Federal Practitioner

US Department of Veterans Affairs (VA) officials are insisting that when remote telehealth clinicians return to an office setting, they must have private workspaces “that foster trusted, confidential, and therapeutic relationships with veterans,” according to an April internal memo reported on by NPR. 

The return-to-office mandate followed a Trump Administration executive order in February indicated that mental health clinicians at the US Department of Veterans Affairs (VA) must physically return to their workplace by May 5. For some, the deadline came as early as April 14; however, that order, like many others, may now be being revised or reconsidered due to concerns that have been raised. Many mental health clinicians were hired specifically to work remotely. They worried there would simply not be enough space for them, particularly to provide confidential counseling.

Millions of veterans use telehealth to access VA care. More than 98% of VA mental health clinicians have conducted ≥ 1 video visit to screen and treat patients for anxiety, depression, posttraumatic stress disorder, and more. Telehealth has been particularly important for veterans living in rural communities.

The April VA memo stipulated that “spaces used to deliver synchronous telehealth services should offer the same level of privacy and therapeutic environment applicable to an in-person visit in the same space.”

Therapists, patients, advocacy groups, and lawmakers have expressed concern about the potential impacts the policy change could have on patient care for veterans and, above all, about what it could mean for privacy. On Mar. 27, the American Psychological Association issued a statement noting that the change “resulted in providers being asked to conduct sensitive therapy sessions in open office environments, cubicles, or shared spaces that fail to meet basic confidentiality and privacy requirements for the delivery of mental health care services.”

Twenty Democrats in the House of Representatives sent a letter to VA Secretary Doug Collins expressing concern with the return to office policy. According to the letter a VA social worker supervisor reported managing their caseload while sharing a 100 ft² shower space with another supervisor. It also reported that Clinical Resource Hub employees were being told to report to buildings where federal employees from other agencies work. “We have heard from countless stakeholders, veterans, and Department of Veterans Affairs (VA) employees that by carrying out President Trump’s blanket return-to-office policy your administration is damaging veteran and employee trust in VA, disrupting and impeding veterans’ access to care, and creating untenable and inefficient conditions for both veterans and the VA workforce,” the letter stated.

“This is a clear violation of veterans’ privacy and VA’s obligation to protect veterans’ private health information, and risks violation of the Health Insurance Portability and Accountability Act (HIPAA),” the letter added.

The lawmakers noted that, as of March 10, the VA was exempting Veterans Crisis Line workers, most of whom had been working remotely for the past 5 years, responding to more than 10 million calls, texts, and chats. That move, they said, indicated “that you understand there will be negative impacts to veterans’ care due to the return-to-office order and that these must be mitigated.”

VA spokesperson Peter Kasperowicz called the privacy concerns “nonsensical” and blamed “fear mongering from the media.” The VA, he said, “is no longer a place where the status quo for employees is to simply phone it in from home.” He also claimed that “the small number of employees who are desperate to avoid returning to the office will do more to drive away staff and patients than VA’s commonsense return-to-office policy ever will.”

VA care, he said, would continue uninterrupted and the “VA will ensure that employees have a workspace that is appropriate for the work they do.”

US Department of Veterans Affairs (VA) officials are insisting that when remote telehealth clinicians return to an office setting, they must have private workspaces “that foster trusted, confidential, and therapeutic relationships with veterans,” according to an April internal memo reported on by NPR. 

The return-to-office mandate followed a Trump Administration executive order in February indicated that mental health clinicians at the US Department of Veterans Affairs (VA) must physically return to their workplace by May 5. For some, the deadline came as early as April 14; however, that order, like many others, may now be being revised or reconsidered due to concerns that have been raised. Many mental health clinicians were hired specifically to work remotely. They worried there would simply not be enough space for them, particularly to provide confidential counseling.

Millions of veterans use telehealth to access VA care. More than 98% of VA mental health clinicians have conducted ≥ 1 video visit to screen and treat patients for anxiety, depression, posttraumatic stress disorder, and more. Telehealth has been particularly important for veterans living in rural communities.

The April VA memo stipulated that “spaces used to deliver synchronous telehealth services should offer the same level of privacy and therapeutic environment applicable to an in-person visit in the same space.”

Therapists, patients, advocacy groups, and lawmakers have expressed concern about the potential impacts the policy change could have on patient care for veterans and, above all, about what it could mean for privacy. On Mar. 27, the American Psychological Association issued a statement noting that the change “resulted in providers being asked to conduct sensitive therapy sessions in open office environments, cubicles, or shared spaces that fail to meet basic confidentiality and privacy requirements for the delivery of mental health care services.”

