Recent natural disasters, civil disorder, and the COVID-19 pandemic response created an unprecedented demand for the US National Guard and Reserve components as well as active-duty personnel to serve on homefront missions critical to our nation. At times, those serving in these capacities are front and center to the most tragic events confronting our nation, and they frequently encounter tremendous suffering.

Recognizing the potential for these missions to create psychological sequela for those who serve on them, the authority for the Veterans Health Administration (VHA) vet centers to provide readjustment counseling services was broadened on December 30, 2021. Vet centers are community-based counseling centers that have traditionally served combat veterans, and broadening services reflects a major change in mission. Revised VHA Directive 1500(2) specifies that those who “served on active duty in response to a national emergency or major disaster declared by the President” or “served on active duty in the National Guard of a State under orders of the chief executive of that State in response to a disaster or civil disorder in such State” may now receive therapy at vet centers.^1,2

As a result of this recent policy change, National Guard and active-duty Reserve service members now have parity with combat veterans to obtain therapy for symptoms arising as a result of their activation for service on homefront missions. As they seek care, we need to be ready so that these service members can obtain the best therapy services possible. Soldiers who served on homefront missions comprise a new cohort of service members now eligible for vet center therapy. Soldiers who served on homefront missions may present with issues that differ from those of combat veterans and veterans who have experienced military sexual trauma (MST), the populations treated by vet centers and other VHA mental health care clinics prior to this broadened authority. This article highlights some suggestions for service delivery to best meet the needs of this population.

Discussion 

Available evidence-based therapies to treat posttraumatic stress disorder (PTSD) are effective regardless of whether the trauma occurred in combat, on the homefront, or in a civilian setting. The vet centers and VHA mental health services already have staff trained to deliver these therapy modalities and, in this sense, are ready to provide trauma-focused therapy treatment to soldiers with PTSD who served on homefront missions.

The broadened authority for the vet centers to provide readjustment services is necessary, as it corrects for a critical gap in services, but the importance of ensuring adequate staffing to meet the expected increased demand for services cannot be underscored. According to clinical practice guidelines for the treatment of PTSD, developed by the US Department of Veterans Affairs (VA) and the US Department of Defense (DoD), the therapies with the strongest evidence-based backing are prolonged exposure-based therapy (PE), cognitive processing therapy (CPT), and eye movement and desensitization reprocessing (EMDR).³ These therapy modalities, based on findings from clinical trials, are predicated on seeing a client for a sufficient number of sessions. Attendance at these sessions is recommended at least weekly to ensure adequate intensity of service delivery.^4-7 According to the National Center for PTSD, PE typically involves 8 to 15 weekly or twice weekly sessions; CPT requires 8 to 14 or more weekly sessions, and EMDR is usually 4 to 12 weekly sessions.^4-7

Ensuring adequate staffing is critical to offer these therapies at least weekly as the efficacies of these therapies are otherwise not proven if return session visits are stretched out over multiple weeks or months. The most recent clinical research has demonstrated that PTSD recovery can be expedited and there are lower patient dropout rates when sessions are massed or compressed so that multiple sessions are administered over 1 week.^8-12 Providing these therapies in a massed format has shown to be as effective as when these therapies are provided weekly.

As the authority to treat soldiers serving on homefront missions is new, epidemiologic data do not yet exist to estimate the proportion of this population who will need treatment or present with PTSD, depression, anxiety, a substance use disorder, and/or comorbid conditions. Those with PTSD can benefit from PTSD evidence-based therapies already available for treatment. Others may benefit from treatments that are proven effective for their mental health diagnoses.

Conclusions

Now that National Guard and Reserve component soldiers who have responded to national and local emergencies are eligible for therapy, we need to be prepared to provide these services. In addition to addressing systemic staffing concerns, therapists need to be aware of the unique challenges faced by those who have served on homefront missions. These homefront missions have the potential to hit home for therapists.

Recent natural disasters, civil disorder, and the COVID-19 pandemic response created an unprecedented demand for the US National Guard and Reserve components as well as active-duty personnel to serve on homefront missions critical to our nation. At times, those serving in these capacities are front and center to the most tragic events confronting our nation, and they frequently encounter tremendous suffering.

Recognizing the potential for these missions to create psychological sequela for those who serve on them, the authority for the Veterans Health Administration (VHA) vet centers to provide readjustment counseling services was broadened on December 30, 2021. Vet centers are community-based counseling centers that have traditionally served combat veterans, and broadening services reflects a major change in mission. Revised VHA Directive 1500(2) specifies that those who “served on active duty in response to a national emergency or major disaster declared by the President” or “served on active duty in the National Guard of a State under orders of the chief executive of that State in response to a disaster or civil disorder in such State” may now receive therapy at vet centers.^1,2

As a result of this recent policy change, National Guard and active-duty Reserve service members now have parity with combat veterans to obtain therapy for symptoms arising as a result of their activation for service on homefront missions. As they seek care, we need to be ready so that these service members can obtain the best therapy services possible. Soldiers who served on homefront missions comprise a new cohort of service members now eligible for vet center therapy. Soldiers who served on homefront missions may present with issues that differ from those of combat veterans and veterans who have experienced military sexual trauma (MST), the populations treated by vet centers and other VHA mental health care clinics prior to this broadened authority. This article highlights some suggestions for service delivery to best meet the needs of this population.

Discussion 

Available evidence-based therapies to treat posttraumatic stress disorder (PTSD) are effective regardless of whether the trauma occurred in combat, on the homefront, or in a civilian setting. The vet centers and VHA mental health services already have staff trained to deliver these therapy modalities and, in this sense, are ready to provide trauma-focused therapy treatment to soldiers with PTSD who served on homefront missions.

The broadened authority for the vet centers to provide readjustment services is necessary, as it corrects for a critical gap in services, but the importance of ensuring adequate staffing to meet the expected increased demand for services cannot be underscored. According to clinical practice guidelines for the treatment of PTSD, developed by the US Department of Veterans Affairs (VA) and the US Department of Defense (DoD), the therapies with the strongest evidence-based backing are prolonged exposure-based therapy (PE), cognitive processing therapy (CPT), and eye movement and desensitization reprocessing (EMDR).³ These therapy modalities, based on findings from clinical trials, are predicated on seeing a client for a sufficient number of sessions. Attendance at these sessions is recommended at least weekly to ensure adequate intensity of service delivery.^4-7 According to the National Center for PTSD, PE typically involves 8 to 15 weekly or twice weekly sessions; CPT requires 8 to 14 or more weekly sessions, and EMDR is usually 4 to 12 weekly sessions.^4-7

Ensuring adequate staffing is critical to offer these therapies at least weekly as the efficacies of these therapies are otherwise not proven if return session visits are stretched out over multiple weeks or months. The most recent clinical research has demonstrated that PTSD recovery can be expedited and there are lower patient dropout rates when sessions are massed or compressed so that multiple sessions are administered over 1 week.^8-12 Providing these therapies in a massed format has shown to be as effective as when these therapies are provided weekly.

As the authority to treat soldiers serving on homefront missions is new, epidemiologic data do not yet exist to estimate the proportion of this population who will need treatment or present with PTSD, depression, anxiety, a substance use disorder, and/or comorbid conditions. Those with PTSD can benefit from PTSD evidence-based therapies already available for treatment. Others may benefit from treatments that are proven effective for their mental health diagnoses.

Conclusions

Now that National Guard and Reserve component soldiers who have responded to national and local emergencies are eligible for therapy, we need to be prepared to provide these services. In addition to addressing systemic staffing concerns, therapists need to be aware of the unique challenges faced by those who have served on homefront missions. These homefront missions have the potential to hit home for therapists.

Recent natural disasters, civil disorder, and the COVID-19 pandemic response created an unprecedented demand for the US National Guard and Reserve components as well as active-duty personnel to serve on homefront missions critical to our nation. At times, those serving in these capacities are front and center to the most tragic events confronting our nation, and they frequently encounter tremendous suffering.

Recognizing the potential for these missions to create psychological sequela for those who serve on them, the authority for the Veterans Health Administration (VHA) vet centers to provide readjustment counseling services was broadened on December 30, 2021. Vet centers are community-based counseling centers that have traditionally served combat veterans, and broadening services reflects a major change in mission. Revised VHA Directive 1500(2) specifies that those who “served on active duty in response to a national emergency or major disaster declared by the President” or “served on active duty in the National Guard of a State under orders of the chief executive of that State in response to a disaster or civil disorder in such State” may now receive therapy at vet centers.^1,2

As a result of this recent policy change, National Guard and active-duty Reserve service members now have parity with combat veterans to obtain therapy for symptoms arising as a result of their activation for service on homefront missions. As they seek care, we need to be ready so that these service members can obtain the best therapy services possible. Soldiers who served on homefront missions comprise a new cohort of service members now eligible for vet center therapy. Soldiers who served on homefront missions may present with issues that differ from those of combat veterans and veterans who have experienced military sexual trauma (MST), the populations treated by vet centers and other VHA mental health care clinics prior to this broadened authority. This article highlights some suggestions for service delivery to best meet the needs of this population.

Discussion 

Available evidence-based therapies to treat posttraumatic stress disorder (PTSD) are effective regardless of whether the trauma occurred in combat, on the homefront, or in a civilian setting. The vet centers and VHA mental health services already have staff trained to deliver these therapy modalities and, in this sense, are ready to provide trauma-focused therapy treatment to soldiers with PTSD who served on homefront missions.

The broadened authority for the vet centers to provide readjustment services is necessary, as it corrects for a critical gap in services, but the importance of ensuring adequate staffing to meet the expected increased demand for services cannot be underscored. According to clinical practice guidelines for the treatment of PTSD, developed by the US Department of Veterans Affairs (VA) and the US Department of Defense (DoD), the therapies with the strongest evidence-based backing are prolonged exposure-based therapy (PE), cognitive processing therapy (CPT), and eye movement and desensitization reprocessing (EMDR).³ These therapy modalities, based on findings from clinical trials, are predicated on seeing a client for a sufficient number of sessions. Attendance at these sessions is recommended at least weekly to ensure adequate intensity of service delivery.^4-7 According to the National Center for PTSD, PE typically involves 8 to 15 weekly or twice weekly sessions; CPT requires 8 to 14 or more weekly sessions, and EMDR is usually 4 to 12 weekly sessions.^4-7

Ensuring adequate staffing is critical to offer these therapies at least weekly as the efficacies of these therapies are otherwise not proven if return session visits are stretched out over multiple weeks or months. The most recent clinical research has demonstrated that PTSD recovery can be expedited and there are lower patient dropout rates when sessions are massed or compressed so that multiple sessions are administered over 1 week.^8-12 Providing these therapies in a massed format has shown to be as effective as when these therapies are provided weekly.

