental health crisis, Hulvershorn noted. 

“There are already many programs underway to examine the overprescribing. In my view, the lack of supports by payors for behavioral interventions, such as evidence-based family interventions, psychotherapies, etc., is the major driver for overuse of medications,” she said.

“Every pediatrician and child psychiatrist I know would rather try a behavioral intervention with a family first, but those are services that our systems do not financially support well and are, thus, underdeveloped, and very difficult to access,” Hulvershorn added.

More funding for evidence-based interventions — both behavioral and pharmacological — is desperately needed, she said. Support for workforce development should also be a part of any proposed solution. 

“Adequate and responsible funding in all of those areas is needed, but we have some low hanging fruit in terms of figuring out how to just deliver the interventions that science has shown us do work,” Hulvershorn said. “Many of those interventions don’t involve medication and I think every expert in the field would be glad to see more effort put into system reform to better deliver interventions that work to youth and their families.”

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

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Utilization and Cost of Veterans Health Administration Referrals to Community Care-Based Physical Therapy

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Utilization and Cost of Veterans Health Administration Referrals to Community Care-Based Physical Therapy

 

The Veterans Health Administration (VHA) is the largest US integrated health system, providing care to veterans through VHA and non-VHA practitioners and facilities.1,2 Providing high-quality, timely, and veteran-centric care remains a priority for the VHA. Legislative efforts have expanded opportunities for eligible veterans to receive care in the community purchased by VHA, known as community care (CC).1 The Veterans Access, Choice, and Accountability Act of 2014 came in response to reports of long wait times and drive times for patients.3-5 The MISSION Act of 2018 expanded access to CC by streamlining it and broadening eligibility criteria, especially for veterans in rural communities who often experience more barriers in accessing care than veterans living in urban communities.1,6-10 Since the implementation of the Choice and MISSION Acts, > 2.7 million veterans have received care through community practitioners within the VHA CC network.11

Background

Increased access to CC could benefit veterans living in rural communities by increasing care options and circumventing challenges to accessing VHA care (ie, geographic, transportation, and distance barriers, practitioner and specialist shortages, and hospital closures). 5,9,10,12,13 However, health care system deficits in rural areas could also limit CC effectiveness for veterans living in those communities. 3 Other challenges posed by using CC include care coordination, information sharing, care continuity, delayed payments to CC practitioners, and mixed findings regarding CC quality.5,8,13,14 VHA practitioners are specifically trained to meet the multifaceted needs unique to veterans’ health and subculture, training CC practitioners may not receive.5,15

CC offers services for primary care and a broad range of specialties, including rehabilitation services such as physical therapy (PT).6 PT is used for the effective treatment of various conditions veterans experience and promote wellbeing and independence.16 US Department of Veterans Affairs (VA) databases reveal a high prevalence of veterans receiving PT services through CC; PT is one of the most frequently used CC outpatient specialty services by veterans living in rural communities.14,17

Telerehabitltation Enterprisewide Initiative

VHA has greatly invested in delivering care virtually, especially for veterans living in rural communities.18 In 2017, the VHA Office of Rural Health funded the Telerehabilitation Enterprise-Wide Initiative (TR-EWI) in partnership with the Physical Medicine and Rehabilitation Services national program office to increase access to specialized rehabilitation services for veterans living in rural communities by leveraging telehealth technologies.18-21 This alternative mode of health care delivery allows clinicians to overcome access barriers by delivering rehabilitation therapies directly to veterans' homes or nearby community-based outpatient clinics. TR-EWI was conceived as a hub-and-spoke model, where rehabilitation expertise at the hub was virtually delivered to spoke sites that did not have in-house expertise. In subsequent years, the TR-EWI also evolved to provide targeted telerehabilitation programs within rural-serving community-based outpatient clinics, including PT as a predominant service.19,20

As TR-EWI progressed—and in conjunction with the uptake of telehealth across VHA during the COVID-19 pandemic—there has been increased focus on PT telerehabilitation, especially for the 4.6 million veterans in rural communities.18,22,23 Because health care delivery system deficits in rural areas could limit the effective use of CC, many TR-EWI sites hope to reduce their CC referrals by providing telehealth PT services to veterans who might otherwise need to be referred to CC. This strategy aligns with VHA goals of providing high-quality and timely care. To better understand opportunities for programs like TR-EWI to provide rehabilitation services for veterans and reduce care sent to the community, research that examines CC referral trends for PT over time is warranted.

This study examines CC from a rehabilitation perspective with a focus on CC referral trends for PT, specifically for Veterans Integrated Service Networks (VISNs) where TREWI sites are located. The study’s objectives were to describe rehabilitation PT services being referred to CC and examine associated CC costs for PT services. Two research questions guided the study. First, what are the utilization trends for CC PT referrals from fiscal year (FY) 2019 to FY 2022? Secondly, what is the cost breakdown of CC for PT referrals from FY 2020 to FY 2022?

Methods

This study was conducted by a multidisciplinary team comprised of public health, disability, rehabilitation counseling, and PT professionals. It was deemed a quality improvement project under VA guidance and followed the SQUIRE guidelines for quality improvement reporting.24,25 The study used the VA Common Operating Platform (Palantir) to obtain individual-level CC referral data from the HealthShare Referral Manager (HSRM) database and consult data from the Computerized Patient Record System. Palantir is used to store and integrate VA data derived from the VA Corporate Data Warehouse and VHA Support Service Center. Referrals are authorizations for care to be delivered by a CC practitioner.

TR-EWI is comprised of 7 sites: VISN 2, VISN 4, VISN 8, VISN 12, VISN 15, VISN 19, and VISN 22. Each site provides telerehabilitation services with an emphasis on reaching veterans living in rural communities. We joined the referrals and consults cubes in Palantir to extract PT referrals for FY 2019 to FY 2022 for the 7 VISNs with TR-EWI sites and obtain referral-specific information and demographic characteristics. 26 Data were extracted in October 2022.

The VHA Community Care Referral Dashboard (CC Dashboard) provided nonindividual level CC cost data.27 The CC Dashboard provides insights into the costs of CC services for VHA enrollees by category of care, standardized episode of care, and eligibility. Data are based on nationallevel HSRM referrals that are not suspended or linked to a canceled or discontinued consult. Data were aggregated by VISN. The dashboard only includes referrals dating back to FY 2020; therefore, PT data from FY 2020 through FY 2022 for VISNs with TR-EWI sites were collected. Data were extracted in December 2022.

This study examined CC referrals, station name, eligibility types, clinical diagnoses (International Classification of Diseases, Tenth Revision codes), and demographic information in the Palantir dataset. Six eligibility criteria can qualify a veteran to receive CC.28 Within clinical diagnoses, the variable of interest was the provisional diagnosis. Patient demographics included age, gender, and rurality of residence, as determined by the Rural-Urban Commuting Area system.29,30 Rural and highly rural categories were combined for analysis. For the CC cost dataset, this study examined CC referrals, referral cost, and eligibility type.

Analysis

For the first research question, we examined referral data from FY 2019 to FY 2022 using the Palantir dataset, performed descriptive statistical analysis for all variables, and analyzed data to identify trends. Descriptive statistics were completed using IBM SPSS Statistics for Windows Version 29.0.0.0.

A qualitative analysis of provisional diagnosis data revealed what is being referred to CC for PT. A preliminary overview of provisional diagnosis data was conducted to familiarize coders with the data. We developed a coding framework to categorize diagnoses based on anatomical location, body structure, and clinical areas of interest. Data were reviewed individually and grouped into categories within the coding framework before meeting as a team to achieve group consensus on categorization. We then totaled the frequency of occurrence for provisional diagnoses within each category. Qualitative analyses were completed using Microsoft Excel.

For the second research question, the study used the CC cost dataset to examine the cost breakdown of CC PT referrals from FY 2020 to FY 2022. We calculated the number and cost of PT referrals across eligibility groups for each FY and VISN. Data were analyzed using SPSS to identify cost trends.

Results

There were 344,406 referrals to CC for PT from FY 2019 to FY 2022 for the 7 VISNs analyzed (Table 1). Of these, 22.5% were from FY 2019, 19.1% from FY 2020, 28.2% from FY 2021, and 30.3% from FY 2022. VISN 8 and VISN 22 reported the most overall PT referrals, with VISN 8 comprising 22.2% and VISN 22 comprising 18.1% of all referrals. VISN 2 reported the least overall referrals (3.7%). VISN 4 and VISN 12 had decreases in referrals over time. VISN 2 and VISN 15 had decreases in referrals from FY 2019 to FY 2021 and slight increases from FY 2021 to FY 2022. VISN 19 and VISN 22 both saw slight increases from FY 2019 to FY 2020 and substantial increases from FY 2020 to FY 2022, with FY 2022 accounting for 40.0% and 42.3% of all referrals for VISN 19 and VISN 20, respectively (Figure 1).

0225FED-ePT-T10225FED-ePT-F1

For FY 2019 and FY 2020, VISN 8 had the highest percentage of referrals (26.7% and 23.2%, respectively), whereas VISN 22 was among the lowest (7.3% and 11.4%, respectively). However, for FY 2021 and FY 2022, VISN 22 reported the highest percentage of referrals (23.5% and 25.3%, respectively) compared to all other VISNs. VISN 2 consistently reported the lowest percentage of referrals across all years.

There were 56 stations analyzed across the 7 VISNs (Appendix 1). Nine stations each accounted for ≥ 3.0% of the total PT referrals and only 2 stations accounted for > 5.0% of referrals. Orlando, Florida (6.0%), Philadelphia, Pennsylvania (5.2%), Tampa, Florida (4.9%), Aurora, Colorado (4.9%), and Gainesville, Florida (4.4%) reported the top 5 highest referrals, with 3 being from VISN 8 (Orlando, Tampa, Gainesville). Stations with the lowest reported referrals were all in VISN 2 in New York: The Bronx, (0%), New York Harbor (0%), Hudson Valley (0.1%) and Finger Lakes (0.2%).

0225FED-ePT-A1
Rurality

Urban stations comprised 56.2% and rural stations comprised 39.8% of PT CC referrals, while 0.2% of referrals were from insular isle US territories: Guam, American Samoa, Northern Marianas, and the Virgin Islands. The sample had missing or unknown data for 3.8% of referrals. FY 2022 had the largest difference in rural and urban referrals. Additionally, there was an overall trend of more referrals over time for rural and urban, with a large increase in rural (+40.0%) and urban (+62.7%) referrals from FY 2020 to FY 2021 and a modest increase from FY 2021 to FY 2022 (+5.2% for rural and +9.1% for urban). There was a decrease in rural (-7.0%) and urban (-3.5%) referrals from FY 2019 to FY 2020 (Figure 2).

0225FED-ePT-F2

There were differences in referrals by rurality and VISN (Table 2). VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals, whereas VISN 4, VISN 8, and VISN 22 reported more urban than rural referrals. VISN 2 reported similar numbers for both, with slightly more urban than rural referrals. When reviewing trends over time for each FY, VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals and VISN 4, VISN 8, and VISN 22 had more urban than rural referrals. In FY 2019 and FY 2020, VISN 2 reported slightly more urban than rural referrals but almost the same number of referrals in FY 2021 and FY 2022 (Appendix 2).

0225FED-ePT-T20225FED-ePT-A2
Demographics

The mean (SD) age was 61.2 (15.8) years (range, 20-105). Most PT CC referrals were for veterans aged 70 to 79 years (26.9%), followed by 60 to 69 years (20.7%), and 50 to 59 years (16.4%) (Appendix 3). Trends were consistent across VISNs. There was less of a difference between rural and urban referral percentages as the population aged. Veterans aged < 49 years residing in more urban areas accounted for more referrals to CC compared to their rural counterparts. This difference was less apparent in the 70 to 79 years and 80 to 89 years age brackets.

0225FED-ePT-A3

Most PT CC referrals (81.2%) were male and 14.8% were female. About 3.6% of referral data were missing sex information, and there was a smaller difference between male veterans living in rural communities and male veterans living in urban communities compared with female veterans. A total of 42.9% of male veterans resided in rural areas compared to 56.8% in urban areas; 32.7% of female veterans resided in rural areas compared to 66.9% in urban areas (Appendix 3).

Other Criteria

Of the 334,406 referrals, 114,983 (34.4%) had eligibility data, mostly from FY 2021 and FY 2022 (Table 3). Available eligibility data were likely affected by the MISSION Act and new regulations for reporting CC eligibility. Distance (33.4%) was the most common eligibility criteria, followed by timeliness of care (28.8%), and best medical interest (19.8%); 40.4% were rural and 59.5% were urban. Distance (55.4%) was most common for rural veterans, while timeliness of care (39.7%) was most common for urban veterans. For both groups, the second most common eligibility reason was best medical interest (Appendix 4).

0225FED-ePT-T30225FED-ePT-A4

Bone, joint, or soft tissue disorders were common diagnoses, with 25.2% located in the lower back, 14.7% in the shoulder, and 12.8% in the knee (Appendix 5). Amputations of the upper and lower limbs, fractures, cancer-related diagnoses, integumentary system disorders, thoracic and abdominal injuries and disorders, and other medical and mental health conditions each accounted for < 1% of the total diagnoses.

0225FED-ePT-A5
Costs

At time of analysis, the CC Dashboard had cost data available for 200,204 CC PT referrals from FY 2020 to FY 2022. The difference in referral numbers for the 2 datasets is likely attributed to several factors: CC cost data is exclusively from the HSRM, whereas Palantir includes other data sources; how VA cleans data pulled into Palantir; how the CC Dashboard algorithm populates data; and variances based on timing of reporting and/or if referrals are eventually canceled.

The total cost of PT CC referrals from FY 2020 to FY 2022 in selected VISNs was about $220,615,399 (Appendix 6). Appendix 7 details the methodology for determining the average standardized episode- of-care cost by VISN and how referral costs are calculated. Data show a continuous increase in total estimated cost from $46.8 million in FY 2020 to $92.1 million in FY 2022. From FY 2020 to FY 2022, aggregate costs ranged from $6,758,053 in VISN 2 to $47,209,162 in VISN 8 (Figure 3). The total referral cost for PT was highest at VISN 4 in FY 2020 ($10,447,140) and highest at VISN 22 in FY 2021 ($18,835,657) and FY 2022 ($22,962,438) (Figure 4). For referral costs from FY 2020 to FY 2022, distance accounted for $75,561,948 (34.3%), timeliness of care accounted for $60,413,496 (27.3%), and best medical interest accounted for $46,291,390 (21.0%) (Table 4).

0225FED-ePT-A70225FED-ePT-A6

 

0225FED-ePT-F30225FED-ePT-F40225FED-ePT-T4

Overall costs were primarily driven by specific VISNs within each eligibility type (Appendix 8; Figure 5). VISN 19, VISN 22, and VISN 15 accounted for the highest referral costs for distance; VISN 22, VISN 8, and VISN 19 accounted for the secondhighest referral cost, timeliness of care; and VISN 4, VISN 8, and VISN 12 accounted for the third-highest referral cost, best medical interest (Figure 5). VISN 2, VISN 4, VISN 12, VISN 15, and VISN 22 had service unavailable as an eligibility type with 1 of the top 3 associated referral costs, which was higher in cost than timeliness of care for VISN 2, VISN 4, VISN 12, and VISN 15.

0225FED-ePT-A280225FED-ePT-F5

Discussion

This study examines the referral of rehabilitation PT services to CC, evaluates CC costs for PT services, and analyzes utilization and cost trends among veterans within the VHA. Utilization data demonstrated a decrease in referrals from FY 2019 to FY 2020 and increases in referrals from FY 2020 to FY 2022 for most variables of interest, with cost data exhibiting similar trends. Results highlight the need for further investigation to address variations in PT referrals and costs across VISNs and eligibility reasons for CC referral.