Twenty Democrats in the House of Representatives sent a letter to VA Secretary Doug Collins expressing concern with the return to office policy. According to the letter a VA social worker supervisor reported managing their caseload while sharing a 100 ft² shower space with another supervisor. It also reported that Clinical Resource Hub employees were being told to report to buildings where federal employees from other agencies work. “We have heard from countless stakeholders, veterans, and Department of Veterans Affairs (VA) employees that by carrying out President Trump’s blanket return-to-office policy your administration is damaging veteran and employee trust in VA, disrupting and impeding veterans’ access to care, and creating untenable and inefficient conditions for both veterans and the VA workforce,” the letter stated.

“This is a clear violation of veterans’ privacy and VA’s obligation to protect veterans’ private health information, and risks violation of the Health Insurance Portability and Accountability Act (HIPAA),” the letter added.

The lawmakers noted that, as of March 10, the VA was exempting Veterans Crisis Line workers, most of whom had been working remotely for the past 5 years, responding to more than 10 million calls, texts, and chats. That move, they said, indicated “that you understand there will be negative impacts to veterans’ care due to the return-to-office order and that these must be mitigated.”

VA spokesperson Peter Kasperowicz called the privacy concerns “nonsensical” and blamed “fear mongering from the media.” The VA, he said, “is no longer a place where the status quo for employees is to simply phone it in from home.” He also claimed that “the small number of employees who are desperate to avoid returning to the office will do more to drive away staff and patients than VA’s commonsense return-to-office policy ever will.”

VA care, he said, would continue uninterrupted and the “VA will ensure that employees have a workspace that is appropriate for the work they do.”

US Department of Veterans Affairs (VA) officials are insisting that when remote telehealth clinicians return to an office setting, they must have private workspaces “that foster trusted, confidential, and therapeutic relationships with veterans,” according to an April internal memo reported on by NPR. 

The return-to-office mandate followed a Trump Administration executive order in February indicated that mental health clinicians at the US Department of Veterans Affairs (VA) must physically return to their workplace by May 5. For some, the deadline came as early as April 14; however, that order, like many others, may now be being revised or reconsidered due to concerns that have been raised. Many mental health clinicians were hired specifically to work remotely. They worried there would simply not be enough space for them, particularly to provide confidential counseling.

Millions of veterans use telehealth to access VA care. More than 98% of VA mental health clinicians have conducted ≥ 1 video visit to screen and treat patients for anxiety, depression, posttraumatic stress disorder, and more. Telehealth has been particularly important for veterans living in rural communities.

The April VA memo stipulated that “spaces used to deliver synchronous telehealth services should offer the same level of privacy and therapeutic environment applicable to an in-person visit in the same space.”

Therapists, patients, advocacy groups, and lawmakers have expressed concern about the potential impacts the policy change could have on patient care for veterans and, above all, about what it could mean for privacy. On Mar. 27, the American Psychological Association issued a statement noting that the change “resulted in providers being asked to conduct sensitive therapy sessions in open office environments, cubicles, or shared spaces that fail to meet basic confidentiality and privacy requirements for the delivery of mental health care services.”

Twenty Democrats in the House of Representatives sent a letter to VA Secretary Doug Collins expressing concern with the return to office policy. According to the letter a VA social worker supervisor reported managing their caseload while sharing a 100 ft² shower space with another supervisor. It also reported that Clinical Resource Hub employees were being told to report to buildings where federal employees from other agencies work. “We have heard from countless stakeholders, veterans, and Department of Veterans Affairs (VA) employees that by carrying out President Trump’s blanket return-to-office policy your administration is damaging veteran and employee trust in VA, disrupting and impeding veterans’ access to care, and creating untenable and inefficient conditions for both veterans and the VA workforce,” the letter stated.

“This is a clear violation of veterans’ privacy and VA’s obligation to protect veterans’ private health information, and risks violation of the Health Insurance Portability and Accountability Act (HIPAA),” the letter added.

The lawmakers noted that, as of March 10, the VA was exempting Veterans Crisis Line workers, most of whom had been working remotely for the past 5 years, responding to more than 10 million calls, texts, and chats. That move, they said, indicated “that you understand there will be negative impacts to veterans’ care due to the return-to-office order and that these must be mitigated.”

VA spokesperson Peter Kasperowicz called the privacy concerns “nonsensical” and blamed “fear mongering from the media.” The VA, he said, “is no longer a place where the status quo for employees is to simply phone it in from home.” He also claimed that “the small number of employees who are desperate to avoid returning to the office will do more to drive away staff and patients than VA’s commonsense return-to-office policy ever will.”

VA care, he said, would continue uninterrupted and the “VA will ensure that employees have a workspace that is appropriate for the work they do.”

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.¹ Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. ² Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.^3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.^5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.^5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).⁸ Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A_1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.⁹ With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.¹⁰ Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.^11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.¹ Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. ² Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.^3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.^5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.^5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).⁸ Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A_1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.⁹ With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.¹⁰ Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.^11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.¹ Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. ² Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.^3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.^5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.^5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).⁸ Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A_1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.⁹ With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.¹⁰ Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.^11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

Since Lyme disease (LD) was first identified in 1975, there has been uncertainty regarding the proper diagnostic testing for suspected cases.¹ Challenges involved with ordering Lyme serology testing include navigating tests with an array of false negatives and false positives.² Confounding these challenges is the wide variety of ocular manifestations of LD, ranging from nonspecific conjunctivitis, cranial palsies, and anterior and posterior segment inflammation.^2,3 This article provides diagnostic testing guidelines for eye care clinicians who encounter patients with suspected LD.