As the authority to treat soldiers serving on homefront missions is new, epidemiologic data do not yet exist to estimate the proportion of this population who will need treatment or present with PTSD, depression, anxiety, a substance use disorder, and/or comorbid conditions. Those with PTSD can benefit from PTSD evidence-based therapies already available for treatment. Others may benefit from treatments that are proven effective for their mental health diagnoses.

Conclusions

Now that National Guard and Reserve component soldiers who have responded to national and local emergencies are eligible for therapy, we need to be prepared to provide these services. In addition to addressing systemic staffing concerns, therapists need to be aware of the unique challenges faced by those who have served on homefront missions. These homefront missions have the potential to hit home for therapists.

►Anish Bhatnagar, MD, Chief Medical Resident, Veterans Affairs Boston Healthcare System (VABHS) and Beth Israel Deaconess Medical Center (BIDMC): The patient noted erectile dysfunction starting 4 years ago, with accompanied decreased libido. However, until recently, he was able to achieve acceptable erectile capacity with medications. As part of his previous evaluations for erectile dysfunction, the patient had 2 total testosterone levels checked 6 months apart, both low at 150 ng/dL and 38.3 ng/dL (reference range, 220-892). The results of additional hormone studies are shown in the Table. Dr. Ananthakrishnan, can you help us interpret these laboratory results and tell us what tests you might order next?

►Sonia Ananthakrishnan, MD, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center (BMC) and Assistant Professor of Medicine, Boston University School of Medicine (BUSM): When patients present with signs of hypogonadism and an initial low morning testosterone levels, the next test should be a confirmatory repeat morning testosterone level as was done in this case. If this level is also low (for most assays < 300 ng/dL), further evaluation for primary vs secondary hypogonadism should be pursued with measurement of luteinizing hormone and follicle-stimulating hormone levels. Secondary hypogonadism should be suspected when these levels are low or inappropriately normal in the setting of a low testosterone level as in this patient. This patient does not appear to be on any medication or have reversible illnesses that we traditionally think of as possibly causing these hormone irregularities. Key examples include medications such as gonadotropin-releasing hormone analogs, glucocorticoids, and opioids, as well as conditions such as hyperprolactinemia, sleep apnea, diabetes mellitus, anorexia nervosa, or other chronic systemic illnesses, including cirrhosis or lung disease. In this setting, further evaluation of the patient’s anterior pituitary function should be undertaken. Initial screening tests showed mildly elevated prolactin and low normal thyroid-stimulating hormone levels, with a relatively normal free thyroxine. Given these abnormalities in the context of the patient’s total testosterone level < 150 ng/dL, magnetic resonance imaging (MRI) of the anterior pituitary is indicated, and what I would recommend next for evaluation of pituitary and/or hypothalamic tumor or infiltrative disease.¹

►Dr. Bhatnagar: An MRI of the brain showed a large 2.7-cm sellar mass, with suprasellar extension and mass effect on the optic chiasm and pituitary infundibulum, partial extension into the right sphenoid sinus, and invasion into the right cavernous sinus. These findings were consistent with a pituitary macroadenoma. The patient was subsequently evaluated by a neurosurgeon who felt that because of the extension and compression of the mass, the patient would benefit from surgical resection.

Given his lower urinary tract symptoms, a prostate-specific antigen level was checked and returned elevated at 11.5 ng/mL. In the setting of these abnormalities, the patient underwent MRI of the abdomen, which noted a new 5.6-cm enhancing mass in the upper pole of his solitary right kidney, highly concerning for new RCC. After a multidisciplinary discussion, urology scheduled the patient for partial right nephrectomy first, with plans for pituitary resection only if the patient had adequate recovery following the urologic procedure.

Dr. Rifkin, this patient went straight from imaging to presumed diagnosis to planned surgical intervention without a confirmatory biopsy. In a patient who already has chronic kidney disease stage 4, why would we not want to pursue biopsy prior to this invasive procedure on his solitary kidney? In addition, given his baseline advanced renal disease, why pursue partial nephrectomy to delay initiation of hemodialysis instead of total nephrectomy and beginning hemodialysis?

►Ian Rifkin, MBBCh, PhD, MSc, Chief, Renal Section, VABHS, Section of Nephrology, BMC, and Associate Professor of Medicine, BUSM: In most cases, imaging alone is used to make a presumptive diagnosis of benign vs malignant renal masses. In one study, RCC was identified by MRI with 85% sensitivity and 76% specificity.² However, as imaging and biopsy techniques have advanced, there are progressing discussions regarding the utility of biopsy. That being said, there are a number of situations in which patients currently undergo biopsy, particularly when there is diagnostic uncertainty.³ In this patient, with a history of RCC and imaging findings concerning for RCC, biopsy is unnecessary given the high clinical suspicion.

Regarding the choice of partial vs total nephrectomy, there are 2 important distinctions to be made. The first is that though it was previously felt that early initiation of dialysis improves survival, newer studies suggest that early initiation based off of glomerular filtration rate (GFR) offers no survival benefits compared to delayed initiation.⁴ Second, though there is less clinical data to support this, there is a signal toward the use of partial nephrectomy decreasing mortality compared to radical nephrectomy in management of RCC.⁵ In this patient, partial nephrectomy may not only increase rates of survival, but also delay initiation of dialysis.

►Dr. Bhatnagar: Prior to undergoing partial right nephrectomy, a morning cortisol level was found to be 5.8 μg/dL with an associated corticotropin (ACTH) level of 26 pg/mL. Dr. Ananthakrishnan, how would you interpret these laboratory results and what might you recommend prior to surgery?

►Dr. Bhatnagar: The patient was started on hydrocortisone and underwent a successful laparoscopic partial right nephrectomy. During the procedure, an estimated 2.5 L of blood was lost, with transfusion of 3 units of packed red blood cells. A surgical drain was left in the peritoneum. Postoperatively, he developed hypotension, requiring vasopressors and prolonged continuation of stress dosing of hydrocortisone. Over the next 4 days, the patient was weaned off vasopressors, and his creatinine level was noted to increase from a baseline of 1.8 mg/dL to 4.4 mg/dL.

Dr. Rifkin, how do you think about renal recovery in the patient postnephrectomy, and should we be concerned with the dramatic rise in his creatinine level?

►Dr. Rifkin: Removal of renal mass will result in an initial reduction of GFR proportional to the amount of functional renal tissue removed. However, in as early as 1 week, the residual nephrons begin to compensate through various mechanisms, such as modulation of efferent and afferent arterioles and renal tissue growth by hypertrophy and hyperplasia.⁷ In the acute setting, it may be difficult to distinguish an acute renal injury vs physiological GFR reduction postnephron loss, but often the initially elevated creatinine level may normalize/stabilize over time. Other markers of kidney function should concomitantly be monitored, including urine output, electrolyte/acid-base status, and urine sediment examination. In this patient, although his creatinine level may be elevated over the first few days, if his urine output remains robust and the urine sediment examination is normal, my concern for permanent kidney injury would be lessened.

►Dr. Rifkin: The most common cause of acute kidney injury in hospitalized patients is acute tubular necrosis (ATN).⁸ However, in this patient, who was recovering well postoperatively, was hemodynamically stable with a robust urine output, and in whom no apparent cause for ATN could be identified, other diagnoses were more likely. Considering the abrupt onset of oligo-anuria, the most likely diagnosis was urinary tract obstruction, particularly given the frank blood and blood clots that were present in the urine. Additional possibilities might be a late surgical complication or infection. Surgical complications could range from direct damage to the renal parenchyma to urinary leakage into the peritoneum from the site of anastomosis or tissue injury. Infections introduced either intraoperatively or developed postoperatively could also cause this sudden drop in urine output, though one would expect more systemic symptoms with this. Given that this patient has a surgical drain in place in the peritoneum, I would recommend testing the creatinine level in the peritoneal fluid drainage. If it is comparable to serum levels, this would argue against a urine leak, as we would expect the level to be significantly elevated in a leak. In addition, he should have imaging of the urinary tract followed by procedures to decompress the presumed obstructed urinary tract. These procedures might include either cystoscopy with ureteral stent placement or percutaneous nephrostomy, depending on the result of the imaging.

►Dr. Bhatnagar: The creatinine level obtained from the surgical drain was roughly equivalent to the serum creatinine, decreasing suspicion for a urine leak as the cause of his findings. Cystoscopy with ureteral stent placement was performed with subsequent increase in both urine output and concomitant decrease in serum creatinine.

Around this time, the patient also began to note blurry vision. Evaluation revealed difficulty with visual field confrontation in the right lower quadrant, right eye ptosis, right eye impaired adduction, absent abduction and impaired upgaze, but intact downgaze. Diplopia was present with gaze in all directions. His constellation of physical examination findings were concerning for a pathologic lesion partially involving cranial nerves II and III, with definitive involvement of cranial nerve VI, but sparing of cranial nerve IV. Repeat MRI of the brain showed hemorrhage into the sellar mass, with ongoing mass effect on the optic chiasm and extension into the sinuses (eAppendix). These findings were consistent with pituitary apoplexy. Dr. Ananthakrishnan, can you tell us more about pituitary apoplexy?

►Dr. Ananthakrishnan: Pituitary apoplexy is a clinical syndrome resulting from acute hemorrhage or infarction of the pituitary gland. It typically occurs in patients with preexisting pituitary adenomas and is characterized by the onset of headache, fever, vomiting, meningismus, decreased consciousness, and sometimes death. In addition, given the location of the pituitary gland within the sella, rapid changes in size can result in compression of cranial nerves III, IV, and VI, as well as the optic chiasm, resulting in ophthalmoplegia and visual disturbances as seen in this patient.⁹

There are a multitude of causes of pituitary apoplexy, including alterations in coagulopathy, pituitary stimulation (eg, dynamic pituitary hormone testing), and both acute increases and decreases in blood flow.¹⁰ This patient likely had an ischemic event due to changes in vascular perfusion, spurred by both his blood loss intraoperatively and ongoing hematuria. Management of pituitary apoplexy is dependent on the patient’s hemodynamics, mass effect symptoms, electrolyte balances, and hormone dysfunction. The decision for conservative management vs surgical intervention should be made in consultation with both neurosurgery and endocrinology. Once the patient is hemodynamically stable, the next step in evaluating this patient should be repeating his hormone studies.