Results demonstrated a noteworthy increase in PT CC referrals over time. The largest increase occurred from FY 2020 to FY 2021, with a smaller increase from FY 2021 to FY 2022. During this period, total enrollee numbers decreased by 3.0% across the 7 VISNs included in this analysis and by 1.6% across all VISNs, a trend that illustrates an overall decrease in enrollees as CC use increased. Results align with the implementation of the MISSION Act of 2018, which further expanded veterans’ options to use CC.1,6,7 Results also align with the onset of the COVID-19 pandemic, which disrupted care access for many veterans, placed a larger emphasis on the use of telehealth, and increased opportunities to stay within the VA for care by rapidly shifting to telehealth and leveraging telerehabilitation investments and initiatives (such as TR-EWI).20,31

VISN 8, VISN 19, and VISN 22, accounted for more than half of PT referrals. These VISNs had higher enrollee counts compared to the other VISNs.32 VISN 8 consistently had high levels of referrals, whereas VISN 19 and VISN 22 saw dramatic increases in FY 2021 and FY 2022. In contrast, VISN 4 and VISN 12 gradually decreased referrals during the study. VISN 2 had the lowest referral numbers during the study period, and all stations with the lowest individual referral numbers were located within VISN 2. Of the VISNs included in this study, VISN 2 had the second lowest number of enrollees (324,042).32 Reasons for increases and decreases over time could not be determined based on data collected in this study.

There were more urban than rural PT CC referrals; however, both exhibited an increase in referrals over time. This is consistent with population trends showing that most VHA patients (62.6%) and veterans (75.9%) reside in urban areas, which could explain some of the trends in this study.33 Some VISNs have larger urban catchment areas (eg, VISN 8 and VISN 22), and some have larger rural catchment areas (eg, VISN 15 and VISN 19), which could partially explain the rural-urban differences by VISN.32 Rural-urban referral trends might also reflect existing health care delivery system deficits in rural areas and known challenges associated with accessing health care for veterans living in rural communities.8,9

This study found larger differences in rural and urban PT CC referrals for younger age groups, with more than twice as many urban referrals in veterans aged 20 to 29 years and aged 30 to 39 years, and roughly 1.8 times as many urban referrals in veterans aged 40 to 49 years. However, there were similar numbers of rural and urban referrals in those aged 70 to 79 years and aged 80 to 89 years. These trends are consistent with data showing veterans residing in rural communities are older than their urban counterparts.23,34 Data suggest that older veteran populations might seek PT at higher rates than younger veteran populations. Moreover, data suggest there could be differences in PT-seeking rates for younger veteran populations who reside in rural vs urban areas. Additional research is needed to understand these trends.

Distance and timeliness of care were the predominant reasons for referral among eligibility groups, which is consistent with the MISSION Act goals.1,6,7 The most common eligibility reason for rural referrals was distance; timeliness of care was most common for urban referrals. This finding is expected, as veterans living in rural communities are farther away from VHA facilities and have longer drive times, whereas veterans living in urban communities might live closer, yet experience longer wait times due to services and/or appointment availability. Best medical interest accounted for almost 20% of referrals, which does not provide detailed insights into why those veterans were referred to CC.

The top PT diagnoses referred to CC were related to bone, joint, or soft tissue disorders of the lower back, shoulder, and knee. This suggests that musculoskeletal-related issues are prevalent among veterans seeking PT care, which is consistent with research that found > 50% of veterans receiving VHA care have musculoskeletal disorders.35 The probability of experiencing musculoskeletal problems increases with age, as does the need for PT services. Amputations and fractures accounted for < 1% of CC referrals, which is consistent with the historic provision of VHA clinical specialized care to conditions prevalent among veterans. It may also represent VHA efforts to internally provide care for complex conditions requiring more extensive interdisciplinary coordination.

The total cost of referrals over time was about $221 million. VISN 8 accounted for the highest overall cost; VISN 2 had the lowest, mirroring referral utilization trends and aligning with VISN enrollee numbers. VISN 19 and VISN 22 reported large cost increases from FY 2020 to FY 2021. Total referral costs increased by $34.9 million from FY 2020 to FY 2021, which may be due to health care inflation (2.9% during FY 2019 to FY 2022), increased awareness of CC services, or increased VHA wait times.36 Additionally, there were limitations in care provided across health care systems during the COVID-19 pandemic, including the VA.5 The increase from FY 2020 to FY 2021 may reflect a rebound from restrictions in appointments across VA, CC, and the private sector.

While the increase in total referral cost may be partly attributed to inflation, the cost effectiveness and efficiency of referring veterans to CC vs keeping veterans within VHA care is an ongoing debate.5 Examining and addressing cost drivers within the top eligibility types and their respective VISNs is necessary to determine resource allocation and improve quality of care. This study found that best medical interest and unavailable services accounted for 33.4% of the total cost of CC referrals, highlighting the need for policies that strengthen in-house competencies and recruit personnel to provide PT services currently unavailable within the VA.

Future Directions

The VHA should explore opportunities for in-house care, especially for services appropriate for telehealth.18,20,37 Data indicated a smaller cost increase from FY 2021 to FY 2022 compared to the relatively large increase from FY 2020 to FY 2021. The increased telehealth usage across VHA by TR-EWI and non—TR-EWI sites within selected VISNs may have contributed to limiting the increase in CC costs. Future studies should investigate contextual factors of increased telehealth usage, which would offer guidance for implementation to optimize the integration of telehealth with PT rehabilitation provided in-house. Additionally, future studies can examine potential limitations experienced during PT telehealth visits, such as the inability to conduct hands-on assessments, challenges in viewing the quality of patient movement, ensuring patient safety in the remote environment, and the lack of PT equipment in homes for telehealth visits, and how these challenges are being addressed.38,39 Research is also needed to understand tradeoffs of CC vs VHA care and the potential and cost benefits of keeping veterans within VHA using programs like TR-EWI.5 Veterans living in rural communities may especially benefit from this as expanding telehealth options can provide access to PT care that may not be readily available, enabling them to stay connected and engaged in their care.18,40

Future studies could examine contributory factors to rising costs, such as demographic shifts, changes in PT service utilization, and policy. Researchers might also consider qualitative studies with clinicians and veterans within each VISN, which may provide insights into how local factors impact PT referral to the community.

Limitations

Due to its descriptive nature, this study can only speculate about factors influencing trends. Limitations include the inability to link the Palantir and CC Dashboard datasets for cost comparisons and potential data change over time on Palantir due to platform updates. The focus on VISNs with TREWI sites limited generalizability and this study did not compare CC PT vs VHA PT. Finally, there may have been cost drivers not identified in this study.

Conclusions

This descriptive study provides insights into the utilization and cost of PT CC referrals for selected VISNs. Cost trends underscore the financial commitment to providing PT services to veterans. Understanding what factors are driving this cost is necessary for VHA to optimally provide and manage the rehabilitation resources needed to serve veterans through traditional in-person care, telehealth, and CC options while ensuring timely, highquality care.

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Correspondence: Kelsea LeBeau ([email protected])

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Author disclosures: The authors report no actual or potential conflicts of interest concerning this article.

Correspondence: Kelsea LeBeau ([email protected])

Fed Pract. 2025;42(2). Published online February 18. doi:10.12788/fp.0556

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Author affiliations:
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bMississippi State University, Starkville
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Author disclosures: The authors report no actual or potential conflicts of interest concerning this article.

Correspondence: Kelsea LeBeau ([email protected])

Fed Pract. 2025;42(2). Published online February 18. doi:10.12788/fp.0556

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The Veterans Health Administration (VHA) is the largest US integrated health system, providing care to veterans through VHA and non-VHA practitioners and facilities.1,2 Providing high-quality, timely, and veteran-centric care remains a priority for the VHA. Legislative efforts have expanded opportunities for eligible veterans to receive care in the community purchased by VHA, known as community care (CC).1 The Veterans Access, Choice, and Accountability Act of 2014 came in response to reports of long wait times and drive times for patients.3-5 The MISSION Act of 2018 expanded access to CC by streamlining it and broadening eligibility criteria, especially for veterans in rural communities who often experience more barriers in accessing care than veterans living in urban communities.1,6-10 Since the implementation of the Choice and MISSION Acts, > 2.7 million veterans have received care through community practitioners within the VHA CC network.11

Background

Increased access to CC could benefit veterans living in rural communities by increasing care options and circumventing challenges to accessing VHA care (ie, geographic, transportation, and distance barriers, practitioner and specialist shortages, and hospital closures). 5,9,10,12,13 However, health care system deficits in rural areas could also limit CC effectiveness for veterans living in those communities. 3 Other challenges posed by using CC include care coordination, information sharing, care continuity, delayed payments to CC practitioners, and mixed findings regarding CC quality.5,8,13,14 VHA practitioners are specifically trained to meet the multifaceted needs unique to veterans’ health and subculture, training CC practitioners may not receive.5,15

CC offers services for primary care and a broad range of specialties, including rehabilitation services such as physical therapy (PT).6 PT is used for the effective treatment of various conditions veterans experience and promote wellbeing and independence.16 US Department of Veterans Affairs (VA) databases reveal a high prevalence of veterans receiving PT services through CC; PT is one of the most frequently used CC outpatient specialty services by veterans living in rural communities.14,17

Telerehabitltation Enterprisewide Initiative

VHA has greatly invested in delivering care virtually, especially for veterans living in rural communities.18 In 2017, the VHA Office of Rural Health funded the Telerehabilitation Enterprise-Wide Initiative (TR-EWI) in partnership with the Physical Medicine and Rehabilitation Services national program office to increase access to specialized rehabilitation services for veterans living in rural communities by leveraging telehealth technologies.18-21 This alternative mode of health care delivery allows clinicians to overcome access barriers by delivering rehabilitation therapies directly to veterans' homes or nearby community-based outpatient clinics. TR-EWI was conceived as a hub-and-spoke model, where rehabilitation expertise at the hub was virtually delivered to spoke sites that did not have in-house expertise. In subsequent years, the TR-EWI also evolved to provide targeted telerehabilitation programs within rural-serving community-based outpatient clinics, including PT as a predominant service.19,20

As TR-EWI progressed—and in conjunction with the uptake of telehealth across VHA during the COVID-19 pandemic—there has been increased focus on PT telerehabilitation, especially for the 4.6 million veterans in rural communities.18,22,23 Because health care delivery system deficits in rural areas could limit the effective use of CC, many TR-EWI sites hope to reduce their CC referrals by providing telehealth PT services to veterans who might otherwise need to be referred to CC. This strategy aligns with VHA goals of providing high-quality and timely care. To better understand opportunities for programs like TR-EWI to provide rehabilitation services for veterans and reduce care sent to the community, research that examines CC referral trends for PT over time is warranted.

This study examines CC from a rehabilitation perspective with a focus on CC referral trends for PT, specifically for Veterans Integrated Service Networks (VISNs) where TREWI sites are located. The study’s objectives were to describe rehabilitation PT services being referred to CC and examine associated CC costs for PT services. Two research questions guided the study. First, what are the utilization trends for CC PT referrals from fiscal year (FY) 2019 to FY 2022? Secondly, what is the cost breakdown of CC for PT referrals from FY 2020 to FY 2022?

Methods

This study was conducted by a multidisciplinary team comprised of public health, disability, rehabilitation counseling, and PT professionals. It was deemed a quality improvement project under VA guidance and followed the SQUIRE guidelines for quality improvement reporting.24,25 The study used the VA Common Operating Platform (Palantir) to obtain individual-level CC referral data from the HealthShare Referral Manager (HSRM) database and consult data from the Computerized Patient Record System. Palantir is used to store and integrate VA data derived from the VA Corporate Data Warehouse and VHA Support Service Center. Referrals are authorizations for care to be delivered by a CC practitioner.

TR-EWI is comprised of 7 sites: VISN 2, VISN 4, VISN 8, VISN 12, VISN 15, VISN 19, and VISN 22. Each site provides telerehabilitation services with an emphasis on reaching veterans living in rural communities. We joined the referrals and consults cubes in Palantir to extract PT referrals for FY 2019 to FY 2022 for the 7 VISNs with TR-EWI sites and obtain referral-specific information and demographic characteristics. 26 Data were extracted in October 2022.

The VHA Community Care Referral Dashboard (CC Dashboard) provided nonindividual level CC cost data.27 The CC Dashboard provides insights into the costs of CC services for VHA enrollees by category of care, standardized episode of care, and eligibility. Data are based on nationallevel HSRM referrals that are not suspended or linked to a canceled or discontinued consult. Data were aggregated by VISN. The dashboard only includes referrals dating back to FY 2020; therefore, PT data from FY 2020 through FY 2022 for VISNs with TR-EWI sites were collected. Data were extracted in December 2022.

This study examined CC referrals, station name, eligibility types, clinical diagnoses (International Classification of Diseases, Tenth Revision codes), and demographic information in the Palantir dataset. Six eligibility criteria can qualify a veteran to receive CC.28 Within clinical diagnoses, the variable of interest was the provisional diagnosis. Patient demographics included age, gender, and rurality of residence, as determined by the Rural-Urban Commuting Area system.29,30 Rural and highly rural categories were combined for analysis. For the CC cost dataset, this study examined CC referrals, referral cost, and eligibility type.

Analysis

For the first research question, we examined referral data from FY 2019 to FY 2022 using the Palantir dataset, performed descriptive statistical analysis for all variables, and analyzed data to identify trends. Descriptive statistics were completed using IBM SPSS Statistics for Windows Version 29.0.0.0.

A qualitative analysis of provisional diagnosis data revealed what is being referred to CC for PT. A preliminary overview of provisional diagnosis data was conducted to familiarize coders with the data. We developed a coding framework to categorize diagnoses based on anatomical location, body structure, and clinical areas of interest. Data were reviewed individually and grouped into categories within the coding framework before meeting as a team to achieve group consensus on categorization. We then totaled the frequency of occurrence for provisional diagnoses within each category. Qualitative analyses were completed using Microsoft Excel.

For the second research question, the study used the CC cost dataset to examine the cost breakdown of CC PT referrals from FY 2020 to FY 2022. We calculated the number and cost of PT referrals across eligibility groups for each FY and VISN. Data were analyzed using SPSS to identify cost trends.

Results

There were 344,406 referrals to CC for PT from FY 2019 to FY 2022 for the 7 VISNs analyzed (Table 1). Of these, 22.5% were from FY 2019, 19.1% from FY 2020, 28.2% from FY 2021, and 30.3% from FY 2022. VISN 8 and VISN 22 reported the most overall PT referrals, with VISN 8 comprising 22.2% and VISN 22 comprising 18.1% of all referrals. VISN 2 reported the least overall referrals (3.7%). VISN 4 and VISN 12 had decreases in referrals over time. VISN 2 and VISN 15 had decreases in referrals from FY 2019 to FY 2021 and slight increases from FY 2021 to FY 2022. VISN 19 and VISN 22 both saw slight increases from FY 2019 to FY 2020 and substantial increases from FY 2020 to FY 2022, with FY 2022 accounting for 40.0% and 42.3% of all referrals for VISN 19 and VISN 20, respectively (Figure 1).

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For FY 2019 and FY 2020, VISN 8 had the highest percentage of referrals (26.7% and 23.2%, respectively), whereas VISN 22 was among the lowest (7.3% and 11.4%, respectively). However, for FY 2021 and FY 2022, VISN 22 reported the highest percentage of referrals (23.5% and 25.3%, respectively) compared to all other VISNs. VISN 2 consistently reported the lowest percentage of referrals across all years.