BACKGROUND

LD is a bacterial infection caused by the spirochete Borrelia burgdorferi sensu lato complex transmitted by the Ixodes tick genus. There are 4 species of Ixodes ticks that can infect humans, and only 2 have been identified as principal vectors in North America: Ixodes scapularis and Ixodes pacificus. The incidence of LD is on the rise due to increasing global temperatures and expanding geographic borders for the organism. Cases in endemic areas range from 10 per 100,000 people to 50 per 100,000 people.⁴

LD occurs in 3 stages: early localized (stage 1), early disseminated (stage 2), and late disseminated (stage 3). In stage 1, patients typically present with erythema migrans (EM) rash (bull’s-eye cutaneous rash) and other nonspecific flu-like symptoms of fever, fatigue, and arthralgia. Stage 2 occurs several weeks to months after the initial infection and the infection has invaded other systemic organs, causing conditions like carditis, meningitis, and arthritis. A small subset of patients may progress to stage 3, which is characterized by chronic arthritis and chronic neurological LD.^2,4,5 Ocular manifestations have been well-documented in all stages of LD but are more prevalent in early disseminated disease (Table).^2,3,6,7

Indications

Recognizing common ocular manifestations associated with LD will allow eye care practitioners to make a timely diagnosis and initiate treatment. The most common ocular findings from LD include conjunctivitis, keratitis, cranial nerve VII palsy, optic neuritis, granulomatous iridocyclitis, and pars planitis.^2,6 While retrospective studies suggest that up to 10% of patients with early localized LD have a nonspecific follicular conjunctivitis, those patients are unlikely to present for ocular evaluation. If a patient does present with an acute conjunctivitis, many clinicians do not consider LD in their differential diagnosis.⁸ In endemic areas, it is important to query patients for additional symptoms that may indicate LD.

Obtaining a complete patient history is vital in aiding a clinician’s decision to order Lyme serology for suspected LD. Epidemiology, history of geography/travel, pet exposure, sexual history (necessary to rule out other conditions [ie, syphilis] to direct appropriate diagnostic testing), and a complete review of systems should be obtained.^2,4 LD may mimic other inflammatory autoimmune conditions or infectious diseases such as syphilis.^2,5 This can lead to obtaining unnecessary Lyme serologies or failing to diagnose LD.^5,7

Diagnostic testing is not indicated when a patient presents with an asymptomatic tick bite (ie, has no fever, malaise, or EM rash) or if a patient does not live in or has not recently traveled to an endemic area because it would be highly unlikely the patient has LD.^9,10 If the patient reports known contact with a tick and has a rash suspicious for EM, the diagnosis may be made without confirmatory testing because EM is pathognomonic for LD.^7,11 Serologic testing is not recommended in these cases, particularly if there is a single EM lesion, since the lesion often presents prior to development of an immune response leading to seronegative results.⁸

Lyme serology is necessary if a patient presents with ocular manifestations known to be associated with LD and resides in, or has recently traveled to, an area where LD is endemic (ie, New England, Minnesota, or Wisconsin).^7,12 These criteria are of particular importance: about 50% of patients do not recall a tick bite and 20% to 40% do not present with an EM.^2,9

Diagnostic Testing

In 2019 the Centers for Disease Control and Prevention (CDC) updated their testing guidelines to the modified 2-tier testing (MTTT) method. The MTTT first recommends a Lyme enzyme immunoassay (EIA), with a second EIA recommended only if the first is positive.^12-14 The MTTT method has better sensitivity in early localized LD compared to standard 2-tier testing.^9,11,12 The CDC advises against the use of any laboratory serology tests not approved by the US Food and Drug Administration.¹³ The CDC also advises that LD serology testing should not be performed as a “test for cure,” because even after successful treatment, an individual may still test positive.^1,9 Follow-up testing in patients treated early in the disease course (ie, in the setting of EM) may never have an antibody response. In these cases, a negative test should not exclude an LD diagnosis. ⁹ For patients with suspected neuroborreliosis, a lumbar puncture may not be needed if a patient already has a positive peripheral serology via the MTTT method.¹² The Figure depicts a flow chart for the process of ordering and interpreting testing.