►Dr. Bhatnagar: An assessment of pituitary function was consistent with values obtained preoperatively. After multidisciplinary discussions, surgery was deferred, and hydrocortisone was reinitiated to reduce inflammation caused by bleeding into the mass. As the ophthalmoplegia improved, this was transitioned to dexamethasone.

Twelve days after admission, he was discharged to a subacute rehabilitation center, with improvement in his ophthalmoplegia and stabilization of his creatinine level and urine output.

►Anish Bhatnagar, MD, Chief Medical Resident, Veterans Affairs Boston Healthcare System (VABHS) and Beth Israel Deaconess Medical Center (BIDMC): The patient noted erectile dysfunction starting 4 years ago, with accompanied decreased libido. However, until recently, he was able to achieve acceptable erectile capacity with medications. As part of his previous evaluations for erectile dysfunction, the patient had 2 total testosterone levels checked 6 months apart, both low at 150 ng/dL and 38.3 ng/dL (reference range, 220-892). The results of additional hormone studies are shown in the Table. Dr. Ananthakrishnan, can you help us interpret these laboratory results and tell us what tests you might order next?

►Sonia Ananthakrishnan, MD, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center (BMC) and Assistant Professor of Medicine, Boston University School of Medicine (BUSM): When patients present with signs of hypogonadism and an initial low morning testosterone levels, the next test should be a confirmatory repeat morning testosterone level as was done in this case. If this level is also low (for most assays < 300 ng/dL), further evaluation for primary vs secondary hypogonadism should be pursued with measurement of luteinizing hormone and follicle-stimulating hormone levels. Secondary hypogonadism should be suspected when these levels are low or inappropriately normal in the setting of a low testosterone level as in this patient. This patient does not appear to be on any medication or have reversible illnesses that we traditionally think of as possibly causing these hormone irregularities. Key examples include medications such as gonadotropin-releasing hormone analogs, glucocorticoids, and opioids, as well as conditions such as hyperprolactinemia, sleep apnea, diabetes mellitus, anorexia nervosa, or other chronic systemic illnesses, including cirrhosis or lung disease. In this setting, further evaluation of the patient’s anterior pituitary function should be undertaken. Initial screening tests showed mildly elevated prolactin and low normal thyroid-stimulating hormone levels, with a relatively normal free thyroxine. Given these abnormalities in the context of the patient’s total testosterone level < 150 ng/dL, magnetic resonance imaging (MRI) of the anterior pituitary is indicated, and what I would recommend next for evaluation of pituitary and/or hypothalamic tumor or infiltrative disease.¹

►Dr. Bhatnagar: An MRI of the brain showed a large 2.7-cm sellar mass, with suprasellar extension and mass effect on the optic chiasm and pituitary infundibulum, partial extension into the right sphenoid sinus, and invasion into the right cavernous sinus. These findings were consistent with a pituitary macroadenoma. The patient was subsequently evaluated by a neurosurgeon who felt that because of the extension and compression of the mass, the patient would benefit from surgical resection.

Given his lower urinary tract symptoms, a prostate-specific antigen level was checked and returned elevated at 11.5 ng/mL. In the setting of these abnormalities, the patient underwent MRI of the abdomen, which noted a new 5.6-cm enhancing mass in the upper pole of his solitary right kidney, highly concerning for new RCC. After a multidisciplinary discussion, urology scheduled the patient for partial right nephrectomy first, with plans for pituitary resection only if the patient had adequate recovery following the urologic procedure.

Dr. Rifkin, this patient went straight from imaging to presumed diagnosis to planned surgical intervention without a confirmatory biopsy. In a patient who already has chronic kidney disease stage 4, why would we not want to pursue biopsy prior to this invasive procedure on his solitary kidney? In addition, given his baseline advanced renal disease, why pursue partial nephrectomy to delay initiation of hemodialysis instead of total nephrectomy and beginning hemodialysis?

►Ian Rifkin, MBBCh, PhD, MSc, Chief, Renal Section, VABHS, Section of Nephrology, BMC, and Associate Professor of Medicine, BUSM: In most cases, imaging alone is used to make a presumptive diagnosis of benign vs malignant renal masses. In one study, RCC was identified by MRI with 85% sensitivity and 76% specificity.² However, as imaging and biopsy techniques have advanced, there are progressing discussions regarding the utility of biopsy. That being said, there are a number of situations in which patients currently undergo biopsy, particularly when there is diagnostic uncertainty.³ In this patient, with a history of RCC and imaging findings concerning for RCC, biopsy is unnecessary given the high clinical suspicion.

Regarding the choice of partial vs total nephrectomy, there are 2 important distinctions to be made. The first is that though it was previously felt that early initiation of dialysis improves survival, newer studies suggest that early initiation based off of glomerular filtration rate (GFR) offers no survival benefits compared to delayed initiation.⁴ Second, though there is less clinical data to support this, there is a signal toward the use of partial nephrectomy decreasing mortality compared to radical nephrectomy in management of RCC.⁵ In this patient, partial nephrectomy may not only increase rates of survival, but also delay initiation of dialysis.

►Dr. Bhatnagar: Prior to undergoing partial right nephrectomy, a morning cortisol level was found to be 5.8 μg/dL with an associated corticotropin (ACTH) level of 26 pg/mL. Dr. Ananthakrishnan, how would you interpret these laboratory results and what might you recommend prior to surgery?

►Dr. Bhatnagar: The patient was started on hydrocortisone and underwent a successful laparoscopic partial right nephrectomy. During the procedure, an estimated 2.5 L of blood was lost, with transfusion of 3 units of packed red blood cells. A surgical drain was left in the peritoneum. Postoperatively, he developed hypotension, requiring vasopressors and prolonged continuation of stress dosing of hydrocortisone. Over the next 4 days, the patient was weaned off vasopressors, and his creatinine level was noted to increase from a baseline of 1.8 mg/dL to 4.4 mg/dL.

Dr. Rifkin, how do you think about renal recovery in the patient postnephrectomy, and should we be concerned with the dramatic rise in his creatinine level?

►Dr. Rifkin: Removal of renal mass will result in an initial reduction of GFR proportional to the amount of functional renal tissue removed. However, in as early as 1 week, the residual nephrons begin to compensate through various mechanisms, such as modulation of efferent and afferent arterioles and renal tissue growth by hypertrophy and hyperplasia.⁷ In the acute setting, it may be difficult to distinguish an acute renal injury vs physiological GFR reduction postnephron loss, but often the initially elevated creatinine level may normalize/stabilize over time. Other markers of kidney function should concomitantly be monitored, including urine output, electrolyte/acid-base status, and urine sediment examination. In this patient, although his creatinine level may be elevated over the first few days, if his urine output remains robust and the urine sediment examination is normal, my concern for permanent kidney injury would be lessened.

►Dr. Rifkin: The most common cause of acute kidney injury in hospitalized patients is acute tubular necrosis (ATN).⁸ However, in this patient, who was recovering well postoperatively, was hemodynamically stable with a robust urine output, and in whom no apparent cause for ATN could be identified, other diagnoses were more likely. Considering the abrupt onset of oligo-anuria, the most likely diagnosis was urinary tract obstruction, particularly given the frank blood and blood clots that were present in the urine. Additional possibilities might be a late surgical complication or infection. Surgical complications could range from direct damage to the renal parenchyma to urinary leakage into the peritoneum from the site of anastomosis or tissue injury. Infections introduced either intraoperatively or developed postoperatively could also cause this sudden drop in urine output, though one would expect more systemic symptoms with this. Given that this patient has a surgical drain in place in the peritoneum, I would recommend testing the creatinine level in the peritoneal fluid drainage. If it is comparable to serum levels, this would argue against a urine leak, as we would expect the level to be significantly elevated in a leak. In addition, he should have imaging of the urinary tract followed by procedures to decompress the presumed obstructed urinary tract. These procedures might include either cystoscopy with ureteral stent placement or percutaneous nephrostomy, depending on the result of the imaging.

►Dr. Bhatnagar: The creatinine level obtained from the surgical drain was roughly equivalent to the serum creatinine, decreasing suspicion for a urine leak as the cause of his findings. Cystoscopy with ureteral stent placement was performed with subsequent increase in both urine output and concomitant decrease in serum creatinine.

Around this time, the patient also began to note blurry vision. Evaluation revealed difficulty with visual field confrontation in the right lower quadrant, right eye ptosis, right eye impaired adduction, absent abduction and impaired upgaze, but intact downgaze. Diplopia was present with gaze in all directions. His constellation of physical examination findings were concerning for a pathologic lesion partially involving cranial nerves II and III, with definitive involvement of cranial nerve VI, but sparing of cranial nerve IV. Repeat MRI of the brain showed hemorrhage into the sellar mass, with ongoing mass effect on the optic chiasm and extension into the sinuses (eAppendix). These findings were consistent with pituitary apoplexy. Dr. Ananthakrishnan, can you tell us more about pituitary apoplexy?

►Dr. Ananthakrishnan: Pituitary apoplexy is a clinical syndrome resulting from acute hemorrhage or infarction of the pituitary gland. It typically occurs in patients with preexisting pituitary adenomas and is characterized by the onset of headache, fever, vomiting, meningismus, decreased consciousness, and sometimes death. In addition, given the location of the pituitary gland within the sella, rapid changes in size can result in compression of cranial nerves III, IV, and VI, as well as the optic chiasm, resulting in ophthalmoplegia and visual disturbances as seen in this patient.⁹

There are a multitude of causes of pituitary apoplexy, including alterations in coagulopathy, pituitary stimulation (eg, dynamic pituitary hormone testing), and both acute increases and decreases in blood flow.¹⁰ This patient likely had an ischemic event due to changes in vascular perfusion, spurred by both his blood loss intraoperatively and ongoing hematuria. Management of pituitary apoplexy is dependent on the patient’s hemodynamics, mass effect symptoms, electrolyte balances, and hormone dysfunction. The decision for conservative management vs surgical intervention should be made in consultation with both neurosurgery and endocrinology. Once the patient is hemodynamically stable, the next step in evaluating this patient should be repeating his hormone studies.

►Dr. Bhatnagar: An assessment of pituitary function was consistent with values obtained preoperatively. After multidisciplinary discussions, surgery was deferred, and hydrocortisone was reinitiated to reduce inflammation caused by bleeding into the mass. As the ophthalmoplegia improved, this was transitioned to dexamethasone.

Twelve days after admission, he was discharged to a subacute rehabilitation center, with improvement in his ophthalmoplegia and stabilization of his creatinine level and urine output.