There were 56 stations analyzed across the 7 VISNs (Appendix 1). Nine stations each accounted for ≥ 3.0% of the total PT referrals and only 2 stations accounted for > 5.0% of referrals. Orlando, Florida (6.0%), Philadelphia, Pennsylvania (5.2%), Tampa, Florida (4.9%), Aurora, Colorado (4.9%), and Gainesville, Florida (4.4%) reported the top 5 highest referrals, with 3 being from VISN 8 (Orlando, Tampa, Gainesville). Stations with the lowest reported referrals were all in VISN 2 in New York: The Bronx, (0%), New York Harbor (0%), Hudson Valley (0.1%) and Finger Lakes (0.2%).

0225FED-ePT-A1
Rurality

Urban stations comprised 56.2% and rural stations comprised 39.8% of PT CC referrals, while 0.2% of referrals were from insular isle US territories: Guam, American Samoa, Northern Marianas, and the Virgin Islands. The sample had missing or unknown data for 3.8% of referrals. FY 2022 had the largest difference in rural and urban referrals. Additionally, there was an overall trend of more referrals over time for rural and urban, with a large increase in rural (+40.0%) and urban (+62.7%) referrals from FY 2020 to FY 2021 and a modest increase from FY 2021 to FY 2022 (+5.2% for rural and +9.1% for urban). There was a decrease in rural (-7.0%) and urban (-3.5%) referrals from FY 2019 to FY 2020 (Figure 2).

0225FED-ePT-F2

There were differences in referrals by rurality and VISN (Table 2). VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals, whereas VISN 4, VISN 8, and VISN 22 reported more urban than rural referrals. VISN 2 reported similar numbers for both, with slightly more urban than rural referrals. When reviewing trends over time for each FY, VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals and VISN 4, VISN 8, and VISN 22 had more urban than rural referrals. In FY 2019 and FY 2020, VISN 2 reported slightly more urban than rural referrals but almost the same number of referrals in FY 2021 and FY 2022 (Appendix 2).

0225FED-ePT-T20225FED-ePT-A2
Demographics

The mean (SD) age was 61.2 (15.8) years (range, 20-105). Most PT CC referrals were for veterans aged 70 to 79 years (26.9%), followed by 60 to 69 years (20.7%), and 50 to 59 years (16.4%) (Appendix 3). Trends were consistent across VISNs. There was less of a difference between rural and urban referral percentages as the population aged. Veterans aged < 49 years residing in more urban areas accounted for more referrals to CC compared to their rural counterparts. This difference was less apparent in the 70 to 79 years and 80 to 89 years age brackets.

0225FED-ePT-A3

Most PT CC referrals (81.2%) were male and 14.8% were female. About 3.6% of referral data were missing sex information, and there was a smaller difference between male veterans living in rural communities and male veterans living in urban communities compared with female veterans. A total of 42.9% of male veterans resided in rural areas compared to 56.8% in urban areas; 32.7% of female veterans resided in rural areas compared to 66.9% in urban areas (Appendix 3).

Other Criteria

Of the 334,406 referrals, 114,983 (34.4%) had eligibility data, mostly from FY 2021 and FY 2022 (Table 3). Available eligibility data were likely affected by the MISSION Act and new regulations for reporting CC eligibility. Distance (33.4%) was the most common eligibility criteria, followed by timeliness of care (28.8%), and best medical interest (19.8%); 40.4% were rural and 59.5% were urban. Distance (55.4%) was most common for rural veterans, while timeliness of care (39.7%) was most common for urban veterans. For both groups, the second most common eligibility reason was best medical interest (Appendix 4).

0225FED-ePT-T30225FED-ePT-A4

Bone, joint, or soft tissue disorders were common diagnoses, with 25.2% located in the lower back, 14.7% in the shoulder, and 12.8% in the knee (Appendix 5). Amputations of the upper and lower limbs, fractures, cancer-related diagnoses, integumentary system disorders, thoracic and abdominal injuries and disorders, and other medical and mental health conditions each accounted for < 1% of the total diagnoses.

0225FED-ePT-A5
Costs

At time of analysis, the CC Dashboard had cost data available for 200,204 CC PT referrals from FY 2020 to FY 2022. The difference in referral numbers for the 2 datasets is likely attributed to several factors: CC cost data is exclusively from the HSRM, whereas Palantir includes other data sources; how VA cleans data pulled into Palantir; how the CC Dashboard algorithm populates data; and variances based on timing of reporting and/or if referrals are eventually canceled.

The total cost of PT CC referrals from FY 2020 to FY 2022 in selected VISNs was about $220,615,399 (Appendix 6). Appendix 7 details the methodology for determining the average standardized episode- of-care cost by VISN and how referral costs are calculated. Data show a continuous increase in total estimated cost from $46.8 million in FY 2020 to $92.1 million in FY 2022. From FY 2020 to FY 2022, aggregate costs ranged from $6,758,053 in VISN 2 to $47,209,162 in VISN 8 (Figure 3). The total referral cost for PT was highest at VISN 4 in FY 2020 ($10,447,140) and highest at VISN 22 in FY 2021 ($18,835,657) and FY 2022 ($22,962,438) (Figure 4). For referral costs from FY 2020 to FY 2022, distance accounted for $75,561,948 (34.3%), timeliness of care accounted for $60,413,496 (27.3%), and best medical interest accounted for $46,291,390 (21.0%) (Table 4).

0225FED-ePT-A70225FED-ePT-A6

 

0225FED-ePT-F30225FED-ePT-F40225FED-ePT-T4

Overall costs were primarily driven by specific VISNs within each eligibility type (Appendix 8; Figure 5). VISN 19, VISN 22, and VISN 15 accounted for the highest referral costs for distance; VISN 22, VISN 8, and VISN 19 accounted for the secondhighest referral cost, timeliness of care; and VISN 4, VISN 8, and VISN 12 accounted for the third-highest referral cost, best medical interest (Figure 5). VISN 2, VISN 4, VISN 12, VISN 15, and VISN 22 had service unavailable as an eligibility type with 1 of the top 3 associated referral costs, which was higher in cost than timeliness of care for VISN 2, VISN 4, VISN 12, and VISN 15.

0225FED-ePT-A280225FED-ePT-F5

Discussion

This study examines the referral of rehabilitation PT services to CC, evaluates CC costs for PT services, and analyzes utilization and cost trends among veterans within the VHA. Utilization data demonstrated a decrease in referrals from FY 2019 to FY 2020 and increases in referrals from FY 2020 to FY 2022 for most variables of interest, with cost data exhibiting similar trends. Results highlight the need for further investigation to address variations in PT referrals and costs across VISNs and eligibility reasons for CC referral.

Results demonstrated a noteworthy increase in PT CC referrals over time. The largest increase occurred from FY 2020 to FY 2021, with a smaller increase from FY 2021 to FY 2022. During this period, total enrollee numbers decreased by 3.0% across the 7 VISNs included in this analysis and by 1.6% across all VISNs, a trend that illustrates an overall decrease in enrollees as CC use increased. Results align with the implementation of the MISSION Act of 2018, which further expanded veterans’ options to use CC.1,6,7 Results also align with the onset of the COVID-19 pandemic, which disrupted care access for many veterans, placed a larger emphasis on the use of telehealth, and increased opportunities to stay within the VA for care by rapidly shifting to telehealth and leveraging telerehabilitation investments and initiatives (such as TR-EWI).20,31

VISN 8, VISN 19, and VISN 22, accounted for more than half of PT referrals. These VISNs had higher enrollee counts compared to the other VISNs.32 VISN 8 consistently had high levels of referrals, whereas VISN 19 and VISN 22 saw dramatic increases in FY 2021 and FY 2022. In contrast, VISN 4 and VISN 12 gradually decreased referrals during the study. VISN 2 had the lowest referral numbers during the study period, and all stations with the lowest individual referral numbers were located within VISN 2. Of the VISNs included in this study, VISN 2 had the second lowest number of enrollees (324,042).32 Reasons for increases and decreases over time could not be determined based on data collected in this study.

There were more urban than rural PT CC referrals; however, both exhibited an increase in referrals over time. This is consistent with population trends showing that most VHA patients (62.6%) and veterans (75.9%) reside in urban areas, which could explain some of the trends in this study.33 Some VISNs have larger urban catchment areas (eg, VISN 8 and VISN 22), and some have larger rural catchment areas (eg, VISN 15 and VISN 19), which could partially explain the rural-urban differences by VISN.32 Rural-urban referral trends might also reflect existing health care delivery system deficits in rural areas and known challenges associated with accessing health care for veterans living in rural communities.8,9

This study found larger differences in rural and urban PT CC referrals for younger age groups, with more than twice as many urban referrals in veterans aged 20 to 29 years and aged 30 to 39 years, and roughly 1.8 times as many urban referrals in veterans aged 40 to 49 years. However, there were similar numbers of rural and urban referrals in those aged 70 to 79 years and aged 80 to 89 years. These trends are consistent with data showing veterans residing in rural communities are older than their urban counterparts.23,34 Data suggest that older veteran populations might seek PT at higher rates than younger veteran populations. Moreover, data suggest there could be differences in PT-seeking rates for younger veteran populations who reside in rural vs urban areas. Additional research is needed to understand these trends.

Distance and timeliness of care were the predominant reasons for referral among eligibility groups, which is consistent with the MISSION Act goals.1,6,7 The most common eligibility reason for rural referrals was distance; timeliness of care was most common for urban referrals. This finding is expected, as veterans living in rural communities are farther away from VHA facilities and have longer drive times, whereas veterans living in urban communities might live closer, yet experience longer wait times due to services and/or appointment availability. Best medical interest accounted for almost 20% of referrals, which does not provide detailed insights into why those veterans were referred to CC.

The top PT diagnoses referred to CC were related to bone, joint, or soft tissue disorders of the lower back, shoulder, and knee. This suggests that musculoskeletal-related issues are prevalent among veterans seeking PT care, which is consistent with research that found > 50% of veterans receiving VHA care have musculoskeletal disorders.35 The probability of experiencing musculoskeletal problems increases with age, as does the need for PT services. Amputations and fractures accounted for < 1% of CC referrals, which is consistent with the historic provision of VHA clinical specialized care to conditions prevalent among veterans. It may also represent VHA efforts to internally provide care for complex conditions requiring more extensive interdisciplinary coordination.

The total cost of referrals over time was about $221 million. VISN 8 accounted for the highest overall cost; VISN 2 had the lowest, mirroring referral utilization trends and aligning with VISN enrollee numbers. VISN 19 and VISN 22 reported large cost increases from FY 2020 to FY 2021. Total referral costs increased by $34.9 million from FY 2020 to FY 2021, which may be due to health care inflation (2.9% during FY 2019 to FY 2022), increased awareness of CC services, or increased VHA wait times.36 Additionally, there were limitations in care provided across health care systems during the COVID-19 pandemic, including the VA.5 The increase from FY 2020 to FY 2021 may reflect a rebound from restrictions in appointments across VA, CC, and the private sector.

While the increase in total referral cost may be partly attributed to inflation, the cost effectiveness and efficiency of referring veterans to CC vs keeping veterans within VHA care is an ongoing debate.5 Examining and addressing cost drivers within the top eligibility types and their respective VISNs is necessary to determine resource allocation and improve quality of care. This study found that best medical interest and unavailable services accounted for 33.4% of the total cost of CC referrals, highlighting the need for policies that strengthen in-house competencies and recruit personnel to provide PT services currently unavailable within the VA.

Future Directions

The VHA should explore opportunities for in-house care, especially for services appropriate for telehealth.18,20,37 Data indicated a smaller cost increase from FY 2021 to FY 2022 compared to the relatively large increase from FY 2020 to FY 2021. The increased telehealth usage across VHA by TR-EWI and non—TR-EWI sites within selected VISNs may have contributed to limiting the increase in CC costs. Future studies should investigate contextual factors of increased telehealth usage, which would offer guidance for implementation to optimize the integration of telehealth with PT rehabilitation provided in-house. Additionally, future studies can examine potential limitations experienced during PT telehealth visits, such as the inability to conduct hands-on assessments, challenges in viewing the quality of patient movement, ensuring patient safety in the remote environment, and the lack of PT equipment in homes for telehealth visits, and how these challenges are being addressed.38,39 Research is also needed to understand tradeoffs of CC vs VHA care and the potential and cost benefits of keeping veterans within VHA using programs like TR-EWI.5 Veterans living in rural communities may especially benefit from this as expanding telehealth options can provide access to PT care that may not be readily available, enabling them to stay connected and engaged in their care.18,40

Future studies could examine contributory factors to rising costs, such as demographic shifts, changes in PT service utilization, and policy. Researchers might also consider qualitative studies with clinicians and veterans within each VISN, which may provide insights into how local factors impact PT referral to the community.

Limitations

Due to its descriptive nature, this study can only speculate about factors influencing trends. Limitations include the inability to link the Palantir and CC Dashboard datasets for cost comparisons and potential data change over time on Palantir due to platform updates. The focus on VISNs with TREWI sites limited generalizability and this study did not compare CC PT vs VHA PT. Finally, there may have been cost drivers not identified in this study.

Conclusions

This descriptive study provides insights into the utilization and cost of PT CC referrals for selected VISNs. Cost trends underscore the financial commitment to providing PT services to veterans. Understanding what factors are driving this cost is necessary for VHA to optimally provide and manage the rehabilitation resources needed to serve veterans through traditional in-person care, telehealth, and CC options while ensuring timely, highquality care.

 

The Veterans Health Administration (VHA) is the largest US integrated health system, providing care to veterans through VHA and non-VHA practitioners and facilities.1,2 Providing high-quality, timely, and veteran-centric care remains a priority for the VHA. Legislative efforts have expanded opportunities for eligible veterans to receive care in the community purchased by VHA, known as community care (CC).1 The Veterans Access, Choice, and Accountability Act of 2014 came in response to reports of long wait times and drive times for patients.3-5 The MISSION Act of 2018 expanded access to CC by streamlining it and broadening eligibility criteria, especially for veterans in rural communities who often experience more barriers in accessing care than veterans living in urban communities.1,6-10 Since the implementation of the Choice and MISSION Acts, > 2.7 million veterans have received care through community practitioners within the VHA CC network.11

Background

Increased access to CC could benefit veterans living in rural communities by increasing care options and circumventing challenges to accessing VHA care (ie, geographic, transportation, and distance barriers, practitioner and specialist shortages, and hospital closures). 5,9,10,12,13 However, health care system deficits in rural areas could also limit CC effectiveness for veterans living in those communities. 3 Other challenges posed by using CC include care coordination, information sharing, care continuity, delayed payments to CC practitioners, and mixed findings regarding CC quality.5,8,13,14 VHA practitioners are specifically trained to meet the multifaceted needs unique to veterans’ health and subculture, training CC practitioners may not receive.5,15

CC offers services for primary care and a broad range of specialties, including rehabilitation services such as physical therapy (PT).6 PT is used for the effective treatment of various conditions veterans experience and promote wellbeing and independence.16 US Department of Veterans Affairs (VA) databases reveal a high prevalence of veterans receiving PT services through CC; PT is one of the most frequently used CC outpatient specialty services by veterans living in rural communities.14,17

Telerehabitltation Enterprisewide Initiative

VHA has greatly invested in delivering care virtually, especially for veterans living in rural communities.18 In 2017, the VHA Office of Rural Health funded the Telerehabilitation Enterprise-Wide Initiative (TR-EWI) in partnership with the Physical Medicine and Rehabilitation Services national program office to increase access to specialized rehabilitation services for veterans living in rural communities by leveraging telehealth technologies.18-21 This alternative mode of health care delivery allows clinicians to overcome access barriers by delivering rehabilitation therapies directly to veterans' homes or nearby community-based outpatient clinics. TR-EWI was conceived as a hub-and-spoke model, where rehabilitation expertise at the hub was virtually delivered to spoke sites that did not have in-house expertise. In subsequent years, the TR-EWI also evolved to provide targeted telerehabilitation programs within rural-serving community-based outpatient clinics, including PT as a predominant service.19,20

As TR-EWI progressed—and in conjunction with the uptake of telehealth across VHA during the COVID-19 pandemic—there has been increased focus on PT telerehabilitation, especially for the 4.6 million veterans in rural communities.18,22,23 Because health care delivery system deficits in rural areas could limit the effective use of CC, many TR-EWI sites hope to reduce their CC referrals by providing telehealth PT services to veterans who might otherwise need to be referred to CC. This strategy aligns with VHA goals of providing high-quality and timely care. To better understand opportunities for programs like TR-EWI to provide rehabilitation services for veterans and reduce care sent to the community, research that examines CC referral trends for PT over time is warranted.