Most LD testing, if correlated with clinical disease, is positive after 4 to 6 weeks.⁹ If an eye disease is noted and the patient has positive Lyme serology, the patient should still be screened for Lyme neuroborreliosis of the central nervous system (CNS). Examination of the fundus for papilledema, review of symptoms of aseptic meningitis, and a careful neurologic examination should be performed.¹⁵

If CNS disease is suspected, the patient may need additional CNS testing to support treatment decisions. The 2020 Infectious Diseases Society of America Lyme guidelines recommend to: (1) obtain simultaneous samples of cerebrospinal fluid (CSF) and serum for determination of the CSF:serum antibody index; (2) do not obtain CSF serology without measurement of the CSF:serum antibody index; and (3) do not obtain routine polymerase chain reaction or culture of CSF or serum.15 Once an LD diagnosis is confirmed, the CDC recommends a course of 100 mg of oral doxycycline twice daily for 14 to 21 days or an antimicrobial equivalent (eg, amoxicillin) if doxycycline is contraindicated. However, the antimicrobial dosage may vary depending on the stage of LD.¹¹ Patients with confirmed neuroborreliosis should be admitted for 14 days of intravenous ceftriaxone or intravenous penicillin.²

CONCLUSIONS

To ensure timely diagnosis and treatment, eye care clinicians should be familiar with the appropriate diagnostic testing for patients suspected to have ocular manifestations of LD. For patients with suspected LD and a high pretest probability, clinicians should obtain a first-order Lyme EIA.^12-14 If testing confirms LD, refer the patient to an infectious disease specialist for antimicrobial treatment and additional management.¹¹

Since Lyme disease (LD) was first identified in 1975, there has been uncertainty regarding the proper diagnostic testing for suspected cases.¹ Challenges involved with ordering Lyme serology testing include navigating tests with an array of false negatives and false positives.² Confounding these challenges is the wide variety of ocular manifestations of LD, ranging from nonspecific conjunctivitis, cranial palsies, and anterior and posterior segment inflammation.^2,3 This article provides diagnostic testing guidelines for eye care clinicians who encounter patients with suspected LD.

BACKGROUND

LD is a bacterial infection caused by the spirochete Borrelia burgdorferi sensu lato complex transmitted by the Ixodes tick genus. There are 4 species of Ixodes ticks that can infect humans, and only 2 have been identified as principal vectors in North America: Ixodes scapularis and Ixodes pacificus. The incidence of LD is on the rise due to increasing global temperatures and expanding geographic borders for the organism. Cases in endemic areas range from 10 per 100,000 people to 50 per 100,000 people.⁴

LD occurs in 3 stages: early localized (stage 1), early disseminated (stage 2), and late disseminated (stage 3). In stage 1, patients typically present with erythema migrans (EM) rash (bull’s-eye cutaneous rash) and other nonspecific flu-like symptoms of fever, fatigue, and arthralgia. Stage 2 occurs several weeks to months after the initial infection and the infection has invaded other systemic organs, causing conditions like carditis, meningitis, and arthritis. A small subset of patients may progress to stage 3, which is characterized by chronic arthritis and chronic neurological LD.^2,4,5 Ocular manifestations have been well-documented in all stages of LD but are more prevalent in early disseminated disease (Table).^2,3,6,7

Indications

Recognizing common ocular manifestations associated with LD will allow eye care practitioners to make a timely diagnosis and initiate treatment. The most common ocular findings from LD include conjunctivitis, keratitis, cranial nerve VII palsy, optic neuritis, granulomatous iridocyclitis, and pars planitis.^2,6 While retrospective studies suggest that up to 10% of patients with early localized LD have a nonspecific follicular conjunctivitis, those patients are unlikely to present for ocular evaluation. If a patient does present with an acute conjunctivitis, many clinicians do not consider LD in their differential diagnosis.⁸ In endemic areas, it is important to query patients for additional symptoms that may indicate LD.

Obtaining a complete patient history is vital in aiding a clinician’s decision to order Lyme serology for suspected LD. Epidemiology, history of geography/travel, pet exposure, sexual history (necessary to rule out other conditions [ie, syphilis] to direct appropriate diagnostic testing), and a complete review of systems should be obtained.^2,4 LD may mimic other inflammatory autoimmune conditions or infectious diseases such as syphilis.^2,5 This can lead to obtaining unnecessary Lyme serologies or failing to diagnose LD.^5,7

Diagnostic testing is not indicated when a patient presents with an asymptomatic tick bite (ie, has no fever, malaise, or EM rash) or if a patient does not live in or has not recently traveled to an endemic area because it would be highly unlikely the patient has LD.^9,10 If the patient reports known contact with a tick and has a rash suspicious for EM, the diagnosis may be made without confirmatory testing because EM is pathognomonic for LD.^7,11 Serologic testing is not recommended in these cases, particularly if there is a single EM lesion, since the lesion often presents prior to development of an immune response leading to seronegative results.⁸

Lyme serology is necessary if a patient presents with ocular manifestations known to be associated with LD and resides in, or has recently traveled to, an area where LD is endemic (ie, New England, Minnesota, or Wisconsin).^7,12 These criteria are of particular importance: about 50% of patients do not recall a tick bite and 20% to 40% do not present with an EM.^2,9