►Anish Bhatnagar, MD, Chief Medical Resident, Veterans Affairs Boston Healthcare System (VABHS) and Beth Israel Deaconess Medical Center (BIDMC): The patient noted erectile dysfunction starting 4 years ago, with accompanied decreased libido. However, until recently, he was able to achieve acceptable erectile capacity with medications. As part of his previous evaluations for erectile dysfunction, the patient had 2 total testosterone levels checked 6 months apart, both low at 150 ng/dL and 38.3 ng/dL (reference range, 220-892). The results of additional hormone studies are shown in the Table. Dr. Ananthakrishnan, can you help us interpret these laboratory results and tell us what tests you might order next?

►Sonia Ananthakrishnan, MD, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center (BMC) and Assistant Professor of Medicine, Boston University School of Medicine (BUSM): When patients present with signs of hypogonadism and an initial low morning testosterone levels, the next test should be a confirmatory repeat morning testosterone level as was done in this case. If this level is also low (for most assays < 300 ng/dL), further evaluation for primary vs secondary hypogonadism should be pursued with measurement of luteinizing hormone and follicle-stimulating hormone levels. Secondary hypogonadism should be suspected when these levels are low or inappropriately normal in the setting of a low testosterone level as in this patient. This patient does not appear to be on any medication or have reversible illnesses that we traditionally think of as possibly causing these hormone irregularities. Key examples include medications such as gonadotropin-releasing hormone analogs, glucocorticoids, and opioids, as well as conditions such as hyperprolactinemia, sleep apnea, diabetes mellitus, anorexia nervosa, or other chronic systemic illnesses, including cirrhosis or lung disease. In this setting, further evaluation of the patient’s anterior pituitary function should be undertaken. Initial screening tests showed mildly elevated prolactin and low normal thyroid-stimulating hormone levels, with a relatively normal free thyroxine. Given these abnormalities in the context of the patient’s total testosterone level < 150 ng/dL, magnetic resonance imaging (MRI) of the anterior pituitary is indicated, and what I would recommend next for evaluation of pituitary and/or hypothalamic tumor or infiltrative disease.¹

►Dr. Bhatnagar: An MRI of the brain showed a large 2.7-cm sellar mass, with suprasellar extension and mass effect on the optic chiasm and pituitary infundibulum, partial extension into the right sphenoid sinus, and invasion into the right cavernous sinus. These findings were consistent with a pituitary macroadenoma. The patient was subsequently evaluated by a neurosurgeon who felt that because of the extension and compression of the mass, the patient would benefit from surgical resection.

Given his lower urinary tract symptoms, a prostate-specific antigen level was checked and returned elevated at 11.5 ng/mL. In the setting of these abnormalities, the patient underwent MRI of the abdomen, which noted a new 5.6-cm enhancing mass in the upper pole of his solitary right kidney, highly concerning for new RCC. After a multidisciplinary discussion, urology scheduled the patient for partial right nephrectomy first, with plans for pituitary resection only if the patient had adequate recovery following the urologic procedure.

Dr. Rifkin, this patient went straight from imaging to presumed diagnosis to planned surgical intervention without a confirmatory biopsy. In a patient who already has chronic kidney disease stage 4, why would we not want to pursue biopsy prior to this invasive procedure on his solitary kidney? In addition, given his baseline advanced renal disease, why pursue partial nephrectomy to delay initiation of hemodialysis instead of total nephrectomy and beginning hemodialysis?

►Ian Rifkin, MBBCh, PhD, MSc, Chief, Renal Section, VABHS, Section of Nephrology, BMC, and Associate Professor of Medicine, BUSM: In most cases, imaging alone is used to make a presumptive diagnosis of benign vs malignant renal masses. In one study, RCC was identified by MRI with 85% sensitivity and 76% specificity.² However, as imaging and biopsy techniques have advanced, there are progressing discussions regarding the utility of biopsy. That being said, there are a number of situations in which patients currently undergo biopsy, particularly when there is diagnostic uncertainty.³ In this patient, with a history of RCC and imaging findings concerning for RCC, biopsy is unnecessary given the high clinical suspicion.

Regarding the choice of partial vs total nephrectomy, there are 2 important distinctions to be made. The first is that though it was previously felt that early initiation of dialysis improves survival, newer studies suggest that early initiation based off of glomerular filtration rate (GFR) offers no survival benefits compared to delayed initiation.⁴ Second, though there is less clinical data to support this, there is a signal toward the use of partial nephrectomy decreasing mortality compared to radical nephrectomy in management of RCC.⁵ In this patient, partial nephrectomy may not only increase rates of survival, but also delay initiation of dialysis.

►Dr. Bhatnagar: Prior to undergoing partial right nephrectomy, a morning cortisol level was found to be 5.8 μg/dL with an associated corticotropin (ACTH) level of 26 pg/mL. Dr. Ananthakrishnan, how would you interpret these laboratory results and what might you recommend prior to surgery?

►Dr. Bhatnagar: The patient was started on hydrocortisone and underwent a successful laparoscopic partial right nephrectomy. During the procedure, an estimated 2.5 L of blood was lost, with transfusion of 3 units of packed red blood cells. A surgical drain was left in the peritoneum. Postoperatively, he developed hypotension, requiring vasopressors and prolonged continuation of stress dosing of hydrocortisone. Over the next 4 days, the patient was weaned off vasopressors, and his creatinine level was noted to increase from a baseline of 1.8 mg/dL to 4.4 mg/dL.

Dr. Rifkin, how do you think about renal recovery in the patient postnephrectomy, and should we be concerned with the dramatic rise in his creatinine level?

►Dr. Rifkin: Removal of renal mass will result in an initial reduction of GFR proportional to the amount of functional renal tissue removed. However, in as early as 1 week, the residual nephrons begin to compensate through various mechanisms, such as modulation of efferent and afferent arterioles and renal tissue growth by hypertrophy and hyperplasia.⁷ In the acute setting, it may be difficult to distinguish an acute renal injury vs physiological GFR reduction postnephron loss, but often the initially elevated creatinine level may normalize/stabilize over time. Other markers of kidney function should concomitantly be monitored, including urine output, electrolyte/acid-base status, and urine sediment examination. In this patient, although his creatinine level may be elevated over the first few days, if his urine output remains robust and the urine sediment examination is normal, my concern for permanent kidney injury would be lessened.

►Dr. Rifkin: The most common cause of acute kidney injury in hospitalized patients is acute tubular necrosis (ATN).⁸ However, in this patient, who was recovering well postoperatively, was hemodynamically stable with a robust urine output, and in whom no apparent cause for ATN could be identified, other diagnoses were more likely. Considering the abrupt onset of oligo-anuria, the most likely diagnosis was urinary tract obstruction, particularly given the frank blood and blood clots that were present in the urine. Additional possibilities might be a late surgical complication or infection. Surgical complications could range from direct damage to the renal parenchyma to urinary leakage into the peritoneum from the site of anastomosis or tissue injury. Infections introduced either intraoperatively or developed postoperatively could also cause this sudden drop in urine output, though one would expect more systemic symptoms with this. Given that this patient has a surgical drain in place in the peritoneum, I would recommend testing the creatinine level in the peritoneal fluid drainage. If it is comparable to serum levels, this would argue against a urine leak, as we would expect the level to be significantly elevated in a leak. In addition, he should have imaging of the urinary tract followed by procedures to decompress the presumed obstructed urinary tract. These procedures might include either cystoscopy with ureteral stent placement or percutaneous nephrostomy, depending on the result of the imaging.

►Dr. Bhatnagar: The creatinine level obtained from the surgical drain was roughly equivalent to the serum creatinine, decreasing suspicion for a urine leak as the cause of his findings. Cystoscopy with ureteral stent placement was performed with subsequent increase in both urine output and concomitant decrease in serum creatinine.

Around this time, the patient also began to note blurry vision. Evaluation revealed difficulty with visual field confrontation in the right lower quadrant, right eye ptosis, right eye impaired adduction, absent abduction and impaired upgaze, but intact downgaze. Diplopia was present with gaze in all directions. His constellation of physical examination findings were concerning for a pathologic lesion partially involving cranial nerves II and III, with definitive involvement of cranial nerve VI, but sparing of cranial nerve IV. Repeat MRI of the brain showed hemorrhage into the sellar mass, with ongoing mass effect on the optic chiasm and extension into the sinuses (eAppendix). These findings were consistent with pituitary apoplexy. Dr. Ananthakrishnan, can you tell us more about pituitary apoplexy?

►Dr. Ananthakrishnan: Pituitary apoplexy is a clinical syndrome resulting from acute hemorrhage or infarction of the pituitary gland. It typically occurs in patients with preexisting pituitary adenomas and is characterized by the onset of headache, fever, vomiting, meningismus, decreased consciousness, and sometimes death. In addition, given the location of the pituitary gland within the sella, rapid changes in size can result in compression of cranial nerves III, IV, and VI, as well as the optic chiasm, resulting in ophthalmoplegia and visual disturbances as seen in this patient.⁹

There are a multitude of causes of pituitary apoplexy, including alterations in coagulopathy, pituitary stimulation (eg, dynamic pituitary hormone testing), and both acute increases and decreases in blood flow.¹⁰ This patient likely had an ischemic event due to changes in vascular perfusion, spurred by both his blood loss intraoperatively and ongoing hematuria. Management of pituitary apoplexy is dependent on the patient’s hemodynamics, mass effect symptoms, electrolyte balances, and hormone dysfunction. The decision for conservative management vs surgical intervention should be made in consultation with both neurosurgery and endocrinology. Once the patient is hemodynamically stable, the next step in evaluating this patient should be repeating his hormone studies.

►Dr. Bhatnagar: An assessment of pituitary function was consistent with values obtained preoperatively. After multidisciplinary discussions, surgery was deferred, and hydrocortisone was reinitiated to reduce inflammation caused by bleeding into the mass. As the ophthalmoplegia improved, this was transitioned to dexamethasone.

Twelve days after admission, he was discharged to a subacute rehabilitation center, with improvement in his ophthalmoplegia and stabilization of his creatinine level and urine output.

You’re rounding in the nursery and informed of the following about one of your new patients: He’s a 38-week-old infant delivered to a mother diagnosed with syphilis at 12 weeks’ gestation at her initial prenatal visit. Her rapid plasma reagin (RPR) was 1:64 and the fluorescent treponemal antibody–absorption (FTA-ABS) test was positive. By report she was appropriately treated. Maternal RPRs obtained at 18 and 28 weeks’ gestation were 1:16 and 1:4, respectively. Maternal RPR at delivery and the infant’s RPR obtained shortly after birth were both 1:4. The mother wants to know if her baby is infected.