This study examines CC from a rehabilitation perspective with a focus on CC referral trends for PT, specifically for Veterans Integrated Service Networks (VISNs) where TREWI sites are located. The study’s objectives were to describe rehabilitation PT services being referred to CC and examine associated CC costs for PT services. Two research questions guided the study. First, what are the utilization trends for CC PT referrals from fiscal year (FY) 2019 to FY 2022? Secondly, what is the cost breakdown of CC for PT referrals from FY 2020 to FY 2022?

Methods

This study was conducted by a multidisciplinary team comprised of public health, disability, rehabilitation counseling, and PT professionals. It was deemed a quality improvement project under VA guidance and followed the SQUIRE guidelines for quality improvement reporting.24,25 The study used the VA Common Operating Platform (Palantir) to obtain individual-level CC referral data from the HealthShare Referral Manager (HSRM) database and consult data from the Computerized Patient Record System. Palantir is used to store and integrate VA data derived from the VA Corporate Data Warehouse and VHA Support Service Center. Referrals are authorizations for care to be delivered by a CC practitioner.

TR-EWI is comprised of 7 sites: VISN 2, VISN 4, VISN 8, VISN 12, VISN 15, VISN 19, and VISN 22. Each site provides telerehabilitation services with an emphasis on reaching veterans living in rural communities. We joined the referrals and consults cubes in Palantir to extract PT referrals for FY 2019 to FY 2022 for the 7 VISNs with TR-EWI sites and obtain referral-specific information and demographic characteristics. 26 Data were extracted in October 2022.

The VHA Community Care Referral Dashboard (CC Dashboard) provided nonindividual level CC cost data.27 The CC Dashboard provides insights into the costs of CC services for VHA enrollees by category of care, standardized episode of care, and eligibility. Data are based on nationallevel HSRM referrals that are not suspended or linked to a canceled or discontinued consult. Data were aggregated by VISN. The dashboard only includes referrals dating back to FY 2020; therefore, PT data from FY 2020 through FY 2022 for VISNs with TR-EWI sites were collected. Data were extracted in December 2022.

This study examined CC referrals, station name, eligibility types, clinical diagnoses (International Classification of Diseases, Tenth Revision codes), and demographic information in the Palantir dataset. Six eligibility criteria can qualify a veteran to receive CC.28 Within clinical diagnoses, the variable of interest was the provisional diagnosis. Patient demographics included age, gender, and rurality of residence, as determined by the Rural-Urban Commuting Area system.29,30 Rural and highly rural categories were combined for analysis. For the CC cost dataset, this study examined CC referrals, referral cost, and eligibility type.

Analysis

For the first research question, we examined referral data from FY 2019 to FY 2022 using the Palantir dataset, performed descriptive statistical analysis for all variables, and analyzed data to identify trends. Descriptive statistics were completed using IBM SPSS Statistics for Windows Version 29.0.0.0.

A qualitative analysis of provisional diagnosis data revealed what is being referred to CC for PT. A preliminary overview of provisional diagnosis data was conducted to familiarize coders with the data. We developed a coding framework to categorize diagnoses based on anatomical location, body structure, and clinical areas of interest. Data were reviewed individually and grouped into categories within the coding framework before meeting as a team to achieve group consensus on categorization. We then totaled the frequency of occurrence for provisional diagnoses within each category. Qualitative analyses were completed using Microsoft Excel.

For the second research question, the study used the CC cost dataset to examine the cost breakdown of CC PT referrals from FY 2020 to FY 2022. We calculated the number and cost of PT referrals across eligibility groups for each FY and VISN. Data were analyzed using SPSS to identify cost trends.

Results

There were 344,406 referrals to CC for PT from FY 2019 to FY 2022 for the 7 VISNs analyzed (Table 1). Of these, 22.5% were from FY 2019, 19.1% from FY 2020, 28.2% from FY 2021, and 30.3% from FY 2022. VISN 8 and VISN 22 reported the most overall PT referrals, with VISN 8 comprising 22.2% and VISN 22 comprising 18.1% of all referrals. VISN 2 reported the least overall referrals (3.7%). VISN 4 and VISN 12 had decreases in referrals over time. VISN 2 and VISN 15 had decreases in referrals from FY 2019 to FY 2021 and slight increases from FY 2021 to FY 2022. VISN 19 and VISN 22 both saw slight increases from FY 2019 to FY 2020 and substantial increases from FY 2020 to FY 2022, with FY 2022 accounting for 40.0% and 42.3% of all referrals for VISN 19 and VISN 20, respectively (Figure 1).

0225FED-ePT-T10225FED-ePT-F1

For FY 2019 and FY 2020, VISN 8 had the highest percentage of referrals (26.7% and 23.2%, respectively), whereas VISN 22 was among the lowest (7.3% and 11.4%, respectively). However, for FY 2021 and FY 2022, VISN 22 reported the highest percentage of referrals (23.5% and 25.3%, respectively) compared to all other VISNs. VISN 2 consistently reported the lowest percentage of referrals across all years.

There were 56 stations analyzed across the 7 VISNs (Appendix 1). Nine stations each accounted for ≥ 3.0% of the total PT referrals and only 2 stations accounted for > 5.0% of referrals. Orlando, Florida (6.0%), Philadelphia, Pennsylvania (5.2%), Tampa, Florida (4.9%), Aurora, Colorado (4.9%), and Gainesville, Florida (4.4%) reported the top 5 highest referrals, with 3 being from VISN 8 (Orlando, Tampa, Gainesville). Stations with the lowest reported referrals were all in VISN 2 in New York: The Bronx, (0%), New York Harbor (0%), Hudson Valley (0.1%) and Finger Lakes (0.2%).

0225FED-ePT-A1
Rurality

Urban stations comprised 56.2% and rural stations comprised 39.8% of PT CC referrals, while 0.2% of referrals were from insular isle US territories: Guam, American Samoa, Northern Marianas, and the Virgin Islands. The sample had missing or unknown data for 3.8% of referrals. FY 2022 had the largest difference in rural and urban referrals. Additionally, there was an overall trend of more referrals over time for rural and urban, with a large increase in rural (+40.0%) and urban (+62.7%) referrals from FY 2020 to FY 2021 and a modest increase from FY 2021 to FY 2022 (+5.2% for rural and +9.1% for urban). There was a decrease in rural (-7.0%) and urban (-3.5%) referrals from FY 2019 to FY 2020 (Figure 2).

0225FED-ePT-F2

There were differences in referrals by rurality and VISN (Table 2). VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals, whereas VISN 4, VISN 8, and VISN 22 reported more urban than rural referrals. VISN 2 reported similar numbers for both, with slightly more urban than rural referrals. When reviewing trends over time for each FY, VISN 12, VISN 15, and VISN 19 reported more rural than urban referrals and VISN 4, VISN 8, and VISN 22 had more urban than rural referrals. In FY 2019 and FY 2020, VISN 2 reported slightly more urban than rural referrals but almost the same number of referrals in FY 2021 and FY 2022 (Appendix 2).

0225FED-ePT-T20225FED-ePT-A2
Demographics

The mean (SD) age was 61.2 (15.8) years (range, 20-105). Most PT CC referrals were for veterans aged 70 to 79 years (26.9%), followed by 60 to 69 years (20.7%), and 50 to 59 years (16.4%) (Appendix 3). Trends were consistent across VISNs. There was less of a difference between rural and urban referral percentages as the population aged. Veterans aged < 49 years residing in more urban areas accounted for more referrals to CC compared to their rural counterparts. This difference was less apparent in the 70 to 79 years and 80 to 89 years age brackets.

0225FED-ePT-A3

Most PT CC referrals (81.2%) were male and 14.8% were female. About 3.6% of referral data were missing sex information, and there was a smaller difference between male veterans living in rural communities and male veterans living in urban communities compared with female veterans. A total of 42.9% of male veterans resided in rural areas compared to 56.8% in urban areas; 32.7% of female veterans resided in rural areas compared to 66.9% in urban areas (Appendix 3).

Other Criteria

Of the 334,406 referrals, 114,983 (34.4%) had eligibility data, mostly from FY 2021 and FY 2022 (Table 3). Available eligibility data were likely affected by the MISSION Act and new regulations for reporting CC eligibility. Distance (33.4%) was the most common eligibility criteria, followed by timeliness of care (28.8%), and best medical interest (19.8%); 40.4% were rural and 59.5% were urban. Distance (55.4%) was most common for rural veterans, while timeliness of care (39.7%) was most common for urban veterans. For both groups, the second most common eligibility reason was best medical interest (Appendix 4).

0225FED-ePT-T30225FED-ePT-A4

Bone, joint, or soft tissue disorders were common diagnoses, with 25.2% located in the lower back, 14.7% in the shoulder, and 12.8% in the knee (Appendix 5). Amputations of the upper and lower limbs, fractures, cancer-related diagnoses, integumentary system disorders, thoracic and abdominal injuries and disorders, and other medical and mental health conditions each accounted for < 1% of the total diagnoses.

0225FED-ePT-A5
Costs

At time of analysis, the CC Dashboard had cost data available for 200,204 CC PT referrals from FY 2020 to FY 2022. The difference in referral numbers for the 2 datasets is likely attributed to several factors: CC cost data is exclusively from the HSRM, whereas Palantir includes other data sources; how VA cleans data pulled into Palantir; how the CC Dashboard algorithm populates data; and variances based on timing of reporting and/or if referrals are eventually canceled.

The total cost of PT CC referrals from FY 2020 to FY 2022 in selected VISNs was about $220,615,399 (Appendix 6). Appendix 7 details the methodology for determining the average standardized episode- of-care cost by VISN and how referral costs are calculated. Data show a continuous increase in total estimated cost from $46.8 million in FY 2020 to $92.1 million in FY 2022. From FY 2020 to FY 2022, aggregate costs ranged from $6,758,053 in VISN 2 to $47,209,162 in VISN 8 (Figure 3). The total referral cost for PT was highest at VISN 4 in FY 2020 ($10,447,140) and highest at VISN 22 in FY 2021 ($18,835,657) and FY 2022 ($22,962,438) (Figure 4). For referral costs from FY 2020 to FY 2022, distance accounted for $75,561,948 (34.3%), timeliness of care accounted for $60,413,496 (27.3%), and best medical interest accounted for $46,291,390 (21.0%) (Table 4).

0225FED-ePT-A70225FED-ePT-A6

 

0225FED-ePT-F30225FED-ePT-F40225FED-ePT-T4

Overall costs were primarily driven by specific VISNs within each eligibility type (Appendix 8; Figure 5). VISN 19, VISN 22, and VISN 15 accounted for the highest referral costs for distance; VISN 22, VISN 8, and VISN 19 accounted for the secondhighest referral cost, timeliness of care; and VISN 4, VISN 8, and VISN 12 accounted for the third-highest referral cost, best medical interest (Figure 5). VISN 2, VISN 4, VISN 12, VISN 15, and VISN 22 had service unavailable as an eligibility type with 1 of the top 3 associated referral costs, which was higher in cost than timeliness of care for VISN 2, VISN 4, VISN 12, and VISN 15.

0225FED-ePT-A280225FED-ePT-F5

Discussion

This study examines the referral of rehabilitation PT services to CC, evaluates CC costs for PT services, and analyzes utilization and cost trends among veterans within the VHA. Utilization data demonstrated a decrease in referrals from FY 2019 to FY 2020 and increases in referrals from FY 2020 to FY 2022 for most variables of interest, with cost data exhibiting similar trends. Results highlight the need for further investigation to address variations in PT referrals and costs across VISNs and eligibility reasons for CC referral.

Results demonstrated a noteworthy increase in PT CC referrals over time. The largest increase occurred from FY 2020 to FY 2021, with a smaller increase from FY 2021 to FY 2022. During this period, total enrollee numbers decreased by 3.0% across the 7 VISNs included in this analysis and by 1.6% across all VISNs, a trend that illustrates an overall decrease in enrollees as CC use increased. Results align with the implementation of the MISSION Act of 2018, which further expanded veterans’ options to use CC.1,6,7 Results also align with the onset of the COVID-19 pandemic, which disrupted care access for many veterans, placed a larger emphasis on the use of telehealth, and increased opportunities to stay within the VA for care by rapidly shifting to telehealth and leveraging telerehabilitation investments and initiatives (such as TR-EWI).20,31

VISN 8, VISN 19, and VISN 22, accounted for more than half of PT referrals. These VISNs had higher enrollee counts compared to the other VISNs.32 VISN 8 consistently had high levels of referrals, whereas VISN 19 and VISN 22 saw dramatic increases in FY 2021 and FY 2022. In contrast, VISN 4 and VISN 12 gradually decreased referrals during the study. VISN 2 had the lowest referral numbers during the study period, and all stations with the lowest individual referral numbers were located within VISN 2. Of the VISNs included in this study, VISN 2 had the second lowest number of enrollees (324,042).32 Reasons for increases and decreases over time could not be determined based on data collected in this study.

There were more urban than rural PT CC referrals; however, both exhibited an increase in referrals over time. This is consistent with population trends showing that most VHA patients (62.6%) and veterans (75.9%) reside in urban areas, which could explain some of the trends in this study.33 Some VISNs have larger urban catchment areas (eg, VISN 8 and VISN 22), and some have larger rural catchment areas (eg, VISN 15 and VISN 19), which could partially explain the rural-urban differences by VISN.32 Rural-urban referral trends might also reflect existing health care delivery system deficits in rural areas and known challenges associated with accessing health care for veterans living in rural communities.8,9

This study found larger differences in rural and urban PT CC referrals for younger age groups, with more than twice as many urban referrals in veterans aged 20 to 29 years and aged 30 to 39 years, and roughly 1.8 times as many urban referrals in veterans aged 40 to 49 years. However, there were similar numbers of rural and urban referrals in those aged 70 to 79 years and aged 80 to 89 years. These trends are consistent with data showing veterans residing in rural communities are older than their urban counterparts.23,34 Data suggest that older veteran populations might seek PT at higher rates than younger veteran populations. Moreover, data suggest there could be differences in PT-seeking rates for younger veteran populations who reside in rural vs urban areas. Additional research is needed to understand these trends.

Distance and timeliness of care were the predominant reasons for referral among eligibility groups, which is consistent with the MISSION Act goals.1,6,7 The most common eligibility reason for rural referrals was distance; timeliness of care was most common for urban referrals. This finding is expected, as veterans living in rural communities are farther away from VHA facilities and have longer drive times, whereas veterans living in urban communities might live closer, yet experience longer wait times due to services and/or appointment availability. Best medical interest accounted for almost 20% of referrals, which does not provide detailed insights into why those veterans were referred to CC.

The top PT diagnoses referred to CC were related to bone, joint, or soft tissue disorders of the lower back, shoulder, and knee. This suggests that musculoskeletal-related issues are prevalent among veterans seeking PT care, which is consistent with research that found > 50% of veterans receiving VHA care have musculoskeletal disorders.35 The probability of experiencing musculoskeletal problems increases with age, as does the need for PT services. Amputations and fractures accounted for < 1% of CC referrals, which is consistent with the historic provision of VHA clinical specialized care to conditions prevalent among veterans. It may also represent VHA efforts to internally provide care for complex conditions requiring more extensive interdisciplinary coordination.