Diagnostic Testing

In 2019 the Centers for Disease Control and Prevention (CDC) updated their testing guidelines to the modified 2-tier testing (MTTT) method. The MTTT first recommends a Lyme enzyme immunoassay (EIA), with a second EIA recommended only if the first is positive.^12-14 The MTTT method has better sensitivity in early localized LD compared to standard 2-tier testing.^9,11,12 The CDC advises against the use of any laboratory serology tests not approved by the US Food and Drug Administration.¹³ The CDC also advises that LD serology testing should not be performed as a “test for cure,” because even after successful treatment, an individual may still test positive.^1,9 Follow-up testing in patients treated early in the disease course (ie, in the setting of EM) may never have an antibody response. In these cases, a negative test should not exclude an LD diagnosis. ⁹ For patients with suspected neuroborreliosis, a lumbar puncture may not be needed if a patient already has a positive peripheral serology via the MTTT method.¹² The Figure depicts a flow chart for the process of ordering and interpreting testing.

Most LD testing, if correlated with clinical disease, is positive after 4 to 6 weeks.⁹ If an eye disease is noted and the patient has positive Lyme serology, the patient should still be screened for Lyme neuroborreliosis of the central nervous system (CNS). Examination of the fundus for papilledema, review of symptoms of aseptic meningitis, and a careful neurologic examination should be performed.¹⁵

If CNS disease is suspected, the patient may need additional CNS testing to support treatment decisions. The 2020 Infectious Diseases Society of America Lyme guidelines recommend to: (1) obtain simultaneous samples of cerebrospinal fluid (CSF) and serum for determination of the CSF:serum antibody index; (2) do not obtain CSF serology without measurement of the CSF:serum antibody index; and (3) do not obtain routine polymerase chain reaction or culture of CSF or serum.15 Once an LD diagnosis is confirmed, the CDC recommends a course of 100 mg of oral doxycycline twice daily for 14 to 21 days or an antimicrobial equivalent (eg, amoxicillin) if doxycycline is contraindicated. However, the antimicrobial dosage may vary depending on the stage of LD.¹¹ Patients with confirmed neuroborreliosis should be admitted for 14 days of intravenous ceftriaxone or intravenous penicillin.²

CONCLUSIONS

To ensure timely diagnosis and treatment, eye care clinicians should be familiar with the appropriate diagnostic testing for patients suspected to have ocular manifestations of LD. For patients with suspected LD and a high pretest probability, clinicians should obtain a first-order Lyme EIA.^12-14 If testing confirms LD, refer the patient to an infectious disease specialist for antimicrobial treatment and additional management.¹¹

Since Lyme disease (LD) was first identified in 1975, there has been uncertainty regarding the proper diagnostic testing for suspected cases.¹ Challenges involved with ordering Lyme serology testing include navigating tests with an array of false negatives and false positives.² Confounding these challenges is the wide variety of ocular manifestations of LD, ranging from nonspecific conjunctivitis, cranial palsies, and anterior and posterior segment inflammation.^2,3 This article provides diagnostic testing guidelines for eye care clinicians who encounter patients with suspected LD.

BACKGROUND

LD is a bacterial infection caused by the spirochete Borrelia burgdorferi sensu lato complex transmitted by the Ixodes tick genus. There are 4 species of Ixodes ticks that can infect humans, and only 2 have been identified as principal vectors in North America: Ixodes scapularis and Ixodes pacificus. The incidence of LD is on the rise due to increasing global temperatures and expanding geographic borders for the organism. Cases in endemic areas range from 10 per 100,000 people to 50 per 100,000 people.⁴

LD occurs in 3 stages: early localized (stage 1), early disseminated (stage 2), and late disseminated (stage 3). In stage 1, patients typically present with erythema migrans (EM) rash (bull’s-eye cutaneous rash) and other nonspecific flu-like symptoms of fever, fatigue, and arthralgia. Stage 2 occurs several weeks to months after the initial infection and the infection has invaded other systemic organs, causing conditions like carditis, meningitis, and arthritis. A small subset of patients may progress to stage 3, which is characterized by chronic arthritis and chronic neurological LD.^2,4,5 Ocular manifestations have been well-documented in all stages of LD but are more prevalent in early disseminated disease (Table).^2,3,6,7

Indications

Recognizing common ocular manifestations associated with LD will allow eye care practitioners to make a timely diagnosis and initiate treatment. The most common ocular findings from LD include conjunctivitis, keratitis, cranial nerve VII palsy, optic neuritis, granulomatous iridocyclitis, and pars planitis.^2,6 While retrospective studies suggest that up to 10% of patients with early localized LD have a nonspecific follicular conjunctivitis, those patients are unlikely to present for ocular evaluation. If a patient does present with an acute conjunctivitis, many clinicians do not consider LD in their differential diagnosis.⁸ In endemic areas, it is important to query patients for additional symptoms that may indicate LD.