One result of syphilis during pregnancy is intrauterine infection and resultant congenital disease in the infant. Before you answer this mother, let’s discuss syphilis.

Congenital syphilis is a significant public health problem. In 2021, there were a total of 2,677 cases reported for a rate of 74.1 per 100,000 live births. Between 2020 and 2021, the number of cases of congenital syphilis increased 24.1% (2,158-2,677 cases), concurrent with a 45.8% increase (10.7-15.6 per 100,000) in the rate of primary and secondary syphilis in women aged 15-44 years. Between 2012 and 2021, the number of cases of congenital syphilis increased 701.5% (334-2,677 cases) and the increase in rates of primary and secondary syphilis in women aged 15-44 was 642.9% over the same period.

Why are the rates of congenital syphilis increasing? Most cases result from a lack of prenatal care and thus no testing for syphilis. The next most common cause is inadequate maternal treatment.

Congenital syphilis usually is acquired through transplacental transmission of spirochetes in the maternal bloodstream. Occasionally, it occurs at delivery via direct contact with maternal lesions. It is not transmitted in breast milk. Transmission of syphilis:

• Can occur any time during pregnancy.
• Is more likely to occur in women with untreated primary or secondary disease (60%-100%).
• Is approximately 40% in those with early latent syphilis and less than 8% in mothers with late latent syphilis.
• Is higher in women coinfected with HIV since they more frequently receive no prenatal care and their disease is inadequately treated.

Coinfection with syphilis may also increase the rate of mother-to-child transmission of HIV.

Untreated early syphilis during pregnancy results in spontaneous abortion, stillbirth, or perinatal death in up to 40% of cases. Infected newborns with early congenital syphilis can be asymptomatic or have evidence of hepatosplenomegaly, generalized lymphadenopathy, nasal discharge that is occasionally bloody, rash, and skeletal abnormalities (osteochondritis and periostitis). Other manifestations include edema, hemolytic anemia, jaundice, pneumonia, pseudoparalysis, and thrombocytopenia. Asymptomatic infants may have abnormal cerebrospinal fluid findings including elevated CSF white cell count, elevated protein, and a reactive venereal disease research laboratory test.

Late congenital syphilis, defined as the onset of symptoms after 2 years of age is secondary to scarring or persistent inflammation and gumma formation in a variety of tissues. It occurs in up to 40% of cases of untreated maternal disease. Most cases can be prevented by maternal treatment and treatment of the infant within the first 3 months of life. Common clinical manifestations include interstitial keratitis, sensorineural hearing loss, frontal bossing, saddle nose, Hutchinson teeth, mulberry molars, perforation of the hard palate, anterior bowing of the tibia (saber shins), and other skeletal abnormalities.

Diagnostic tests. Maternal diagnosis is dependent upon knowing the results of both a nontreponemal (RPR, VDRL) and a confirmatory treponemal test (TP-PA, TP-EIA, TP-CIA, FTA-ABS,) before or at delivery. TP-PA is the preferred test. When maternal disease is confirmed, the newborn should have the same quantitative nontreponemal test as the mother. A confirmatory treponemal test is not required

Evaluation and treatment. It’s imperative that children born to mothers with a reactive test, regardless of their treatment status, have a thorough exam performed before hospital discharge. The provider must determine what additional interventions should be performed.

The American Academy of Pediatrics and the Centers for Disease Control and Prevention (www.cdc.gov/std/treatment-guidelines/congenital-syphilis.htm) have developed standard algorithms for the diagnostic approach and treatment of infants born to mothers with reactive serologic tests for syphilis. It is available in the Red Book for AAP members (https://publications.aap.org/redbook). Recommendations based on various scenarios for neonates up to 1 month of age include proven or highly probable congenital syphilis, possible congenital syphilis, congenital syphilis less likely, and congenital syphilis unlikely. It is beyond the scope of this article to list the criteria and evaluation for each scenario. The reader is referred to the algorithm.

If syphilis is suspected in infants or children older than 1 month, the challenge is to determine if it is untreated congenital syphilis or acquired syphilis. Maternal syphilis status should be determined. Evaluation for congenital syphilis in this age group includes CSF analysis for VDRL, cell count and protein, CBC with differential and platelets, hepatic panel, abdominal ultrasound, long-bone radiographs, chest radiograph, neuroimaging, auditory brain stem response, and HIV testing.

Let’s go back to your patient. The mother was diagnosed with syphilis during pregnancy. You confirm that she was treated with benzathine penicillin G, and the course was completed at least 4 weeks before delivery. Treatment with any other drug during pregnancy is not appropriate. The RPR has declined, and the infant’s titer is equal to or less than four times the maternal titer. The exam is significant for generalized adenopathy and slightly bloody nasal discharge. This infant has two findings consistent with congenital syphilis regardless of RPR titer or treatment status. This places him in the proven or highly probable congenital syphilis group. Management includes CSF analysis (VDRL, cell count, and protein), CBC with differential and platelet count, and treatment with penicillin G for 10 days. Additional tests as clinically indicated include: long-bone radiograph, chest radiography, aspartate aminotranferase and alanine aminotransferase levels, neuroimaging, ophthalmologic exam, and auditory brain stem response. Despite maternal treatment, this newborn has congenital syphilis. The same nontreponemal test should be obtained every 2-3 months until it is nonreactive. It should be nonreactive by 6 months. If the infection persists to 6-12 months post treatment, reevaluation including CSF analysis and retreatment may be indicated.

Congenital syphilis can be prevented by maternal screening, diagnosis, and treatment. When that fails it is up to us to diagnosis and adequately treat our patients.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

You’re rounding in the nursery and informed of the following about one of your new patients: He’s a 38-week-old infant delivered to a mother diagnosed with syphilis at 12 weeks’ gestation at her initial prenatal visit. Her rapid plasma reagin (RPR) was 1:64 and the fluorescent treponemal antibody–absorption (FTA-ABS) test was positive. By report she was appropriately treated. Maternal RPRs obtained at 18 and 28 weeks’ gestation were 1:16 and 1:4, respectively. Maternal RPR at delivery and the infant’s RPR obtained shortly after birth were both 1:4. The mother wants to know if her baby is infected.

One result of syphilis during pregnancy is intrauterine infection and resultant congenital disease in the infant. Before you answer this mother, let’s discuss syphilis.

Congenital syphilis is a significant public health problem. In 2021, there were a total of 2,677 cases reported for a rate of 74.1 per 100,000 live births. Between 2020 and 2021, the number of cases of congenital syphilis increased 24.1% (2,158-2,677 cases), concurrent with a 45.8% increase (10.7-15.6 per 100,000) in the rate of primary and secondary syphilis in women aged 15-44 years. Between 2012 and 2021, the number of cases of congenital syphilis increased 701.5% (334-2,677 cases) and the increase in rates of primary and secondary syphilis in women aged 15-44 was 642.9% over the same period.

Why are the rates of congenital syphilis increasing? Most cases result from a lack of prenatal care and thus no testing for syphilis. The next most common cause is inadequate maternal treatment.

Congenital syphilis usually is acquired through transplacental transmission of spirochetes in the maternal bloodstream. Occasionally, it occurs at delivery via direct contact with maternal lesions. It is not transmitted in breast milk. Transmission of syphilis:

• Can occur any time during pregnancy.
• Is more likely to occur in women with untreated primary or secondary disease (60%-100%).
• Is approximately 40% in those with early latent syphilis and less than 8% in mothers with late latent syphilis.
• Is higher in women coinfected with HIV since they more frequently receive no prenatal care and their disease is inadequately treated.

Coinfection with syphilis may also increase the rate of mother-to-child transmission of HIV.

Untreated early syphilis during pregnancy results in spontaneous abortion, stillbirth, or perinatal death in up to 40% of cases. Infected newborns with early congenital syphilis can be asymptomatic or have evidence of hepatosplenomegaly, generalized lymphadenopathy, nasal discharge that is occasionally bloody, rash, and skeletal abnormalities (osteochondritis and periostitis). Other manifestations include edema, hemolytic anemia, jaundice, pneumonia, pseudoparalysis, and thrombocytopenia. Asymptomatic infants may have abnormal cerebrospinal fluid findings including elevated CSF white cell count, elevated protein, and a reactive venereal disease research laboratory test.

Late congenital syphilis, defined as the onset of symptoms after 2 years of age is secondary to scarring or persistent inflammation and gumma formation in a variety of tissues. It occurs in up to 40% of cases of untreated maternal disease. Most cases can be prevented by maternal treatment and treatment of the infant within the first 3 months of life. Common clinical manifestations include interstitial keratitis, sensorineural hearing loss, frontal bossing, saddle nose, Hutchinson teeth, mulberry molars, perforation of the hard palate, anterior bowing of the tibia (saber shins), and other skeletal abnormalities.

Diagnostic tests. Maternal diagnosis is dependent upon knowing the results of both a nontreponemal (RPR, VDRL) and a confirmatory treponemal test (TP-PA, TP-EIA, TP-CIA, FTA-ABS,) before or at delivery. TP-PA is the preferred test. When maternal disease is confirmed, the newborn should have the same quantitative nontreponemal test as the mother. A confirmatory treponemal test is not required

Evaluation and treatment. It’s imperative that children born to mothers with a reactive test, regardless of their treatment status, have a thorough exam performed before hospital discharge. The provider must determine what additional interventions should be performed.

The American Academy of Pediatrics and the Centers for Disease Control and Prevention (www.cdc.gov/std/treatment-guidelines/congenital-syphilis.htm) have developed standard algorithms for the diagnostic approach and treatment of infants born to mothers with reactive serologic tests for syphilis. It is available in the Red Book for AAP members (https://publications.aap.org/redbook). Recommendations based on various scenarios for neonates up to 1 month of age include proven or highly probable congenital syphilis, possible congenital syphilis, congenital syphilis less likely, and congenital syphilis unlikely. It is beyond the scope of this article to list the criteria and evaluation for each scenario. The reader is referred to the algorithm.

If syphilis is suspected in infants or children older than 1 month, the challenge is to determine if it is untreated congenital syphilis or acquired syphilis. Maternal syphilis status should be determined. Evaluation for congenital syphilis in this age group includes CSF analysis for VDRL, cell count and protein, CBC with differential and platelets, hepatic panel, abdominal ultrasound, long-bone radiographs, chest radiograph, neuroimaging, auditory brain stem response, and HIV testing.