The total cost of referrals over time was about $221 million. VISN 8 accounted for the highest overall cost; VISN 2 had the lowest, mirroring referral utilization trends and aligning with VISN enrollee numbers. VISN 19 and VISN 22 reported large cost increases from FY 2020 to FY 2021. Total referral costs increased by $34.9 million from FY 2020 to FY 2021, which may be due to health care inflation (2.9% during FY 2019 to FY 2022), increased awareness of CC services, or increased VHA wait times.36 Additionally, there were limitations in care provided across health care systems during the COVID-19 pandemic, including the VA.5 The increase from FY 2020 to FY 2021 may reflect a rebound from restrictions in appointments across VA, CC, and the private sector.

While the increase in total referral cost may be partly attributed to inflation, the cost effectiveness and efficiency of referring veterans to CC vs keeping veterans within VHA care is an ongoing debate.5 Examining and addressing cost drivers within the top eligibility types and their respective VISNs is necessary to determine resource allocation and improve quality of care. This study found that best medical interest and unavailable services accounted for 33.4% of the total cost of CC referrals, highlighting the need for policies that strengthen in-house competencies and recruit personnel to provide PT services currently unavailable within the VA.

Future Directions

The VHA should explore opportunities for in-house care, especially for services appropriate for telehealth.18,20,37 Data indicated a smaller cost increase from FY 2021 to FY 2022 compared to the relatively large increase from FY 2020 to FY 2021. The increased telehealth usage across VHA by TR-EWI and non—TR-EWI sites within selected VISNs may have contributed to limiting the increase in CC costs. Future studies should investigate contextual factors of increased telehealth usage, which would offer guidance for implementation to optimize the integration of telehealth with PT rehabilitation provided in-house. Additionally, future studies can examine potential limitations experienced during PT telehealth visits, such as the inability to conduct hands-on assessments, challenges in viewing the quality of patient movement, ensuring patient safety in the remote environment, and the lack of PT equipment in homes for telehealth visits, and how these challenges are being addressed.38,39 Research is also needed to understand tradeoffs of CC vs VHA care and the potential and cost benefits of keeping veterans within VHA using programs like TR-EWI.5 Veterans living in rural communities may especially benefit from this as expanding telehealth options can provide access to PT care that may not be readily available, enabling them to stay connected and engaged in their care.18,40

Future studies could examine contributory factors to rising costs, such as demographic shifts, changes in PT service utilization, and policy. Researchers might also consider qualitative studies with clinicians and veterans within each VISN, which may provide insights into how local factors impact PT referral to the community.

Limitations

Due to its descriptive nature, this study can only speculate about factors influencing trends. Limitations include the inability to link the Palantir and CC Dashboard datasets for cost comparisons and potential data change over time on Palantir due to platform updates. The focus on VISNs with TREWI sites limited generalizability and this study did not compare CC PT vs VHA PT. Finally, there may have been cost drivers not identified in this study.

Conclusions

This descriptive study provides insights into the utilization and cost of PT CC referrals for selected VISNs. Cost trends underscore the financial commitment to providing PT services to veterans. Understanding what factors are driving this cost is necessary for VHA to optimally provide and manage the rehabilitation resources needed to serve veterans through traditional in-person care, telehealth, and CC options while ensuring timely, highquality care.

References
  1. Congressional Budget Office. The Veterans Community Care Program: Background and Early Effects. October 26, 2021. Accessed September 23, 2024. https://www.cbo.gov/publication/57257
  2. US Dept of Veterans Affairs. Providing Health Care for Veterans. Updated September 10, 2024. Accessed September 23, 2024. https://www.va.gov/health/
  3. Davila H, Rosen AK, Beilstein-Wedel E, Shwartz M, Chatelain LJ, Gurewich D. Rural veterans’ experiences with outpatient care in the Veterans Health Administration versus community care. Med Care. 2021;59(Suppl 3):S286-S291. doi:10.1097/MLR.0000000000001552
  4. Vanneman ME, Wagner TH, Shwartz M, et al. Veterans’ experiences with outpatient care: comparing the Veterans Affairs system with community-based care. Health Aff (Millwood). 2020;39(8):1368-1376. doi:10.1377/hlthaff.2019.01375
  5. Rasmussen P, Farmer CM. The promise and challenges of VA community care: veterans’ issues in focus. Rand Health Q. 2023;10(3):9.
  6. Feyman Y, Legler A, Griffith KN. Appointment wait time data for primary & specialty care in veterans health administration facilities vs. community medical centers. Data Brief. 2021;36:107134. doi:10.1016/j.dib.2021.107134
  7. Kelley AT, Greenstone CL, Kirsh SR. Defining access and the role of community care in the Veterans Health Administration. J Gen Intern Med. 2020;35(5):1584-1585. doi:10.1007/s11606-019-05358-z
  8. Garvin LA, Pugatch M, Gurewich D, Pendergast JN, Miller CJ. Interorganizational care coordination of rural veterans by Veterans Affairs and community care programs: a systematic review. Med Care. 2021;59(Suppl 3):S259-S269. doi:10.1097/MLR.0000000000001542
  9. US Dept of Veterans Affairs, Office of Rural Health. Rural Veterans: Rural Veteran Health Care Challenges. Updated May 14, 2024. Accessed September 23, 2024. https:// www.ruralhealth.va.gov/aboutus/ruralvets.asp
  10. Ohl ME, Carrell M, Thurman A, et al. “Availability of healthcare providers for rural veterans eligible for purchased care under the veterans choice act.” BMC Health Serv Res. 2018;18(1):315. doi:10.1186/s12913-018-3108-8
  11. Mattocks KM, Cunningham KJ, Greenstone C, Atkins D, Rosen AK, Upton M. Innovations in community care programs, policies, and research. Med Care. 2021;59(Suppl 3):S229-S231. doi:10.1097/MLR.0000000000001550
  12. Doyle JM, Streeter RA. Veterans’ location in health professional shortage areas: implications for access to care and workforce supply. Health Serv Res. 2017;52 Suppl 1(Suppl 1):459-480. doi:10.1111/1475-6773.12633
  13. Patzel M, Barnes C, Ramalingam N, et al. Jumping through hoops: community care clinician and staff experiences providing primary care to rural veterans. J Gen Intern Med. 2023;38(Suppl 3):821-828. doi:10.1007/s11606-023-08126-2
  14. Mattocks KM, Kroll-Desrosiers A, Kinney R, Elwy AR, Cunningham KJ, Mengeling MA. Understanding VA’s use of and relationships with community care providers under the MISSION Act. Med Care. 2021;59(Suppl 3):S252-S258. doi:10.1097/MLR.0000000000001545
  15. Olenick M, Flowers M, Diaz VJ. US veterans and their unique issues: enhancing health care professional awareness. Adv Med Educ Pract. 2015;6:635-639. doi:10.2147/AMEP.S89479
  16. Campbell P, Pope R, Simas V, Canetti E, Schram B, Orr R. The effects of early physiotherapy treatment on musculoskeletal injury outcomes in military personnel: a narrative review. Int J Environ Res Public Health. 2022;19(20):13416. doi:10.3390/ijerph192013416
  17. Gurewich D, Shwartz M, Beilstein-Wedel E, Davila H, Rosen AK. Did access to care improve since passage of the veterans choice act? Differences between rural and urban veterans. Med Care. 2021;59(Suppl 3):S270-S278. doi:10.1097/MLR.0000000000001490
  18. Myers US, Birks A, Grubaugh AL, Axon RN. Flattening the curve by getting ahead of it: how the VA healthcare system is leveraging telehealth to provide continued access to care for rural veterans. J Rural Health. 2021;37(1):194-196. doi:10.1111/jrh.12449
  19. Hale-Gallardo JL, Kreider CM, Jia H, et al. Telerehabilitation for rural veterans: a qualitative assessment of barriers and facilitators to implementation. J Multidiscip Healthc. 2020;13:559-570. doi:10.2147/JMDH.S247267
  20. Kreider CM, Hale-Gallardo J, Kramer JC, et al. Providers’ shift to telerehabilitation at the U.S. Veterans Health Administration during COVID-19: practical applications. Front Public Health. 2022;10:831762. doi:10.3389/fpubh.2022.831762
  21. Cowper-Ripley DC, Jia H, Wang X, et al. Trends in VA telerehabilitation patients and encounters over time and by rurality. Fed Pract. 2019;36(3):122-128.
  22. US Dept of Veterans Affairs, Office of Rural Health. VHA Office of Rural Health. Updated August 30, 2024. Accessed September 23, 2024. https://www.ruralhealth.va.gov/index.asp
  23. National Center for Veterans Analysis and Statistics. Rural Veterans: 2021-2023. April 2023. Accessed September 23, 2024. https://www.datahub.va.gov/stories/s/Rural-Veterans-FY2021-2023/kkh2-eymp/
  24. U.S. Department of Veterans Affairs, Office of Research & Development. Program Guide: 1200.21, VHA Operations Activities That May Constitute Research. January 9, 2019. https://www.research.va.gov/resources/policies/ProgramGuide-1200-21-VHA-Operations-Activities.pdf
  25. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. J Nurs Care Qual. 2016;31(1):1-8. doi:10.1097/NCQ.0000000000000153
  26. US Dept of Veterans Affairs. Veterans Health Administration: Veterans Integrated Service Networks (VISNs). Updated January 29, 2024. Accessed September 23, 2024. https://www.va.gov/HEALTH/visns.asp
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  40. Hynes DM, Edwards S, Hickok A, et al. Veterans’ use of Veterans Health Administration primary care in an era of expanding choice. Med Care. 2021;59(Suppl 3):S292- S300. doi:10.1097/MLR.0000000000001554
References
  1. Congressional Budget Office. The Veterans Community Care Program: Background and Early Effects. October 26, 2021. Accessed September 23, 2024. https://www.cbo.gov/publication/57257
  2. US Dept of Veterans Affairs. Providing Health Care for Veterans. Updated September 10, 2024. Accessed September 23, 2024. https://www.va.gov/health/
  3. Davila H, Rosen AK, Beilstein-Wedel E, Shwartz M, Chatelain LJ, Gurewich D. Rural veterans’ experiences with outpatient care in the Veterans Health Administration versus community care. Med Care. 2021;59(Suppl 3):S286-S291. doi:10.1097/MLR.0000000000001552
  4. Vanneman ME, Wagner TH, Shwartz M, et al. Veterans’ experiences with outpatient care: comparing the Veterans Affairs system with community-based care. Health Aff (Millwood). 2020;39(8):1368-1376. doi:10.1377/hlthaff.2019.01375
  5. Rasmussen P, Farmer CM. The promise and challenges of VA community care: veterans’ issues in focus. Rand Health Q. 2023;10(3):9.
  6. Feyman Y, Legler A, Griffith KN. Appointment wait time data for primary & specialty care in veterans health administration facilities vs. community medical centers. Data Brief. 2021;36:107134. doi:10.1016/j.dib.2021.107134
  7. Kelley AT, Greenstone CL, Kirsh SR. Defining access and the role of community care in the Veterans Health Administration. J Gen Intern Med. 2020;35(5):1584-1585. doi:10.1007/s11606-019-05358-z
  8. Garvin LA, Pugatch M, Gurewich D, Pendergast JN, Miller CJ. Interorganizational care coordination of rural veterans by Veterans Affairs and community care programs: a systematic review. Med Care. 2021;59(Suppl 3):S259-S269. doi:10.1097/MLR.0000000000001542
  9. US Dept of Veterans Affairs, Office of Rural Health. Rural Veterans: Rural Veteran Health Care Challenges. Updated May 14, 2024. Accessed September 23, 2024. https:// www.ruralhealth.va.gov/aboutus/ruralvets.asp
  10. Ohl ME, Carrell M, Thurman A, et al. “Availability of healthcare providers for rural veterans eligible for purchased care under the veterans choice act.” BMC Health Serv Res. 2018;18(1):315. doi:10.1186/s12913-018-3108-8
  11. Mattocks KM, Cunningham KJ, Greenstone C, Atkins D, Rosen AK, Upton M. Innovations in community care programs, policies, and research. Med Care. 2021;59(Suppl 3):S229-S231. doi:10.1097/MLR.0000000000001550
  12. Doyle JM, Streeter RA. Veterans’ location in health professional shortage areas: implications for access to care and workforce supply. Health Serv Res. 2017;52 Suppl 1(Suppl 1):459-480. doi:10.1111/1475-6773.12633
  13. Patzel M, Barnes C, Ramalingam N, et al. Jumping through hoops: community care clinician and staff experiences providing primary care to rural veterans. J Gen Intern Med. 2023;38(Suppl 3):821-828. doi:10.1007/s11606-023-08126-2
  14. Mattocks KM, Kroll-Desrosiers A, Kinney R, Elwy AR, Cunningham KJ, Mengeling MA. Understanding VA’s use of and relationships with community care providers under the MISSION Act. Med Care. 2021;59(Suppl 3):S252-S258. doi:10.1097/MLR.0000000000001545
  15. Olenick M, Flowers M, Diaz VJ. US veterans and their unique issues: enhancing health care professional awareness. Adv Med Educ Pract. 2015;6:635-639. doi:10.2147/AMEP.S89479
  16. Campbell P, Pope R, Simas V, Canetti E, Schram B, Orr R. The effects of early physiotherapy treatment on musculoskeletal injury outcomes in military personnel: a narrative review. Int J Environ Res Public Health. 2022;19(20):13416. doi:10.3390/ijerph192013416
  17. Gurewich D, Shwartz M, Beilstein-Wedel E, Davila H, Rosen AK. Did access to care improve since passage of the veterans choice act? Differences between rural and urban veterans. Med Care. 2021;59(Suppl 3):S270-S278. doi:10.1097/MLR.0000000000001490
  18. Myers US, Birks A, Grubaugh AL, Axon RN. Flattening the curve by getting ahead of it: how the VA healthcare system is leveraging telehealth to provide continued access to care for rural veterans. J Rural Health. 2021;37(1):194-196. doi:10.1111/jrh.12449
  19. Hale-Gallardo JL, Kreider CM, Jia H, et al. Telerehabilitation for rural veterans: a qualitative assessment of barriers and facilitators to implementation. J Multidiscip Healthc. 2020;13:559-570. doi:10.2147/JMDH.S247267
  20. Kreider CM, Hale-Gallardo J, Kramer JC, et al. Providers’ shift to telerehabilitation at the U.S. Veterans Health Administration during COVID-19: practical applications. Front Public Health. 2022;10:831762. doi:10.3389/fpubh.2022.831762
  21. Cowper-Ripley DC, Jia H, Wang X, et al. Trends in VA telerehabilitation patients and encounters over time and by rurality. Fed Pract. 2019;36(3):122-128.
  22. US Dept of Veterans Affairs, Office of Rural Health. VHA Office of Rural Health. Updated August 30, 2024. Accessed September 23, 2024. https://www.ruralhealth.va.gov/index.asp
  23. National Center for Veterans Analysis and Statistics. Rural Veterans: 2021-2023. April 2023. Accessed September 23, 2024. https://www.datahub.va.gov/stories/s/Rural-Veterans-FY2021-2023/kkh2-eymp/
  24. U.S. Department of Veterans Affairs, Office of Research & Development. Program Guide: 1200.21, VHA Operations Activities That May Constitute Research. January 9, 2019. https://www.research.va.gov/resources/policies/ProgramGuide-1200-21-VHA-Operations-Activities.pdf
  25. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. J Nurs Care Qual. 2016;31(1):1-8. doi:10.1097/NCQ.0000000000000153
  26. US Dept of Veterans Affairs. Veterans Health Administration: Veterans Integrated Service Networks (VISNs). Updated January 29, 2024. Accessed September 23, 2024. https://www.va.gov/HEALTH/visns.asp
  27. Stomberg C, Frost A, Becker C, Stang H, Windschitl M, Carrier E. Community Care referral dashboard [Data dashboard]. https://app.powerbigov.us/groups/me/reports/090d22a7-0e1f-4cc5-bea8-0a1b87aa0bd9/ReportSectionacfd03cdebd76ffca9ec [Source not verified]
  28. US Dept of Veterans Affairs. Eligibility for community care outside VA. Updated May 30, 2024. Accessed September 23, 2024. https://www.va.gov/COMMUNITYCARE/programs/veterans/General_Care.asp
  29. US Department of Veterans Affairs, Office of Rural Health. How to define rurality fact sheet. Updated December 2023. Accessed January 28, 2025. https://www.ruralhealth.va.gov/docs/ORH_RuralityFactSheet_508.pdf
  30. Rural-Urban Commuting Area Codes. Economic Research Service, US Dept of Agriculture. Updated September 25, 2023. Accessed September 23, 2024. https://www.ers.usda.gov/data-products/rural-urban-commuting-area-codes.aspx
  31. Gurewich D, Beilstein-Wedel E, Shwartz M, Davila H, Rosen AK. Disparities in wait times for care among US veterans by race and ethnici t y. JAMA Netw Open. 2023;6(1):e2252061. doi:10.1001/jamanetworkopen.2022.52061
  32. U.S. Department of Veterans Affairs, VA Office of Rural Health, Veterans Rural Health Resource Center-Gainesville, GeoSpatial Outcomes Division. VA and Community Healthcare, and VHA Rurality web map application. Published 2023. https://portal.vhagis.inv.vaec.va.gov/arcgis/apps/webappbuilder/index.html [source not verified]
  33. Chartbook on Healthcare for Veterans: National Healthcare Quality and Disparities Report. Agency for Healthcare Research and Quality; November 2020. Accessed September 23, 2024. https://www.ahrq.gov/research/findings/nhqrdr/chartbooks/veterans/index.html
  34. Lum HD, Nearing K, Pimentel CB, Levy CR, Hung WW. Anywhere to anywhere: use of telehealth to increase health care access for older, rural veterans. Public Policy Aging Rep. 2020;30(1):12-18. doi:10.1093/ppar/prz030
  35. Goulet JL, Kerns RD, Bair M, et al. The musculoskeletal diagnosis cohort: examining pain and pain care among veterans. Pain. 2016;157(8):1696-1703. doi:10.1097/j.pain.0000000000000567
  36. US Inflation Calculator. Health Care Inflation in the United States (1948-2024). Accessed September 23, 2024. https://www.usinflationcalculator.com/inflation/health-care-inflation-in-the-united-states/
  37. Cottrell MA, Galea OA, O’Leary SP, Hill AJ, Russell TG. Real-time telerehabilitation for the treatment of musculoskeletal conditions is effective and comparable to standard practice: a systematic review and meta-analysis. Clin Rehabil. 2017;31(5):625-638. doi:10.1177/0269215516645148
  38. Elor A, Conde S, Powel l M, Robbins A, Chen NN, Kurniawan S. Physical therapist impressions of telehealth and virtual reality needs amidst a pandemic. Front Virtual Real. 2022;3. doi:10.3389/frvir.2022.915332
  39. Lee AC, Harada N. Telehealth as a means of health care delivery for physical therapist practice. Phys Ther. 2012;92(3):463-468. doi:10.2522/ptj.20110100
  40. Hynes DM, Edwards S, Hickok A, et al. Veterans’ use of Veterans Health Administration primary care in an era of expanding choice. Med Care. 2021;59(Suppl 3):S292- S300. doi:10.1097/MLR.0000000000001554
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Diet Changes Show Promise in Early Prostate Cancer