Obtaining a complete patient history is vital in aiding a clinician’s decision to order Lyme serology for suspected LD. Epidemiology, history of geography/travel, pet exposure, sexual history (necessary to rule out other conditions [ie, syphilis] to direct appropriate diagnostic testing), and a complete review of systems should be obtained.^2,4 LD may mimic other inflammatory autoimmune conditions or infectious diseases such as syphilis.^2,5 This can lead to obtaining unnecessary Lyme serologies or failing to diagnose LD.^5,7

Diagnostic testing is not indicated when a patient presents with an asymptomatic tick bite (ie, has no fever, malaise, or EM rash) or if a patient does not live in or has not recently traveled to an endemic area because it would be highly unlikely the patient has LD.^9,10 If the patient reports known contact with a tick and has a rash suspicious for EM, the diagnosis may be made without confirmatory testing because EM is pathognomonic for LD.^7,11 Serologic testing is not recommended in these cases, particularly if there is a single EM lesion, since the lesion often presents prior to development of an immune response leading to seronegative results.⁸

Lyme serology is necessary if a patient presents with ocular manifestations known to be associated with LD and resides in, or has recently traveled to, an area where LD is endemic (ie, New England, Minnesota, or Wisconsin).^7,12 These criteria are of particular importance: about 50% of patients do not recall a tick bite and 20% to 40% do not present with an EM.^2,9

Diagnostic Testing

In 2019 the Centers for Disease Control and Prevention (CDC) updated their testing guidelines to the modified 2-tier testing (MTTT) method. The MTTT first recommends a Lyme enzyme immunoassay (EIA), with a second EIA recommended only if the first is positive.^12-14 The MTTT method has better sensitivity in early localized LD compared to standard 2-tier testing.^9,11,12 The CDC advises against the use of any laboratory serology tests not approved by the US Food and Drug Administration.¹³ The CDC also advises that LD serology testing should not be performed as a “test for cure,” because even after successful treatment, an individual may still test positive.^1,9 Follow-up testing in patients treated early in the disease course (ie, in the setting of EM) may never have an antibody response. In these cases, a negative test should not exclude an LD diagnosis. ⁹ For patients with suspected neuroborreliosis, a lumbar puncture may not be needed if a patient already has a positive peripheral serology via the MTTT method.¹² The Figure depicts a flow chart for the process of ordering and interpreting testing.

Most LD testing, if correlated with clinical disease, is positive after 4 to 6 weeks.⁹ If an eye disease is noted and the patient has positive Lyme serology, the patient should still be screened for Lyme neuroborreliosis of the central nervous system (CNS). Examination of the fundus for papilledema, review of symptoms of aseptic meningitis, and a careful neurologic examination should be performed.¹⁵

If CNS disease is suspected, the patient may need additional CNS testing to support treatment decisions. The 2020 Infectious Diseases Society of America Lyme guidelines recommend to: (1) obtain simultaneous samples of cerebrospinal fluid (CSF) and serum for determination of the CSF:serum antibody index; (2) do not obtain CSF serology without measurement of the CSF:serum antibody index; and (3) do not obtain routine polymerase chain reaction or culture of CSF or serum.15 Once an LD diagnosis is confirmed, the CDC recommends a course of 100 mg of oral doxycycline twice daily for 14 to 21 days or an antimicrobial equivalent (eg, amoxicillin) if doxycycline is contraindicated. However, the antimicrobial dosage may vary depending on the stage of LD.¹¹ Patients with confirmed neuroborreliosis should be admitted for 14 days of intravenous ceftriaxone or intravenous penicillin.²

CONCLUSIONS

To ensure timely diagnosis and treatment, eye care clinicians should be familiar with the appropriate diagnostic testing for patients suspected to have ocular manifestations of LD. For patients with suspected LD and a high pretest probability, clinicians should obtain a first-order Lyme EIA.^12-14 If testing confirms LD, refer the patient to an infectious disease specialist for antimicrobial treatment and additional management.¹¹

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships

SAN DIEGO — Not surprisingly, the contraception clinic at Madigan Army Medical Center near Tacoma, Wash., is popular among female soldiers seeking to avoid pregnancy. However, about half of the patients drop by for other reasons, the military pharmacist who runs the program told colleagues here at the Joint Federal Pharmacy Seminar.
“They come to suppress menstruation, to get help with pain, to get help with PCOS [polycystic ovary syndrome] symptoms. They're coming for a wide range of indications that we use contraception to treat,” said Sarah Abel, PharmD, a clinical pharmacist. 

Regardless of the reason, Abel emphasized that contraceptives can significantly impact the ability of female soldiers to do their jobs.  “If you have heavy periods and can't make it in work, or you have endometriosis and  requiring a lot of doctor's appointments, or you're deployed and you get pregnant, these are all situations where contraceptive care matters,” she said. Rates of unintended pregnancy are higher in servicewomen than in the general population.
Abel, who opened the medical center’s contraceptive clinic about 10 years ago, stressed that it’s crucial to military readiness considering that the percentage of women in the American military is approaching 20%. 