Let’s go back to your patient. The mother was diagnosed with syphilis during pregnancy. You confirm that she was treated with benzathine penicillin G, and the course was completed at least 4 weeks before delivery. Treatment with any other drug during pregnancy is not appropriate. The RPR has declined, and the infant’s titer is equal to or less than four times the maternal titer. The exam is significant for generalized adenopathy and slightly bloody nasal discharge. This infant has two findings consistent with congenital syphilis regardless of RPR titer or treatment status. This places him in the proven or highly probable congenital syphilis group. Management includes CSF analysis (VDRL, cell count, and protein), CBC with differential and platelet count, and treatment with penicillin G for 10 days. Additional tests as clinically indicated include: long-bone radiograph, chest radiography, aspartate aminotranferase and alanine aminotransferase levels, neuroimaging, ophthalmologic exam, and auditory brain stem response. Despite maternal treatment, this newborn has congenital syphilis. The same nontreponemal test should be obtained every 2-3 months until it is nonreactive. It should be nonreactive by 6 months. If the infection persists to 6-12 months post treatment, reevaluation including CSF analysis and retreatment may be indicated.

Congenital syphilis can be prevented by maternal screening, diagnosis, and treatment. When that fails it is up to us to diagnosis and adequately treat our patients.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

You’re rounding in the nursery and informed of the following about one of your new patients: He’s a 38-week-old infant delivered to a mother diagnosed with syphilis at 12 weeks’ gestation at her initial prenatal visit. Her rapid plasma reagin (RPR) was 1:64 and the fluorescent treponemal antibody–absorption (FTA-ABS) test was positive. By report she was appropriately treated. Maternal RPRs obtained at 18 and 28 weeks’ gestation were 1:16 and 1:4, respectively. Maternal RPR at delivery and the infant’s RPR obtained shortly after birth were both 1:4. The mother wants to know if her baby is infected.

One result of syphilis during pregnancy is intrauterine infection and resultant congenital disease in the infant. Before you answer this mother, let’s discuss syphilis.

Congenital syphilis is a significant public health problem. In 2021, there were a total of 2,677 cases reported for a rate of 74.1 per 100,000 live births. Between 2020 and 2021, the number of cases of congenital syphilis increased 24.1% (2,158-2,677 cases), concurrent with a 45.8% increase (10.7-15.6 per 100,000) in the rate of primary and secondary syphilis in women aged 15-44 years. Between 2012 and 2021, the number of cases of congenital syphilis increased 701.5% (334-2,677 cases) and the increase in rates of primary and secondary syphilis in women aged 15-44 was 642.9% over the same period.

Why are the rates of congenital syphilis increasing? Most cases result from a lack of prenatal care and thus no testing for syphilis. The next most common cause is inadequate maternal treatment.

Congenital syphilis usually is acquired through transplacental transmission of spirochetes in the maternal bloodstream. Occasionally, it occurs at delivery via direct contact with maternal lesions. It is not transmitted in breast milk. Transmission of syphilis:

• Can occur any time during pregnancy.
• Is more likely to occur in women with untreated primary or secondary disease (60%-100%).
• Is approximately 40% in those with early latent syphilis and less than 8% in mothers with late latent syphilis.
• Is higher in women coinfected with HIV since they more frequently receive no prenatal care and their disease is inadequately treated.

Coinfection with syphilis may also increase the rate of mother-to-child transmission of HIV.

Untreated early syphilis during pregnancy results in spontaneous abortion, stillbirth, or perinatal death in up to 40% of cases. Infected newborns with early congenital syphilis can be asymptomatic or have evidence of hepatosplenomegaly, generalized lymphadenopathy, nasal discharge that is occasionally bloody, rash, and skeletal abnormalities (osteochondritis and periostitis). Other manifestations include edema, hemolytic anemia, jaundice, pneumonia, pseudoparalysis, and thrombocytopenia. Asymptomatic infants may have abnormal cerebrospinal fluid findings including elevated CSF white cell count, elevated protein, and a reactive venereal disease research laboratory test.

Late congenital syphilis, defined as the onset of symptoms after 2 years of age is secondary to scarring or persistent inflammation and gumma formation in a variety of tissues. It occurs in up to 40% of cases of untreated maternal disease. Most cases can be prevented by maternal treatment and treatment of the infant within the first 3 months of life. Common clinical manifestations include interstitial keratitis, sensorineural hearing loss, frontal bossing, saddle nose, Hutchinson teeth, mulberry molars, perforation of the hard palate, anterior bowing of the tibia (saber shins), and other skeletal abnormalities.

Diagnostic tests. Maternal diagnosis is dependent upon knowing the results of both a nontreponemal (RPR, VDRL) and a confirmatory treponemal test (TP-PA, TP-EIA, TP-CIA, FTA-ABS,) before or at delivery. TP-PA is the preferred test. When maternal disease is confirmed, the newborn should have the same quantitative nontreponemal test as the mother. A confirmatory treponemal test is not required

Evaluation and treatment. It’s imperative that children born to mothers with a reactive test, regardless of their treatment status, have a thorough exam performed before hospital discharge. The provider must determine what additional interventions should be performed.

The American Academy of Pediatrics and the Centers for Disease Control and Prevention (www.cdc.gov/std/treatment-guidelines/congenital-syphilis.htm) have developed standard algorithms for the diagnostic approach and treatment of infants born to mothers with reactive serologic tests for syphilis. It is available in the Red Book for AAP members (https://publications.aap.org/redbook). Recommendations based on various scenarios for neonates up to 1 month of age include proven or highly probable congenital syphilis, possible congenital syphilis, congenital syphilis less likely, and congenital syphilis unlikely. It is beyond the scope of this article to list the criteria and evaluation for each scenario. The reader is referred to the algorithm.

If syphilis is suspected in infants or children older than 1 month, the challenge is to determine if it is untreated congenital syphilis or acquired syphilis. Maternal syphilis status should be determined. Evaluation for congenital syphilis in this age group includes CSF analysis for VDRL, cell count and protein, CBC with differential and platelets, hepatic panel, abdominal ultrasound, long-bone radiographs, chest radiograph, neuroimaging, auditory brain stem response, and HIV testing.

Let’s go back to your patient. The mother was diagnosed with syphilis during pregnancy. You confirm that she was treated with benzathine penicillin G, and the course was completed at least 4 weeks before delivery. Treatment with any other drug during pregnancy is not appropriate. The RPR has declined, and the infant’s titer is equal to or less than four times the maternal titer. The exam is significant for generalized adenopathy and slightly bloody nasal discharge. This infant has two findings consistent with congenital syphilis regardless of RPR titer or treatment status. This places him in the proven or highly probable congenital syphilis group. Management includes CSF analysis (VDRL, cell count, and protein), CBC with differential and platelet count, and treatment with penicillin G for 10 days. Additional tests as clinically indicated include: long-bone radiograph, chest radiography, aspartate aminotranferase and alanine aminotransferase levels, neuroimaging, ophthalmologic exam, and auditory brain stem response. Despite maternal treatment, this newborn has congenital syphilis. The same nontreponemal test should be obtained every 2-3 months until it is nonreactive. It should be nonreactive by 6 months. If the infection persists to 6-12 months post treatment, reevaluation including CSF analysis and retreatment may be indicated.

Congenital syphilis can be prevented by maternal screening, diagnosis, and treatment. When that fails it is up to us to diagnosis and adequately treat our patients.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

Nearly two-thirds of people who had persistent COVID-19 symptoms during the first 2 years of the pandemic were women, according to a new study published in JAMA.

The global study also found that about 6% of people with symptomatic infections had long COVID in 2020 and 2021. The risk for long COVID seemed to be greater among those who needed hospitalization, especially those who needed intensive care.

“Quantifying the number of individuals with long COVID may help policy makers ensure adequate access to services to guide people toward recovery, return to the workplace or school, and restore their mental health and social life,” the researchers wrote.

The study team, which included dozens of researchers across nearly every continent, analyzed data from 54 studies and two databases for more than 1 million patients in 22 countries who had symptomatic COVID infections in 2020 and 2021. They looked at three long COVID symptom types: persistent fatigue with bodily pain or mood swings, ongoing respiratory problems, and cognitive issues. The study included people aged 4-66.

Overall, 6.2% of people reported one of the long COVID symptom types, including 3.7% with ongoing respiratory problems, 3.2% with persistent fatigue and bodily pain or mood swings, and 2.2% with cognitive problems. Among those with long COVID, 38% of people reported more than one symptom cluster.

At 3 months after infection, long COVID symptoms were nearly twice as common in women who were at least 20 years old at 10.6%, compared with men who were at least 20 years old at 5.4%.

Children and teens appeared to have lower risks of long COVID. About 2.8% of patients under age 20 with symptomatic infection developed long-term issues.

The estimated average duration of long COVID symptoms was 9 months among hospitalized patients and 4 months among those who weren’t hospitalized. About 15% of people with long COVID symptoms 3 months after the initial infection continued to have symptoms at 12 months.

The study was largely based on detailed data from ongoing COVID-19 studies in the United States, Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, and Switzerland, according to UPI. It was supplemented by published data and research conducted as part of the Global Burden of Diseases, Injuries and Risk Factors Study. The dozens of researchers are referred to as “Global Burden of Disease Long COVID Collaborators.”

The study had limitations, the researchers said, including the assumption that long COVID follows a similar course in all countries. Additional studies may show how long COVID symptoms and severity may vary in different countries and continents.

Ultimately, ongoing studies of large numbers of people with long COVID could help scientists and public health officials understand risk factors and ways to treat the debilitating condition, the study authors wrote, noting that “postinfection fatigue syndrome” has been reported before, namely during the 1918 flu pandemic, after the SARS outbreak in 2003, and after the Ebola epidemic in West Africa in 2014.

“Similar symptoms have been reported after other viral infections, including the Epstein-Barr virus, mononucleosis, and dengue, as well as after nonviral infections such as Q fever, Lyme disease and giardiasis,” they wrote.

Several study investigators reported receiving grants and personal fees from a variety of sources.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

• Wanted life to feel normal (50%).
• Freedom (45%).
• It’s no one’s business (40%).
• COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

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

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

• Wanted life to feel normal (50%).
• Freedom (45%).
• It’s no one’s business (40%).
• COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

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

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

• Wanted life to feel normal (50%).
• Freedom (45%).
• It’s no one’s business (40%).
• COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

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

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Weeks after Jeannie Volpe caught COVID-19 in November 2020, she could no longer do her job running sexual assault support groups in Anniston, Ala., because she kept forgetting the details that survivors had shared with her. “People were telling me they were having to revisit their traumatic memories, which isn’t fair to anybody,” the 47-year-old says.