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A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

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A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.

Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.

 

Growing Evidence on Diet

Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.

Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.

To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.

Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.

The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.

For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).

For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.

Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.

McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.

Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.

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

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New Clues to Links Between Gulf War Illness and Anthrax Vaccine

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TOPLINE: Gulf War Illness (GWI) symptom severity shows negative correlation with predicted binding affinity of anthrax vaccine antigen to Human Leukocyte Antigen (HLA) Class II molecules. Stronger binding affinity is associated with weaker symptoms, with correlation coefficient r = -0.356 (P < .001).

METHODOLOGY: 

  •      Researchers analyzed 458 Gulf War veterans: 397 men, 61 women, mean (SD) age 56.3 (0.5) years.
  •      The aim was to determine the association between GWI symptom severity and binding affinity of anthrax Protective Antigen to HLA Class II molecules.
  •      Analysis included in silico estimation of predicted binding affinity between 750 15-amino acid length subsequences of protective antigen and specific HLA Class II alleles carried by each participant.
  •      Investigators assessed GWI symptom severity across 6 domains: fatigue, pain, neurological/cognitive/mood, respiratory, gastrointestinal, and dermatologic symptoms that began during or after Gulf War and lasted > 6 months. 

TAKEAWAY:

  •      GWI symptom severity demonstrated significant negative correlation with strength of predicted binding affinity of protective antigen peptides to HLA-II molecules (correlation coefficient [r], −0.356; P < .001), independent of age (partial correlation, −0.376; P < .001).
  •      Researchers identified 180 of 750 (24%) 15-mer epitopes with strong binding affinities to HLA-II molecules, suggesting good potential for CD4+ lymphocyte engagement.
  •      Analysis revealed that DPB1 (15/31, 48%) and DRB1 (13/44, 30%) alleles showed strong binding affinity with Protective Antigen epitopes, while all DQB1 alleles (18/18, 100%) showed no strong binding.
  •      The number of strong binding hits per individual ranged from 3 to 168, indicating wide variability in potential antibody production capability across participants.

IN PRACTICE: "The current findings, demonstrating a robust negative association between HLAanthrax vaccine PA binding and GWI symptom severity, strongly support the hypothesized role of reduced antibody production against anthrax vaccine PA in GWI that most probably underlies the findings supporting anthrax antigen persistence in GWI, in the broader context of antigen persistence in other diseases," Lisa M. James and Apostolos P. Georgopoulos write. 

SOURCE: The study was led by Lisa M. James and Apostolos P. Georgopoulos of the Brain Sciences Center at the Minneapolis Veterans Affairs Health Care System. It was published online on January 18 in Vaccines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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TOPLINE: Gulf War Illness (GWI) symptom severity shows negative correlation with predicted binding affinity of anthrax vaccine antigen to Human Leukocyte Antigen (HLA) Class II molecules. Stronger binding affinity is associated with weaker symptoms, with correlation coefficient r = -0.356 (P < .001).

METHODOLOGY: 

  •      Researchers analyzed 458 Gulf War veterans: 397 men, 61 women, mean (SD) age 56.3 (0.5) years.
  •      The aim was to determine the association between GWI symptom severity and binding affinity of anthrax Protective Antigen to HLA Class II molecules.
  •      Analysis included in silico estimation of predicted binding affinity between 750 15-amino acid length subsequences of protective antigen and specific HLA Class II alleles carried by each participant.
  •      Investigators assessed GWI symptom severity across 6 domains: fatigue, pain, neurological/cognitive/mood, respiratory, gastrointestinal, and dermatologic symptoms that began during or after Gulf War and lasted > 6 months. 

TAKEAWAY:

  •      GWI symptom severity demonstrated significant negative correlation with strength of predicted binding affinity of protective antigen peptides to HLA-II molecules (correlation coefficient [r], −0.356; P < .001), independent of age (partial correlation, −0.376; P < .001).
  •      Researchers identified 180 of 750 (24%) 15-mer epitopes with strong binding affinities to HLA-II molecules, suggesting good potential for CD4+ lymphocyte engagement.
  •      Analysis revealed that DPB1 (15/31, 48%) and DRB1 (13/44, 30%) alleles showed strong binding affinity with Protective Antigen epitopes, while all DQB1 alleles (18/18, 100%) showed no strong binding.
  •      The number of strong binding hits per individual ranged from 3 to 168, indicating wide variability in potential antibody production capability across participants.

IN PRACTICE: "The current findings, demonstrating a robust negative association between HLAanthrax vaccine PA binding and GWI symptom severity, strongly support the hypothesized role of reduced antibody production against anthrax vaccine PA in GWI that most probably underlies the findings supporting anthrax antigen persistence in GWI, in the broader context of antigen persistence in other diseases," Lisa M. James and Apostolos P. Georgopoulos write. 

SOURCE: The study was led by Lisa M. James and Apostolos P. Georgopoulos of the Brain Sciences Center at the Minneapolis Veterans Affairs Health Care System. It was published online on January 18 in Vaccines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Gulf War Illness (GWI) symptom severity shows negative correlation with predicted binding affinity of anthrax vaccine antigen to Human Leukocyte Antigen (HLA) Class II molecules. Stronger binding affinity is associated with weaker symptoms, with correlation coefficient r = -0.356 (P < .001).

METHODOLOGY: 

  •      Researchers analyzed 458 Gulf War veterans: 397 men, 61 women, mean (SD) age 56.3 (0.5) years.
  •      The aim was to determine the association between GWI symptom severity and binding affinity of anthrax Protective Antigen to HLA Class II molecules.
  •      Analysis included in silico estimation of predicted binding affinity between 750 15-amino acid length subsequences of protective antigen and specific HLA Class II alleles carried by each participant.
  •      Investigators assessed GWI symptom severity across 6 domains: fatigue, pain, neurological/cognitive/mood, respiratory, gastrointestinal, and dermatologic symptoms that began during or after Gulf War and lasted > 6 months. 

TAKEAWAY:

  •      GWI symptom severity demonstrated significant negative correlation with strength of predicted binding affinity of protective antigen peptides to HLA-II molecules (correlation coefficient [r], −0.356; P < .001), independent of age (partial correlation, −0.376; P < .001).
  •      Researchers identified 180 of 750 (24%) 15-mer epitopes with strong binding affinities to HLA-II molecules, suggesting good potential for CD4+ lymphocyte engagement.
  •      Analysis revealed that DPB1 (15/31, 48%) and DRB1 (13/44, 30%) alleles showed strong binding affinity with Protective Antigen epitopes, while all DQB1 alleles (18/18, 100%) showed no strong binding.
  •      The number of strong binding hits per individual ranged from 3 to 168, indicating wide variability in potential antibody production capability across participants.

IN PRACTICE: "The current findings, demonstrating a robust negative association between HLAanthrax vaccine PA binding and GWI symptom severity, strongly support the hypothesized role of reduced antibody production against anthrax vaccine PA in GWI that most probably underlies the findings supporting anthrax antigen persistence in GWI, in the broader context of antigen persistence in other diseases," Lisa M. James and Apostolos P. Georgopoulos write. 

SOURCE: The study was led by Lisa M. James and Apostolos P. Georgopoulos of the Brain Sciences Center at the Minneapolis Veterans Affairs Health Care System. It was published online on January 18 in Vaccines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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Vasculitis Patients Need Multiple COVID Vaccine Boosters

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People with vasculitis may need at least three or four vaccinations for COVID-19 before they start to show an immune response against SARS-CoV-2 infection, new research has suggested.

In a longitudinal retrospective study, serum antibody neutralization against the Omicron variant of the virus and its descendants was found to be “largely absent” after the first two doses of COVID-19 vaccine had been given to patients. But increasing neutralizing antibody titers were seen after both the third and fourth vaccine boosters had been administered.

Results also showed that the more recently people had been treated with the B cell–depleting therapy rituximab, the lower the levels of immunogenicity that were achieved, and thus protection against SARS-CoV-2.

“Our results have significant implications for individuals treated with rituximab in the post-Omicron era, highlighting the value of additive boosters in affirming increasing protection in clinically vulnerable populations,” the team behind the work at the University of Cambridge in England, has reported in Science Advances.

Moreover, because the use of rituximab reduced the neutralization of not just wild-type (WT) Omicron but also the Omicron-descendant variants BA.1, BA.2, BA.4, and XBB, this highlights “the urgent need for additional adjunctive strategies to enhance vaccine-induced immunity as well as preferential access for such patients to updated vaccines using spike from now circulating Omicron lineages,” the team added.

 

Studying Humoral Responses to SARS-CoV-2 Vaccines

Corresponding author Ravindra K. Gupta, BMBCh, MA, MPH, PhD, told this news organization that studying humoral responses to SARS-CoV-2 vaccines in immunocompromised individuals such as those with vasculitis was important for two main reasons.

“It is really important at individual level for their own health, of course, but also because we know that variants of concern have often evolved and developed within patients and can then spread in wider populations,” he said.

Gupta, who is professor of clinical microbiology at the Cambridge Institute for Therapeutic Immunology & Infectious Disease added: “We believe that the variants of concern that we’re having to deal with right now, including Omicron, have come from such [immunocompromised] individuals.”

Omicron “was a big shift,” Gupta noted. “It had a lot of new mutations on it, so it was almost like a new strain of the virus.” Few studies have looked at the longitudinal immunogenicity proffered by COVID vaccines in the post-Omicron era, particularly in those with vasculitis who are often treated with immunosuppressive drugs, including rituximab.

 

Two-Pronged Study Approach

For the study, a population of immunocompromised individuals diagnosed with vasculitis who had been treated with rituximab in the past 5 years was identified. Just over half (58%) had received adenovirus-based AZD1222/ChAdOx1 nCoV-19 (AstraZeneca-Oxford; AZN) and 37% BNT162b2 (Pfizer-BioNTech; mRNA) as their primary vaccines. Patients with antineutrophil cytoplasmic antibody–associated vasculitis comprised the majority of those who received rituximab (83%), compared with less than half of those who did not take rituximab (48%).

A two-pronged approach was taken with the researchers first measuring neutralizing antibody titers before and 30 days after four successive COVID vaccinations in a group of 32 individuals with available samples. They then performed a cross-sectional, case-control study in 95 individuals to look at neutralizing antibody titers and antibody-dependent cell-mediated cytotoxicity (ADCC) in individuals who had (n = 64) and had not (n = 31) been treated with rituximab in the past 5 years and had samples available after their third and fourth COVID vaccinations.

The first analysis was done to see how people were responding to vaccination over time. “That told us that there was a problem with the first two doses and that we got some response after doses three and four, but the response was uniformly quite poor against the new variants of concern,” Gupta said.

A human embryonic kidney cell model had been used to determine individuals’ neutralizing antibody titers in response to WT, BA.1, BA.2, BA.4, and XBB pseudotyped viruses. After the first and second COVID vaccinations, the geometric mean titer (GMT) against each variant barely increased from a baseline of 40.0. The greatest increases in GMT was seen with the WT virus, at 43.7, 90.7, 256.3, and 394.2, after the first, second, third and fourth doses, respectively. The lowest increases in GMT were seen with the XBB variant, with respective values of 40.0, 40.8, 45.7, and 53.9.

 

Incremental Benefit Offers Some ‘Reassurance’

Vasculitis specialist Rona Smith, MA, MB BChir, MD, who was one of the authors of the paper, told this news organization separately that the results showed there was “an incremental benefit of having COVID vaccinations,” which “offers a little bit of reassurance” that there can be an immune response in people with vasculitis.

Although results of the cross-sectional study showed that there was a significant dampening effect of rituximab treatment on the immune response, “I don’t think it’s an isolated effect in our [vasculitis] patients,” Smith suggested, adding the results were “probably still relevant to patients who receive routine dosing of rituximab for other conditions.”

Neutralizing antibody titers were consistently lower among individuals who had been treated with rituximab vs those who had not, with treatment in the past 18 months found to significantly impair immunogenicity.

The ADCC response was better preserved than the neutralizing antibody response, Gupta said, although it was still significantly lower in the rituximab-treated than in the non–rituximab-treated patients.

 

When to Vaccinate in Vasculitis?