Thanks to a 2022 edict, military hospitals and clinics are required to offer walk-in contraceptive services with same-day access, no requirements for appointments or referrals. An announcement about the mandate noted that these contraceptive services, such as preventing unplanned pregnancy and decreasing menstrual periods, “support the overall well-being of the force and optimize personal warrior readiness.”

As Abel noted, 29 states and Washington D.C. allow pharmacists to prescribe contraception to outpatients, although the requirements vary. “Can we start practicing at the top of our license and start prescribing in the outpatient setting? Absolutely we should,” she said. “Pharmacists have a very unique opportunity to be a part of this.”

Abel also shared that setting up a contraceptive program requires patience and education. “I cannot tell you how many women have come to me who don't know the different names of their body parts, women who've had two babies that don't understand how their body works. So, I constantly find myself taking extra time to do general sexual education,” she said.

There are many lessons to impart to patients about sexual health. For example, birth control drugs and devices do not prevent transmission of sexually transmitted infections (STIs). “So I have bowls of condoms literally everywhere because condoms are the only thing that protects against STIs,” Abel said.

In terms of devices, “we have diaphragms available and cervical caps,” she said. “The Caya diaphragm is a TRICARE-covered benefit. It’s a small purple diaphragm, one size fits most. We can prescribe it, and it is good for 2 years. Unfortunately, spermicide, which you have to use with these things, is not a TRICARE-covered benefit.”
Hormonal contraceptives are also available, with Abel recommending the continuous monophasic type for most women. “Please don't tell women they have to have their periods. They don't,” she said. “What I'm trying to do is give a woman some stability in her hormones. She can know and expect what she's going to feel like. She's not going to wake up and say, ‘Oh God, today's the day. I'm going to be like this for a week.’”

Patches are another option, and a flurry of patients have been asking about them because of recent TikTok videos promoting their use. “We have the Xulane patch, our bread and butter. They wear it on their shoulder, their hip, their butt, or their back. They leave it in place for a week at a time. And every week, they will change that patch. I usually have to walk patients through a whole month to help them understand how that works.”

Another option, the NuvaRing, is notable because it’s linked to low amounts of breakthrough bleeding Abel noted. An extended form is now available that doesn’t need to be removed during menstrual periods.

Medroxyprogesterone injections, which are linked to bone loss, and subdermal implants, which may be less effective in women over 130% of their ideal weight are also available, she said. 

Finally, IUDs are an option, although when they fail, they’re linked to ectopic pregnancies.   

Abel has no disclosures.  

SAN DIEGO — Not surprisingly, the contraception clinic at Madigan Army Medical Center near Tacoma, Wash., is popular among female soldiers seeking to avoid pregnancy. However, about half of the patients drop by for other reasons, the military pharmacist who runs the program told colleagues here at the Joint Federal Pharmacy Seminar.
“They come to suppress menstruation, to get help with pain, to get help with PCOS [polycystic ovary syndrome] symptoms. They're coming for a wide range of indications that we use contraception to treat,” said Sarah Abel, PharmD, a clinical pharmacist. 

Regardless of the reason, Abel emphasized that contraceptives can significantly impact the ability of female soldiers to do their jobs.  “If you have heavy periods and can't make it in work, or you have endometriosis and  requiring a lot of doctor's appointments, or you're deployed and you get pregnant, these are all situations where contraceptive care matters,” she said. Rates of unintended pregnancy are higher in servicewomen than in the general population.
Abel, who opened the medical center’s contraceptive clinic about 10 years ago, stressed that it’s crucial to military readiness considering that the percentage of women in the American military is approaching 20%. 

Thanks to a 2022 edict, military hospitals and clinics are required to offer walk-in contraceptive services with same-day access, no requirements for appointments or referrals. An announcement about the mandate noted that these contraceptive services, such as preventing unplanned pregnancy and decreasing menstrual periods, “support the overall well-being of the force and optimize personal warrior readiness.”

As Abel noted, 29 states and Washington D.C. allow pharmacists to prescribe contraception to outpatients, although the requirements vary. “Can we start practicing at the top of our license and start prescribing in the outpatient setting? Absolutely we should,” she said. “Pharmacists have a very unique opportunity to be a part of this.”

Abel also shared that setting up a contraceptive program requires patience and education. “I cannot tell you how many women have come to me who don't know the different names of their body parts, women who've had two babies that don't understand how their body works. So, I constantly find myself taking extra time to do general sexual education,” she said.

There are many lessons to impart to patients about sexual health. For example, birth control drugs and devices do not prevent transmission of sexually transmitted infections (STIs). “So I have bowls of condoms literally everywhere because condoms are the only thing that protects against STIs,” Abel said.