Ms. Volpe has been diagnosed with long-COVID autonomic dysfunction, which includes severe muscle pain, depression, anxiety, and a loss of thinking skills. Some of her symptoms are more commonly known as brain fog, and they’re among the most frequent problems reported by people who have long-term issues after a bout of COVID-19.

Many experts and medical professionals say they haven’t even begun to scratch the surface of what impact this will have in years to come. 

“I’m very worried that we have an epidemic of neurologic dysfunction coming down the pike,” says Pamela Davis, MD, PhD, a research professor at Case Western Reserve University, Cleveland.

In the 2 years Ms. Volpe has been living with long COVID, her executive function – the mental processes that enable people to focus attention, retain information, and multitask – has been so diminished that she had to relearn to drive. One of the various doctors assessing her has suggested speech therapy to help Ms. Volpe relearn how to form words. “I can see the words I want to say in my mind, but I can’t make them come out of my mouth,” she says in a sluggish voice that gives away her condition. 

All of those symptoms make it difficult for her to care for herself. Without a job and health insurance, Ms. Volpe says she’s researched assisted suicide in the states that allow it but has ultimately decided she wants to live. 

“People tell you things like you should be grateful you survived it, and you should; but you shouldn’t expect somebody to not grieve after losing their autonomy, their career, their finances.”

The findings of researchers studying the brain effects of COVID-19 reinforce what people with long COVID have been dealing with from the start. Their experiences aren’t imaginary; they’re consistent with neurological disorders – including myalgic encephalomyelitis, also known as chronic fatigue syndrome, or ME/CFS – which carry much more weight in the public imagination than the term brain fog, which can often be used dismissively.

Studies have found that COVID-19 is linked to conditions such as strokes; seizures; and mood, memory, and movement disorders. 

While there are still a lot of unanswered questions about exactly how COVID-19 affects the brain and what the long-term effects are, there’s enough reason to suggest people should be trying to avoid both infection and reinfection until researchers get more answers.

Worldwide, it’s estimated that COVID-19 has contributed to more than 40 million new cases of neurological disorders, says Ziyad Al-Aly, MD, a clinical epidemiologist and long COVID researcher at Washington University in St. Louis. In his latest study of 14 million medical records of the U.S. Department of Veterans Affairs, the country’s largest integrated health care system, researchers found that regardless of age, gender, race, and lifestyle, people who have had COVID-19 are at a higher risk of getting a wide array of 44 neurological conditions after the first year of infection.

He noted that some of the conditions, such as headaches and mild decline in memory and sharpness, may improve and go away over time. But others that showed up, such as stroke, encephalitis (inflammation of the brain), and Guillain-Barré syndrome (a rare disorder in which the body’s immune system attacks the nerves), often lead to lasting damage. Dr. Al-Aly’s team found that neurological conditions were 7% more likely in those who had COVID-19 than in those who had never been infected. 

What’s more, researchers noticed that compared with control groups, the risk of post-COVID thinking problems was more pronounced in people in their 30s, 40s, and 50s – a group that usually would be very unlikely to have these problems. For those over the age of 60, the risks stood out less because at that stage of life, such thinking problems aren’t as rare.

Another study of the veterans system last year showed that COVID-19 survivors were at a 46% higher risk of considering suicide after 1 year.

“We need to be paying attention to this,” says Dr. Al-Aly.  “What we’ve seen is really the tip of the iceberg.” He worries that millions of people, including youths, will lose out on employment and education while dealing with long-term disabilities – and the economic and societal implications of such a fallout. “What we will all be left with is the aftermath of sheer devastation in some people’s lives,” he says.

Igor Koralnik, MD, chief of neuro-infectious disease and global neurology at Northwestern University, Chicago, has been running a specialized long COVID clinic. His team published a paper in March 2021 detailing what they saw in their first 100 patients. “About half the population in the study missed at least 10 days of work. This is going to have persistent impact on the workforce,” Dr. Koralnik said in a podcast posted on the Northwestern website. “We have seen that not only [do] patients have symptoms, but they have decreased quality of life.”

For older people and their caregivers, the risk of potential neurodegenerative diseases that the virus has shown to accelerate, such as dementia, is also a big concern. Alzheimer’s is already the fifth leading cause of death for people 65 and older. 

In a recent study of more than 6 million people over the age of 65, Dr. Davis and her team at Case Western found the risk of Alzheimer’s in the year after COVID-19 increased by 50%-80%. The chances were especially high for women older than 85.

To date, there are no good treatments for Alzheimer’s, yet total health care costs for long-term care and hospice services for people with dementia topped $300 billion in 2020. That doesn’t even include the related costs to families.

“The downstream effect of having someone with Alzheimer’s being taken care of by a family member can be devastating on everyone,” she says. “Sometimes the caregivers don’t weather that very well.” 

When Dr. Davis’s own father got Alzheimer’s at age 86, her mother took care of him until she had a stroke one morning while making breakfast. Dr. Davis attributes the stroke to the stress of caregiving. That left Dr. Davis no choice but to seek housing where both her parents could get care. 

Looking at the broader picture, Dr. Davis believes widespread isolation, loneliness, and grief during the pandemic, and the disease of COVID-19 itself, will continue to have a profound impact on psychiatric diagnoses. This in turn could trigger a wave of new substance abuse as a result of unchecked mental health problems.

Still, not all brain experts are jumping to worst-case scenarios, with a lot yet to be understood before sounding the alarm. Joanna Hellmuth, MD, a neurologist and researcher at the University of California, San Francisco, cautions against reading too much into early data, including any assumptions that COVID-19 causes neurodegeneration or irreversible damage in the brain. 

Even with before-and-after brain scans by University of Oxford, England, researchers that show structural changes to the brain after infection, she points out that they didn’t actually study the clinical symptoms of the people in the study, so it’s too soon to reach conclusions about associated cognitive problems.

“It’s an important piece of the puzzle, but we don’t know how that fits together with everything else,” says Dr. Hellmuth. “Some of my patients get better. … I haven’t seen a single person get worse since the pandemic started, and so I’m hopeful.”

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

Weeks after Jeannie Volpe caught COVID-19 in November 2020, she could no longer do her job running sexual assault support groups in Anniston, Ala., because she kept forgetting the details that survivors had shared with her. “People were telling me they were having to revisit their traumatic memories, which isn’t fair to anybody,” the 47-year-old says.

Ms. Volpe has been diagnosed with long-COVID autonomic dysfunction, which includes severe muscle pain, depression, anxiety, and a loss of thinking skills. Some of her symptoms are more commonly known as brain fog, and they’re among the most frequent problems reported by people who have long-term issues after a bout of COVID-19.

Many experts and medical professionals say they haven’t even begun to scratch the surface of what impact this will have in years to come. 

“I’m very worried that we have an epidemic of neurologic dysfunction coming down the pike,” says Pamela Davis, MD, PhD, a research professor at Case Western Reserve University, Cleveland.

In the 2 years Ms. Volpe has been living with long COVID, her executive function – the mental processes that enable people to focus attention, retain information, and multitask – has been so diminished that she had to relearn to drive. One of the various doctors assessing her has suggested speech therapy to help Ms. Volpe relearn how to form words. “I can see the words I want to say in my mind, but I can’t make them come out of my mouth,” she says in a sluggish voice that gives away her condition. 

All of those symptoms make it difficult for her to care for herself. Without a job and health insurance, Ms. Volpe says she’s researched assisted suicide in the states that allow it but has ultimately decided she wants to live. 

“People tell you things like you should be grateful you survived it, and you should; but you shouldn’t expect somebody to not grieve after losing their autonomy, their career, their finances.”

The findings of researchers studying the brain effects of COVID-19 reinforce what people with long COVID have been dealing with from the start. Their experiences aren’t imaginary; they’re consistent with neurological disorders – including myalgic encephalomyelitis, also known as chronic fatigue syndrome, or ME/CFS – which carry much more weight in the public imagination than the term brain fog, which can often be used dismissively.

Studies have found that COVID-19 is linked to conditions such as strokes; seizures; and mood, memory, and movement disorders. 

While there are still a lot of unanswered questions about exactly how COVID-19 affects the brain and what the long-term effects are, there’s enough reason to suggest people should be trying to avoid both infection and reinfection until researchers get more answers.

Worldwide, it’s estimated that COVID-19 has contributed to more than 40 million new cases of neurological disorders, says Ziyad Al-Aly, MD, a clinical epidemiologist and long COVID researcher at Washington University in St. Louis. In his latest study of 14 million medical records of the U.S. Department of Veterans Affairs, the country’s largest integrated health care system, researchers found that regardless of age, gender, race, and lifestyle, people who have had COVID-19 are at a higher risk of getting a wide array of 44 neurological conditions after the first year of infection.

He noted that some of the conditions, such as headaches and mild decline in memory and sharpness, may improve and go away over time. But others that showed up, such as stroke, encephalitis (inflammation of the brain), and Guillain-Barré syndrome (a rare disorder in which the body’s immune system attacks the nerves), often lead to lasting damage. Dr. Al-Aly’s team found that neurological conditions were 7% more likely in those who had COVID-19 than in those who had never been infected. 

What’s more, researchers noticed that compared with control groups, the risk of post-COVID thinking problems was more pronounced in people in their 30s, 40s, and 50s – a group that usually would be very unlikely to have these problems. For those over the age of 60, the risks stood out less because at that stage of life, such thinking problems aren’t as rare.

Another study of the veterans system last year showed that COVID-19 survivors were at a 46% higher risk of considering suicide after 1 year.

“We need to be paying attention to this,” says Dr. Al-Aly.  “What we’ve seen is really the tip of the iceberg.” He worries that millions of people, including youths, will lose out on employment and education while dealing with long-term disabilities – and the economic and societal implications of such a fallout. “What we will all be left with is the aftermath of sheer devastation in some people’s lives,” he says.

Igor Koralnik, MD, chief of neuro-infectious disease and global neurology at Northwestern University, Chicago, has been running a specialized long COVID clinic. His team published a paper in March 2021 detailing what they saw in their first 100 patients. “About half the population in the study missed at least 10 days of work. This is going to have persistent impact on the workforce,” Dr. Koralnik said in a podcast posted on the Northwestern website. “We have seen that not only [do] patients have symptoms, but they have decreased quality of life.”

For older people and their caregivers, the risk of potential neurodegenerative diseases that the virus has shown to accelerate, such as dementia, is also a big concern. Alzheimer’s is already the fifth leading cause of death for people 65 and older. 

In a recent study of more than 6 million people over the age of 65, Dr. Davis and her team at Case Western found the risk of Alzheimer’s in the year after COVID-19 increased by 50%-80%. The chances were especially high for women older than 85.