Regarding when to give vaccines to people with vasculitis, Smith said: “Current recommendations are that patients should receive any vaccines that they’re offered routinely, whether that be COVID vaccines, flu vaccines, pneumococcal vaccines.”

As for the timing of those vaccinations, she observed that the current thinking was that vaccinations should “ideally be at least 1 month before a rituximab treatment, and ideally 3-4 [months] after their last dose. However, as many patients are on a 6-month dosing cycle, it can be difficult for some of them to find a suitable time window to have the COVID vaccine when it is offered.”

Additional precautions, such as wearing masks in crowded places and avoiding visits to acutely unwell friends or relatives, may still be prudent, Smith acknowledged, but he was clear that people should not be locking themselves away as they did during the COVID-19 pandemic.

When advising patients, “our general recommendation is that it is better to have a vaccine than not, but we can’t guarantee how well you will respond to it, but some response is better than none,” Smith said.

The study was independently supported. Gupta had no relevant financial relationships to disclose. Smith was a coauthor of the paper and has received research grant funding from Union Therapeutics, GlaxoSmithKline/Vir Biotechnology, Addenbrooke’s Charitable Trust, and Vasculitis UK. Another coauthor reported receiving research grants from CSL Vifor, Roche, and GlaxoSmithKline and advisory board, consultancy, and lecture fees from Roche and CSL Vifor.

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

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People with vasculitis may need at least three or four vaccinations for COVID-19 before they start to show an immune response against SARS-CoV-2 infection, new research has suggested.

In a longitudinal retrospective study, serum antibody neutralization against the Omicron variant of the virus and its descendants was found to be “largely absent” after the first two doses of COVID-19 vaccine had been given to patients. But increasing neutralizing antibody titers were seen after both the third and fourth vaccine boosters had been administered.

Results also showed that the more recently people had been treated with the B cell–depleting therapy rituximab, the lower the levels of immunogenicity that were achieved, and thus protection against SARS-CoV-2.

“Our results have significant implications for individuals treated with rituximab in the post-Omicron era, highlighting the value of additive boosters in affirming increasing protection in clinically vulnerable populations,” the team behind the work at the University of Cambridge in England, has reported in Science Advances.

Moreover, because the use of rituximab reduced the neutralization of not just wild-type (WT) Omicron but also the Omicron-descendant variants BA.1, BA.2, BA.4, and XBB, this highlights “the urgent need for additional adjunctive strategies to enhance vaccine-induced immunity as well as preferential access for such patients to updated vaccines using spike from now circulating Omicron lineages,” the team added.

 

Studying Humoral Responses to SARS-CoV-2 Vaccines

Corresponding author Ravindra K. Gupta, BMBCh, MA, MPH, PhD, told this news organization that studying humoral responses to SARS-CoV-2 vaccines in immunocompromised individuals such as those with vasculitis was important for two main reasons.

“It is really important at individual level for their own health, of course, but also because we know that variants of concern have often evolved and developed within patients and can then spread in wider populations,” he said.

Gupta, who is professor of clinical microbiology at the Cambridge Institute for Therapeutic Immunology & Infectious Disease added: “We believe that the variants of concern that we’re having to deal with right now, including Omicron, have come from such [immunocompromised] individuals.”

Omicron “was a big shift,” Gupta noted. “It had a lot of new mutations on it, so it was almost like a new strain of the virus.” Few studies have looked at the longitudinal immunogenicity proffered by COVID vaccines in the post-Omicron era, particularly in those with vasculitis who are often treated with immunosuppressive drugs, including rituximab.

 

Two-Pronged Study Approach

For the study, a population of immunocompromised individuals diagnosed with vasculitis who had been treated with rituximab in the past 5 years was identified. Just over half (58%) had received adenovirus-based AZD1222/ChAdOx1 nCoV-19 (AstraZeneca-Oxford; AZN) and 37% BNT162b2 (Pfizer-BioNTech; mRNA) as their primary vaccines. Patients with antineutrophil cytoplasmic antibody–associated vasculitis comprised the majority of those who received rituximab (83%), compared with less than half of those who did not take rituximab (48%).

A two-pronged approach was taken with the researchers first measuring neutralizing antibody titers before and 30 days after four successive COVID vaccinations in a group of 32 individuals with available samples. They then performed a cross-sectional, case-control study in 95 individuals to look at neutralizing antibody titers and antibody-dependent cell-mediated cytotoxicity (ADCC) in individuals who had (n = 64) and had not (n = 31) been treated with rituximab in the past 5 years and had samples available after their third and fourth COVID vaccinations.

The first analysis was done to see how people were responding to vaccination over time. “That told us that there was a problem with the first two doses and that we got some response after doses three and four, but the response was uniformly quite poor against the new variants of concern,” Gupta said.

A human embryonic kidney cell model had been used to determine individuals’ neutralizing antibody titers in response to WT, BA.1, BA.2, BA.4, and XBB pseudotyped viruses. After the first and second COVID vaccinations, the geometric mean titer (GMT) against each variant barely increased from a baseline of 40.0. The greatest increases in GMT was seen with the WT virus, at 43.7, 90.7, 256.3, and 394.2, after the first, second, third and fourth doses, respectively. The lowest increases in GMT were seen with the XBB variant, with respective values of 40.0, 40.8, 45.7, and 53.9.

 

Incremental Benefit Offers Some ‘Reassurance’

Vasculitis specialist Rona Smith, MA, MB BChir, MD, who was one of the authors of the paper, told this news organization separately that the results showed there was “an incremental benefit of having COVID vaccinations,” which “offers a little bit of reassurance” that there can be an immune response in people with vasculitis.

Although results of the cross-sectional study showed that there was a significant dampening effect of rituximab treatment on the immune response, “I don’t think it’s an isolated effect in our [vasculitis] patients,” Smith suggested, adding the results were “probably still relevant to patients who receive routine dosing of rituximab for other conditions.”

Neutralizing antibody titers were consistently lower among individuals who had been treated with rituximab vs those who had not, with treatment in the past 18 months found to significantly impair immunogenicity.

The ADCC response was better preserved than the neutralizing antibody response, Gupta said, although it was still significantly lower in the rituximab-treated than in the non–rituximab-treated patients.

 

When to Vaccinate in Vasculitis?

Regarding when to give vaccines to people with vasculitis, Smith said: “Current recommendations are that patients should receive any vaccines that they’re offered routinely, whether that be COVID vaccines, flu vaccines, pneumococcal vaccines.”

As for the timing of those vaccinations, she observed that the current thinking was that vaccinations should “ideally be at least 1 month before a rituximab treatment, and ideally 3-4 [months] after their last dose. However, as many patients are on a 6-month dosing cycle, it can be difficult for some of them to find a suitable time window to have the COVID vaccine when it is offered.”

Additional precautions, such as wearing masks in crowded places and avoiding visits to acutely unwell friends or relatives, may still be prudent, Smith acknowledged, but he was clear that people should not be locking themselves away as they did during the COVID-19 pandemic.

When advising patients, “our general recommendation is that it is better to have a vaccine than not, but we can’t guarantee how well you will respond to it, but some response is better than none,” Smith said.

The study was independently supported. Gupta had no relevant financial relationships to disclose. Smith was a coauthor of the paper and has received research grant funding from Union Therapeutics, GlaxoSmithKline/Vir Biotechnology, Addenbrooke’s Charitable Trust, and Vasculitis UK. Another coauthor reported receiving research grants from CSL Vifor, Roche, and GlaxoSmithKline and advisory board, consultancy, and lecture fees from Roche and CSL Vifor.

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

People with vasculitis may need at least three or four vaccinations for COVID-19 before they start to show an immune response against SARS-CoV-2 infection, new research has suggested.

In a longitudinal retrospective study, serum antibody neutralization against the Omicron variant of the virus and its descendants was found to be “largely absent” after the first two doses of COVID-19 vaccine had been given to patients. But increasing neutralizing antibody titers were seen after both the third and fourth vaccine boosters had been administered.

Results also showed that the more recently people had been treated with the B cell–depleting therapy rituximab, the lower the levels of immunogenicity that were achieved, and thus protection against SARS-CoV-2.

“Our results have significant implications for individuals treated with rituximab in the post-Omicron era, highlighting the value of additive boosters in affirming increasing protection in clinically vulnerable populations,” the team behind the work at the University of Cambridge in England, has reported in Science Advances.

Moreover, because the use of rituximab reduced the neutralization of not just wild-type (WT) Omicron but also the Omicron-descendant variants BA.1, BA.2, BA.4, and XBB, this highlights “the urgent need for additional adjunctive strategies to enhance vaccine-induced immunity as well as preferential access for such patients to updated vaccines using spike from now circulating Omicron lineages,” the team added.

 

Studying Humoral Responses to SARS-CoV-2 Vaccines

Corresponding author Ravindra K. Gupta, BMBCh, MA, MPH, PhD, told this news organization that studying humoral responses to SARS-CoV-2 vaccines in immunocompromised individuals such as those with vasculitis was important for two main reasons.

“It is really important at individual level for their own health, of course, but also because we know that variants of concern have often evolved and developed within patients and can then spread in wider populations,” he said.

Gupta, who is professor of clinical microbiology at the Cambridge Institute for Therapeutic Immunology & Infectious Disease added: “We believe that the variants of concern that we’re having to deal with right now, including Omicron, have come from such [immunocompromised] individuals.”

Omicron “was a big shift,” Gupta noted. “It had a lot of new mutations on it, so it was almost like a new strain of the virus.” Few studies have looked at the longitudinal immunogenicity proffered by COVID vaccines in the post-Omicron era, particularly in those with vasculitis who are often treated with immunosuppressive drugs, including rituximab.

 

Two-Pronged Study Approach

For the study, a population of immunocompromised individuals diagnosed with vasculitis who had been treated with rituximab in the past 5 years was identified. Just over half (58%) had received adenovirus-based AZD1222/ChAdOx1 nCoV-19 (AstraZeneca-Oxford; AZN) and 37% BNT162b2 (Pfizer-BioNTech; mRNA) as their primary vaccines. Patients with antineutrophil cytoplasmic antibody–associated vasculitis comprised the majority of those who received rituximab (83%), compared with less than half of those who did not take rituximab (48%).

A two-pronged approach was taken with the researchers first measuring neutralizing antibody titers before and 30 days after four successive COVID vaccinations in a group of 32 individuals with available samples. They then performed a cross-sectional, case-control study in 95 individuals to look at neutralizing antibody titers and antibody-dependent cell-mediated cytotoxicity (ADCC) in individuals who had (n = 64) and had not (n = 31) been treated with rituximab in the past 5 years and had samples available after their third and fourth COVID vaccinations.

The first analysis was done to see how people were responding to vaccination over time. “That told us that there was a problem with the first two doses and that we got some response after doses three and four, but the response was uniformly quite poor against the new variants of concern,” Gupta said.

A human embryonic kidney cell model had been used to determine individuals’ neutralizing antibody titers in response to WT, BA.1, BA.2, BA.4, and XBB pseudotyped viruses. After the first and second COVID vaccinations, the geometric mean titer (GMT) against each variant barely increased from a baseline of 40.0. The greatest increases in GMT was seen with the WT virus, at 43.7, 90.7, 256.3, and 394.2, after the first, second, third and fourth doses, respectively. The lowest increases in GMT were seen with the XBB variant, with respective values of 40.0, 40.8, 45.7, and 53.9.

 

Incremental Benefit Offers Some ‘Reassurance’

Vasculitis specialist Rona Smith, MA, MB BChir, MD, who was one of the authors of the paper, told this news organization separately that the results showed there was “an incremental benefit of having COVID vaccinations,” which “offers a little bit of reassurance” that there can be an immune response in people with vasculitis.

Although results of the cross-sectional study showed that there was a significant dampening effect of rituximab treatment on the immune response, “I don’t think it’s an isolated effect in our [vasculitis] patients,” Smith suggested, adding the results were “probably still relevant to patients who receive routine dosing of rituximab for other conditions.”

Neutralizing antibody titers were consistently lower among individuals who had been treated with rituximab vs those who had not, with treatment in the past 18 months found to significantly impair immunogenicity.

The ADCC response was better preserved than the neutralizing antibody response, Gupta said, although it was still significantly lower in the rituximab-treated than in the non–rituximab-treated patients.

 

When to Vaccinate in Vasculitis?

Regarding when to give vaccines to people with vasculitis, Smith said: “Current recommendations are that patients should receive any vaccines that they’re offered routinely, whether that be COVID vaccines, flu vaccines, pneumococcal vaccines.”

As for the timing of those vaccinations, she observed that the current thinking was that vaccinations should “ideally be at least 1 month before a rituximab treatment, and ideally 3-4 [months] after their last dose. However, as many patients are on a 6-month dosing cycle, it can be difficult for some of them to find a suitable time window to have the COVID vaccine when it is offered.”

Additional precautions, such as wearing masks in crowded places and avoiding visits to acutely unwell friends or relatives, may still be prudent, Smith acknowledged, but he was clear that people should not be locking themselves away as they did during the COVID-19 pandemic.

When advising patients, “our general recommendation is that it is better to have a vaccine than not, but we can’t guarantee how well you will respond to it, but some response is better than none,” Smith said.

The study was independently supported. Gupta had no relevant financial relationships to disclose. Smith was a coauthor of the paper and has received research grant funding from Union Therapeutics, GlaxoSmithKline/Vir Biotechnology, Addenbrooke’s Charitable Trust, and Vasculitis UK. Another coauthor reported receiving research grants from CSL Vifor, Roche, and GlaxoSmithKline and advisory board, consultancy, and lecture fees from Roche and CSL Vifor.

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

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New Five-Type Index Provides Doctors Guide for Long COVID

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A new analysis of long-COVID patients has identified five distinct subtypes that researchers say will help doctors diagnose the condition.

The new five-type index, developed by federal researchers with the National Institutes of Health’s RECOVER COVID Initiative, identified the most common symptoms in 14,000 people with long COVID, with data from an additional 4000 people added to the updated 2024 index.

By using the index, physicians and researchers can better understand the condition, which is difficult to treat and diagnose because no standard definitions or therapies have been developed. Doctors can use the index to offer more targeted care and help patients manage their symptoms more effectively.

The index may also help researchers find more treatments for long COVID. Because long COVID can affect so many different parts of the body, it will take time to fully understand how to treat it, but studies like this are making progress in the right direction, experts said.

This new index uses an updated point system, where points are allotted to each symptom in a list of the 44 most reported symptoms in people with likely long COVID based on how often they occur. Among people in the study with prior COVID infection, 2213 (18%) met the threshold for long COVID.

The 44 most common symptoms were then distributed among 5 subtypes, with each representing a difference in impact on quality of life and overall health. The most common symptoms were fatigue (85.8%), postexertional malaise (87.4%), and postexertional soreness (75.0%) — where persistent fatigue and discomfort occur after physical or mental exertion — dizziness (65.8%), brain fog (63.8%), gastrointestinal symptoms (59.3%), and palpitations (58%).

For those with prior COVID infection, symptoms were more prevalent in all cases.

 

Subtype 1

Those grouped into subtype 1 did not report a high incidence of impact on quality of life, physical health, or daily function. Only 21% of people in subtype 1 reported a “poor or fair quality of life.”

A change in smell or taste — usually a symptom that’s bothersome but doesn’t seriously impact overall health — was most present in subtype 1, with 100% of people in subtype 1 reporting it.

The only other symptoms in over 50% of people with subtype 1— which were 490 of the 2213 with prior COVID infection — were fatigue (66%), postexertional malaise (53%), and postexertional soreness (55%).

Though these two symptoms can certainly impact quality of life, they became much more prevalent in other subtypes.

 

Subtype 2

The prevalence of possibly debilitating symptoms like postexertional malaise (94%), fatigue (81%), and chronic cough (100%) rose dramatically in people grouped into subtype 2. 