In terms of devices, “we have diaphragms available and cervical caps,” she said. “The Caya diaphragm is a TRICARE-covered benefit. It’s a small purple diaphragm, one size fits most. We can prescribe it, and it is good for 2 years. Unfortunately, spermicide, which you have to use with these things, is not a TRICARE-covered benefit.”
Hormonal contraceptives are also available, with Abel recommending the continuous monophasic type for most women. “Please don't tell women they have to have their periods. They don't,” she said. “What I'm trying to do is give a woman some stability in her hormones. She can know and expect what she's going to feel like. She's not going to wake up and say, ‘Oh God, today's the day. I'm going to be like this for a week.’”

Patches are another option, and a flurry of patients have been asking about them because of recent TikTok videos promoting their use. “We have the Xulane patch, our bread and butter. They wear it on their shoulder, their hip, their butt, or their back. They leave it in place for a week at a time. And every week, they will change that patch. I usually have to walk patients through a whole month to help them understand how that works.”

Another option, the NuvaRing, is notable because it’s linked to low amounts of breakthrough bleeding Abel noted. An extended form is now available that doesn’t need to be removed during menstrual periods.

Medroxyprogesterone injections, which are linked to bone loss, and subdermal implants, which may be less effective in women over 130% of their ideal weight are also available, she said. 

Finally, IUDs are an option, although when they fail, they’re linked to ectopic pregnancies.   

Abel has no disclosures.  

SAN DIEGO — Not surprisingly, the contraception clinic at Madigan Army Medical Center near Tacoma, Wash., is popular among female soldiers seeking to avoid pregnancy. However, about half of the patients drop by for other reasons, the military pharmacist who runs the program told colleagues here at the Joint Federal Pharmacy Seminar.
“They come to suppress menstruation, to get help with pain, to get help with PCOS [polycystic ovary syndrome] symptoms. They're coming for a wide range of indications that we use contraception to treat,” said Sarah Abel, PharmD, a clinical pharmacist. 

Regardless of the reason, Abel emphasized that contraceptives can significantly impact the ability of female soldiers to do their jobs.  “If you have heavy periods and can't make it in work, or you have endometriosis and  requiring a lot of doctor's appointments, or you're deployed and you get pregnant, these are all situations where contraceptive care matters,” she said. Rates of unintended pregnancy are higher in servicewomen than in the general population.
Abel, who opened the medical center’s contraceptive clinic about 10 years ago, stressed that it’s crucial to military readiness considering that the percentage of women in the American military is approaching 20%. 

Thanks to a 2022 edict, military hospitals and clinics are required to offer walk-in contraceptive services with same-day access, no requirements for appointments or referrals. An announcement about the mandate noted that these contraceptive services, such as preventing unplanned pregnancy and decreasing menstrual periods, “support the overall well-being of the force and optimize personal warrior readiness.”

As Abel noted, 29 states and Washington D.C. allow pharmacists to prescribe contraception to outpatients, although the requirements vary. “Can we start practicing at the top of our license and start prescribing in the outpatient setting? Absolutely we should,” she said. “Pharmacists have a very unique opportunity to be a part of this.”

Abel also shared that setting up a contraceptive program requires patience and education. “I cannot tell you how many women have come to me who don't know the different names of their body parts, women who've had two babies that don't understand how their body works. So, I constantly find myself taking extra time to do general sexual education,” she said.

There are many lessons to impart to patients about sexual health. For example, birth control drugs and devices do not prevent transmission of sexually transmitted infections (STIs). “So I have bowls of condoms literally everywhere because condoms are the only thing that protects against STIs,” Abel said.

In terms of devices, “we have diaphragms available and cervical caps,” she said. “The Caya diaphragm is a TRICARE-covered benefit. It’s a small purple diaphragm, one size fits most. We can prescribe it, and it is good for 2 years. Unfortunately, spermicide, which you have to use with these things, is not a TRICARE-covered benefit.”
Hormonal contraceptives are also available, with Abel recommending the continuous monophasic type for most women. “Please don't tell women they have to have their periods. They don't,” she said. “What I'm trying to do is give a woman some stability in her hormones. She can know and expect what she's going to feel like. She's not going to wake up and say, ‘Oh God, today's the day. I'm going to be like this for a week.’”

Patches are another option, and a flurry of patients have been asking about them because of recent TikTok videos promoting their use. “We have the Xulane patch, our bread and butter. They wear it on their shoulder, their hip, their butt, or their back. They leave it in place for a week at a time. And every week, they will change that patch. I usually have to walk patients through a whole month to help them understand how that works.”

Another option, the NuvaRing, is notable because it’s linked to low amounts of breakthrough bleeding Abel noted. An extended form is now available that doesn’t need to be removed during menstrual periods.

Medroxyprogesterone injections, which are linked to bone loss, and subdermal implants, which may be less effective in women over 130% of their ideal weight are also available, she said. 

Finally, IUDs are an option, although when they fail, they’re linked to ectopic pregnancies.   

Abel has no disclosures.