Plus, 25% of people in subtype 2 reported a “poor or fair quality of life. Postexertional malaise, I think, is probably one of the most debilitating of the symptoms. When somebody comes in and tells me that they’re tired and I think they might have long COVID, the first thing I try to do is see if it is postexertional malaise vs just postinfectious fatigue,” said Lisa Sanders, MD, medical director of Yale’s Long Covid Multidisciplinary Care Center in New Haven, Connecticut.

Postinfectious fatigue usually resolves much more quickly than postexertional malaise. The latter accounts for several symptoms as also associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a chronic illness that causes severe fatigue and makes it difficult for sufferers to perform routine, daily activities.

“Postexertional malaise is an additive symptom of ME/CFS, and that can take a long time to resolve,” Sanders added.

The similarity between these two symptoms highlights the importance that physicians must place in scrutinizing symptoms to a high degree when they suspect a patient of having long COVID, experts said. By doing so, clinicians can unveil the mask of overlapping symptoms between long COVID symptoms and symptoms of other illnesses.

 

Subtype 3

About 37% of people grouped in subtype 3 reported a poor or fair quality of life, a significant rise from subtypes 1 and 2.

Fatigue symptoms were reported by 92%, whereas 82% reported postexertional soreness, and 70% reported dizziness. Additionally, 100% of people in subtype 3 reported brain fog as a symptom.

Sanders said these symptoms are also common in people with postural orthostatic tachycardia syndrome. This condition results from a reduced volume of blood returning to the heart after standing up, which leads to an abnormally fast heart rate. Palpitations and fainting can then occur.

Brain fog can be especially debilitating in people who are used to multitasking. With brain fog, people accustomed to easily alternating between tasks or doing multiple tasks at once can only do one thing at a time. This can cause stress and an overload of thoughts, even precipitating a change in careers if severe enough.

Though brain fog tends to resolve within 6-9 months after infection, it can last up to 18 months or more. Experts say doctors should always be on the lookout if a patient complains they have trouble concentrating or multitasking in the months after a COVID infection. A neurological exam and cognitive testing can identify abnormalities in brain function.

 

Subtype 4

About 40% of people in the study grouped into subtype 4 reported a poor or fair quality of life, a modest increase from those with subtype 3. About 65% reported symptoms of brain fog and 92% reported palpitations.

Dizziness was also prevalent at 71%, whereas 60% reported gastrointestinal issues, and 36% said they experienced fever, sweats, and chills.

Nearly 700 of the 2213 people fell into this subtype group, by far the highest number.

 

Subtype 5

A whopping 66% of people in subtype 5 reported a poor to fair quality of life. These people usually reported multisystem symptoms.

In terms of prevalence rises across the spectrum of 44 common long-COVID symptoms, 99% reported shortness of breath; 98%, postexertional soreness; 94%, dizziness; 92%, postexertional malaise; 80%, GI problems; 78%, weakness; and 69%, chest pain.

A higher proportion of Hispanic and multiracial participants were classified as having subtype 5. Also, according to the study, “higher proportions of unvaccinated participants and those with SARS-CoV-2 infection before circulation of the Omicron variant were in subtype 5.”

This suggests the severity of the Delta variant of COVID-19 be linked to some of the worst long COVID symptoms, but further study would have to be done to conclusively determine may be just a correlation.

 

When Do Symptoms Resolve?

According to Sanders, around 17 million Americans are thought to have long COVID. Although 90%-100% of people typically recover within 3 years, that still leaves possibly around 5% of those who don’t recover.

“What people usually say is, ‘I got COVID, and I never quite recovered,” Sanders said.

“Five percent of 17 million turns out to be a lot. It’s a lot of suffering,” she added. “I would say that the most common symptoms are fatigue, brain fog, anosmia or dysgeusia, and sleep disorders,” as evidenced by the high percentage of people in certain subtypes of the study reporting a poor quality of life.

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

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A new analysis of long-COVID patients has identified five distinct subtypes that researchers say will help doctors diagnose the condition.

The new five-type index, developed by federal researchers with the National Institutes of Health’s RECOVER COVID Initiative, identified the most common symptoms in 14,000 people with long COVID, with data from an additional 4000 people added to the updated 2024 index.

By using the index, physicians and researchers can better understand the condition, which is difficult to treat and diagnose because no standard definitions or therapies have been developed. Doctors can use the index to offer more targeted care and help patients manage their symptoms more effectively.

The index may also help researchers find more treatments for long COVID. Because long COVID can affect so many different parts of the body, it will take time to fully understand how to treat it, but studies like this are making progress in the right direction, experts said.

This new index uses an updated point system, where points are allotted to each symptom in a list of the 44 most reported symptoms in people with likely long COVID based on how often they occur. Among people in the study with prior COVID infection, 2213 (18%) met the threshold for long COVID.

The 44 most common symptoms were then distributed among 5 subtypes, with each representing a difference in impact on quality of life and overall health. The most common symptoms were fatigue (85.8%), postexertional malaise (87.4%), and postexertional soreness (75.0%) — where persistent fatigue and discomfort occur after physical or mental exertion — dizziness (65.8%), brain fog (63.8%), gastrointestinal symptoms (59.3%), and palpitations (58%).

For those with prior COVID infection, symptoms were more prevalent in all cases.

 

Subtype 1

Those grouped into subtype 1 did not report a high incidence of impact on quality of life, physical health, or daily function. Only 21% of people in subtype 1 reported a “poor or fair quality of life.”

A change in smell or taste — usually a symptom that’s bothersome but doesn’t seriously impact overall health — was most present in subtype 1, with 100% of people in subtype 1 reporting it.

The only other symptoms in over 50% of people with subtype 1— which were 490 of the 2213 with prior COVID infection — were fatigue (66%), postexertional malaise (53%), and postexertional soreness (55%).

Though these two symptoms can certainly impact quality of life, they became much more prevalent in other subtypes.

 

Subtype 2

The prevalence of possibly debilitating symptoms like postexertional malaise (94%), fatigue (81%), and chronic cough (100%) rose dramatically in people grouped into subtype 2. 

Plus, 25% of people in subtype 2 reported a “poor or fair quality of life. Postexertional malaise, I think, is probably one of the most debilitating of the symptoms. When somebody comes in and tells me that they’re tired and I think they might have long COVID, the first thing I try to do is see if it is postexertional malaise vs just postinfectious fatigue,” said Lisa Sanders, MD, medical director of Yale’s Long Covid Multidisciplinary Care Center in New Haven, Connecticut.

Postinfectious fatigue usually resolves much more quickly than postexertional malaise. The latter accounts for several symptoms as also associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a chronic illness that causes severe fatigue and makes it difficult for sufferers to perform routine, daily activities.

“Postexertional malaise is an additive symptom of ME/CFS, and that can take a long time to resolve,” Sanders added.

The similarity between these two symptoms highlights the importance that physicians must place in scrutinizing symptoms to a high degree when they suspect a patient of having long COVID, experts said. By doing so, clinicians can unveil the mask of overlapping symptoms between long COVID symptoms and symptoms of other illnesses.

 

Subtype 3

About 37% of people grouped in subtype 3 reported a poor or fair quality of life, a significant rise from subtypes 1 and 2.

Fatigue symptoms were reported by 92%, whereas 82% reported postexertional soreness, and 70% reported dizziness. Additionally, 100% of people in subtype 3 reported brain fog as a symptom.

Sanders said these symptoms are also common in people with postural orthostatic tachycardia syndrome. This condition results from a reduced volume of blood returning to the heart after standing up, which leads to an abnormally fast heart rate. Palpitations and fainting can then occur.

Brain fog can be especially debilitating in people who are used to multitasking. With brain fog, people accustomed to easily alternating between tasks or doing multiple tasks at once can only do one thing at a time. This can cause stress and an overload of thoughts, even precipitating a change in careers if severe enough.

Though brain fog tends to resolve within 6-9 months after infection, it can last up to 18 months or more. Experts say doctors should always be on the lookout if a patient complains they have trouble concentrating or multitasking in the months after a COVID infection. A neurological exam and cognitive testing can identify abnormalities in brain function.

 

Subtype 4

About 40% of people in the study grouped into subtype 4 reported a poor or fair quality of life, a modest increase from those with subtype 3. About 65% reported symptoms of brain fog and 92% reported palpitations.

Dizziness was also prevalent at 71%, whereas 60% reported gastrointestinal issues, and 36% said they experienced fever, sweats, and chills.

Nearly 700 of the 2213 people fell into this subtype group, by far the highest number.

 

Subtype 5

A whopping 66% of people in subtype 5 reported a poor to fair quality of life. These people usually reported multisystem symptoms.

In terms of prevalence rises across the spectrum of 44 common long-COVID symptoms, 99% reported shortness of breath; 98%, postexertional soreness; 94%, dizziness; 92%, postexertional malaise; 80%, GI problems; 78%, weakness; and 69%, chest pain.

A higher proportion of Hispanic and multiracial participants were classified as having subtype 5. Also, according to the study, “higher proportions of unvaccinated participants and those with SARS-CoV-2 infection before circulation of the Omicron variant were in subtype 5.”

This suggests the severity of the Delta variant of COVID-19 be linked to some of the worst long COVID symptoms, but further study would have to be done to conclusively determine may be just a correlation.

 

When Do Symptoms Resolve?

According to Sanders, around 17 million Americans are thought to have long COVID. Although 90%-100% of people typically recover within 3 years, that still leaves possibly around 5% of those who don’t recover.

“What people usually say is, ‘I got COVID, and I never quite recovered,” Sanders said.

“Five percent of 17 million turns out to be a lot. It’s a lot of suffering,” she added. “I would say that the most common symptoms are fatigue, brain fog, anosmia or dysgeusia, and sleep disorders,” as evidenced by the high percentage of people in certain subtypes of the study reporting a poor quality of life.

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

A new analysis of long-COVID patients has identified five distinct subtypes that researchers say will help doctors diagnose the condition.

The new five-type index, developed by federal researchers with the National Institutes of Health’s RECOVER COVID Initiative, identified the most common symptoms in 14,000 people with long COVID, with data from an additional 4000 people added to the updated 2024 index.

By using the index, physicians and researchers can better understand the condition, which is difficult to treat and diagnose because no standard definitions or therapies have been developed. Doctors can use the index to offer more targeted care and help patients manage their symptoms more effectively.

The index may also help researchers find more treatments for long COVID. Because long COVID can affect so many different parts of the body, it will take time to fully understand how to treat it, but studies like this are making progress in the right direction, experts said.

This new index uses an updated point system, where points are allotted to each symptom in a list of the 44 most reported symptoms in people with likely long COVID based on how often they occur. Among people in the study with prior COVID infection, 2213 (18%) met the threshold for long COVID.

The 44 most common symptoms were then distributed among 5 subtypes, with each representing a difference in impact on quality of life and overall health. The most common symptoms were fatigue (85.8%), postexertional malaise (87.4%), and postexertional soreness (75.0%) — where persistent fatigue and discomfort occur after physical or mental exertion — dizziness (65.8%), brain fog (63.8%), gastrointestinal symptoms (59.3%), and palpitations (58%).

For those with prior COVID infection, symptoms were more prevalent in all cases.

 

Subtype 1

Those grouped into subtype 1 did not report a high incidence of impact on quality of life, physical health, or daily function. Only 21% of people in subtype 1 reported a “poor or fair quality of life.”

A change in smell or taste — usually a symptom that’s bothersome but doesn’t seriously impact overall health — was most present in subtype 1, with 100% of people in subtype 1 reporting it.

The only other symptoms in over 50% of people with subtype 1— which were 490 of the 2213 with prior COVID infection — were fatigue (66%), postexertional malaise (53%), and postexertional soreness (55%).

Though these two symptoms can certainly impact quality of life, they became much more prevalent in other subtypes.

 

Subtype 2

The prevalence of possibly debilitating symptoms like postexertional malaise (94%), fatigue (81%), and chronic cough (100%) rose dramatically in people grouped into subtype 2. 

Plus, 25% of people in subtype 2 reported a “poor or fair quality of life. Postexertional malaise, I think, is probably one of the most debilitating of the symptoms. When somebody comes in and tells me that they’re tired and I think they might have long COVID, the first thing I try to do is see if it is postexertional malaise vs just postinfectious fatigue,” said Lisa Sanders, MD, medical director of Yale’s Long Covid Multidisciplinary Care Center in New Haven, Connecticut.

Postinfectious fatigue usually resolves much more quickly than postexertional malaise. The latter accounts for several symptoms as also associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a chronic illness that causes severe fatigue and makes it difficult for sufferers to perform routine, daily activities.

“Postexertional malaise is an additive symptom of ME/CFS, and that can take a long time to resolve,” Sanders added.

The similarity between these two symptoms highlights the importance that physicians must place in scrutinizing symptoms to a high degree when they suspect a patient of having long COVID, experts said. By doing so, clinicians can unveil the mask of overlapping symptoms between long COVID symptoms and symptoms of other illnesses.

 

Subtype 3

About 37% of people grouped in subtype 3 reported a poor or fair quality of life, a significant rise from subtypes 1 and 2.

Fatigue symptoms were reported by 92%, whereas 82% reported postexertional soreness, and 70% reported dizziness. Additionally, 100% of people in subtype 3 reported brain fog as a symptom.

Sanders said these symptoms are also common in people with postural orthostatic tachycardia syndrome. This condition results from a reduced volume of blood returning to the heart after standing up, which leads to an abnormally fast heart rate. Palpitations and fainting can then occur.

Brain fog can be especially debilitating in people who are used to multitasking. With brain fog, people accustomed to easily alternating between tasks or doing multiple tasks at once can only do one thing at a time. This can cause stress and an overload of thoughts, even precipitating a change in careers if severe enough.

Though brain fog tends to resolve within 6-9 months after infection, it can last up to 18 months or more. Experts say doctors should always be on the lookout if a patient complains they have trouble concentrating or multitasking in the months after a COVID infection. A neurological exam and cognitive testing can identify abnormalities in brain function.

 

Subtype 4

About 40% of people in the study grouped into subtype 4 reported a poor or fair quality of life, a modest increase from those with subtype 3. About 65% reported symptoms of brain fog and 92% reported palpitations.

Dizziness was also prevalent at 71%, whereas 60% reported gastrointestinal issues, and 36% said they experienced fever, sweats, and chills.

Nearly 700 of the 2213 people fell into this subtype group, by far the highest number.

 

Subtype 5

A whopping 66% of people in subtype 5 reported a poor to fair quality of life. These people usually reported multisystem symptoms.

In terms of prevalence rises across the spectrum of 44 common long-COVID symptoms, 99% reported shortness of breath; 98%, postexertional soreness; 94%, dizziness; 92%, postexertional malaise; 80%, GI problems; 78%, weakness; and 69%, chest pain.

A higher proportion of Hispanic and multiracial participants were classified as having subtype 5. Also, according to the study, “higher proportions of unvaccinated participants and those with SARS-CoV-2 infection before circulation of the Omicron variant were in subtype 5.”

This suggests the severity of the Delta variant of COVID-19 be linked to some of the worst long COVID symptoms, but further study would have to be done to conclusively determine may be just a correlation.

 

When Do Symptoms Resolve?

According to Sanders, around 17 million Americans are thought to have long COVID. Although 90%-100% of people typically recover within 3 years, that still leaves possibly around 5% of those who don’t recover.

“What people usually say is, ‘I got COVID, and I never quite recovered,” Sanders said.

“Five percent of 17 million turns out to be a lot. It’s a lot of suffering,” she added. “I would say that the most common symptoms are fatigue, brain fog, anosmia or dysgeusia, and sleep disorders,” as evidenced by the high percentage of people in certain subtypes of the study reporting a poor quality of life.

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

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