To date, there are no good treatments for Alzheimer’s, yet total health care costs for long-term care and hospice services for people with dementia topped $300 billion in 2020. That doesn’t even include the related costs to families.

“The downstream effect of having someone with Alzheimer’s being taken care of by a family member can be devastating on everyone,” she says. “Sometimes the caregivers don’t weather that very well.” 

When Dr. Davis’s own father got Alzheimer’s at age 86, her mother took care of him until she had a stroke one morning while making breakfast. Dr. Davis attributes the stroke to the stress of caregiving. That left Dr. Davis no choice but to seek housing where both her parents could get care. 

Looking at the broader picture, Dr. Davis believes widespread isolation, loneliness, and grief during the pandemic, and the disease of COVID-19 itself, will continue to have a profound impact on psychiatric diagnoses. This in turn could trigger a wave of new substance abuse as a result of unchecked mental health problems.

Still, not all brain experts are jumping to worst-case scenarios, with a lot yet to be understood before sounding the alarm. Joanna Hellmuth, MD, a neurologist and researcher at the University of California, San Francisco, cautions against reading too much into early data, including any assumptions that COVID-19 causes neurodegeneration or irreversible damage in the brain. 

Even with before-and-after brain scans by University of Oxford, England, researchers that show structural changes to the brain after infection, she points out that they didn’t actually study the clinical symptoms of the people in the study, so it’s too soon to reach conclusions about associated cognitive problems.

“It’s an important piece of the puzzle, but we don’t know how that fits together with everything else,” says Dr. Hellmuth. “Some of my patients get better. … I haven’t seen a single person get worse since the pandemic started, and so I’m hopeful.”

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

Weeks after Jeannie Volpe caught COVID-19 in November 2020, she could no longer do her job running sexual assault support groups in Anniston, Ala., because she kept forgetting the details that survivors had shared with her. “People were telling me they were having to revisit their traumatic memories, which isn’t fair to anybody,” the 47-year-old says.

Ms. Volpe has been diagnosed with long-COVID autonomic dysfunction, which includes severe muscle pain, depression, anxiety, and a loss of thinking skills. Some of her symptoms are more commonly known as brain fog, and they’re among the most frequent problems reported by people who have long-term issues after a bout of COVID-19.

Many experts and medical professionals say they haven’t even begun to scratch the surface of what impact this will have in years to come. 

“I’m very worried that we have an epidemic of neurologic dysfunction coming down the pike,” says Pamela Davis, MD, PhD, a research professor at Case Western Reserve University, Cleveland.

In the 2 years Ms. Volpe has been living with long COVID, her executive function – the mental processes that enable people to focus attention, retain information, and multitask – has been so diminished that she had to relearn to drive. One of the various doctors assessing her has suggested speech therapy to help Ms. Volpe relearn how to form words. “I can see the words I want to say in my mind, but I can’t make them come out of my mouth,” she says in a sluggish voice that gives away her condition. 

All of those symptoms make it difficult for her to care for herself. Without a job and health insurance, Ms. Volpe says she’s researched assisted suicide in the states that allow it but has ultimately decided she wants to live. 

“People tell you things like you should be grateful you survived it, and you should; but you shouldn’t expect somebody to not grieve after losing their autonomy, their career, their finances.”

The findings of researchers studying the brain effects of COVID-19 reinforce what people with long COVID have been dealing with from the start. Their experiences aren’t imaginary; they’re consistent with neurological disorders – including myalgic encephalomyelitis, also known as chronic fatigue syndrome, or ME/CFS – which carry much more weight in the public imagination than the term brain fog, which can often be used dismissively.

Studies have found that COVID-19 is linked to conditions such as strokes; seizures; and mood, memory, and movement disorders. 

While there are still a lot of unanswered questions about exactly how COVID-19 affects the brain and what the long-term effects are, there’s enough reason to suggest people should be trying to avoid both infection and reinfection until researchers get more answers.

Worldwide, it’s estimated that COVID-19 has contributed to more than 40 million new cases of neurological disorders, says Ziyad Al-Aly, MD, a clinical epidemiologist and long COVID researcher at Washington University in St. Louis. In his latest study of 14 million medical records of the U.S. Department of Veterans Affairs, the country’s largest integrated health care system, researchers found that regardless of age, gender, race, and lifestyle, people who have had COVID-19 are at a higher risk of getting a wide array of 44 neurological conditions after the first year of infection.

He noted that some of the conditions, such as headaches and mild decline in memory and sharpness, may improve and go away over time. But others that showed up, such as stroke, encephalitis (inflammation of the brain), and Guillain-Barré syndrome (a rare disorder in which the body’s immune system attacks the nerves), often lead to lasting damage. Dr. Al-Aly’s team found that neurological conditions were 7% more likely in those who had COVID-19 than in those who had never been infected. 

What’s more, researchers noticed that compared with control groups, the risk of post-COVID thinking problems was more pronounced in people in their 30s, 40s, and 50s – a group that usually would be very unlikely to have these problems. For those over the age of 60, the risks stood out less because at that stage of life, such thinking problems aren’t as rare.

Another study of the veterans system last year showed that COVID-19 survivors were at a 46% higher risk of considering suicide after 1 year.

“We need to be paying attention to this,” says Dr. Al-Aly.  “What we’ve seen is really the tip of the iceberg.” He worries that millions of people, including youths, will lose out on employment and education while dealing with long-term disabilities – and the economic and societal implications of such a fallout. “What we will all be left with is the aftermath of sheer devastation in some people’s lives,” he says.

Igor Koralnik, MD, chief of neuro-infectious disease and global neurology at Northwestern University, Chicago, has been running a specialized long COVID clinic. His team published a paper in March 2021 detailing what they saw in their first 100 patients. “About half the population in the study missed at least 10 days of work. This is going to have persistent impact on the workforce,” Dr. Koralnik said in a podcast posted on the Northwestern website. “We have seen that not only [do] patients have symptoms, but they have decreased quality of life.”

For older people and their caregivers, the risk of potential neurodegenerative diseases that the virus has shown to accelerate, such as dementia, is also a big concern. Alzheimer’s is already the fifth leading cause of death for people 65 and older. 

In a recent study of more than 6 million people over the age of 65, Dr. Davis and her team at Case Western found the risk of Alzheimer’s in the year after COVID-19 increased by 50%-80%. The chances were especially high for women older than 85.

To date, there are no good treatments for Alzheimer’s, yet total health care costs for long-term care and hospice services for people with dementia topped $300 billion in 2020. That doesn’t even include the related costs to families.

“The downstream effect of having someone with Alzheimer’s being taken care of by a family member can be devastating on everyone,” she says. “Sometimes the caregivers don’t weather that very well.” 

When Dr. Davis’s own father got Alzheimer’s at age 86, her mother took care of him until she had a stroke one morning while making breakfast. Dr. Davis attributes the stroke to the stress of caregiving. That left Dr. Davis no choice but to seek housing where both her parents could get care. 

Looking at the broader picture, Dr. Davis believes widespread isolation, loneliness, and grief during the pandemic, and the disease of COVID-19 itself, will continue to have a profound impact on psychiatric diagnoses. This in turn could trigger a wave of new substance abuse as a result of unchecked mental health problems.

Still, not all brain experts are jumping to worst-case scenarios, with a lot yet to be understood before sounding the alarm. Joanna Hellmuth, MD, a neurologist and researcher at the University of California, San Francisco, cautions against reading too much into early data, including any assumptions that COVID-19 causes neurodegeneration or irreversible damage in the brain. 

Even with before-and-after brain scans by University of Oxford, England, researchers that show structural changes to the brain after infection, she points out that they didn’t actually study the clinical symptoms of the people in the study, so it’s too soon to reach conclusions about associated cognitive problems.

“It’s an important piece of the puzzle, but we don’t know how that fits together with everything else,” says Dr. Hellmuth. “Some of my patients get better. … I haven’t seen a single person get worse since the pandemic started, and so I’m hopeful.”

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

The American College of Cardiology has released an Expert Consensus Decision Pathway on the evaluation and disposition of acute chest pain in the emergency department.

Chest pain accounts for more than 7 million ED visits annually. A major challenge is to quickly identify the small number of patients with acute coronary syndrome (ACS) among the large number of patients who have noncardiac conditions.

The new document is intended to provide guidance on how to “practically apply” recommendations from the 2021 American Heart Association/American College of Cardiology Guideline for the Evaluation and Diagnosis of Chest Pain, focusing specifically on patients who present to the ED, the writing group explains.

“A systematic approach – both at the level of the institution and the individual patient – is essential to achieve optimal outcomes for patients presenting with chest pain to the ED,” say writing group chair Michael Kontos, MD, Virginia Commonwealth University, Richmond, and colleagues.

At the institution level, this decision pathway recommends high-sensitivity cardiac troponin (hs-cTn) assays coupled with a clinical decision pathway (CDP) to reduce ED “dwell” times and increase the number of patients with chest pain who can safely be discharged without additional testing. This will decrease ED crowding and limit unnecessary testing, they point out. 

At the individual patient level, this document aims to provide structure for the ED evaluation of chest pain, accelerating the evaluation process and matching the intensity of testing and treatment to patient risk.

The 36-page document was published online in the Journal of the American College of Cardiology.

Key summary points in the document include the following:

• Electrocardiogram remains the best initial test for evaluation of chest pain in the ED and should be performed and interpreted within 10 minutes of ED arrival.
• In patients who arrive via ambulance, the prehospital ECG should be reviewed, because ischemic changes may have resolved before ED arrival.
• When the ECG shows evidence of acute infarction or ischemia, subsequent care should follow current guidelines for management of acute ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation ACS (NSTE-ACS).
• Patients with a nonischemic ECG can enter an accelerated CDP designed to provide rapid risk assessment and exclusion of ACS.
• Patients who are hemodynamically unstable, have significant arrhythmias, or evidence of significant heart failure should be evaluated and treated appropriately and are not candidates for an accelerated CDP.
• High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) are the preferred biomarkers for evaluation of possible ACS.
• Patients classified as low risk (rule out) using the current hs-cTn-based CDPs can generally be discharged directly from the ED without additional testing, although outpatient testing may be considered in selected cases.
• Patients with substantially elevated initial hs-cTn values or those with significant dynamic changes over 1-3 hours are assigned to the abnormal/high-risk category and should be further classified according to the universal definition of myocardial infarction type 1 or 2 or acute or chronic nonischemic cardiac injury.
• High-risk patients should usually be admitted to an inpatient setting for further evaluation and treatment.
• Patients determined to be intermediate risk with the CDP should undergo additional observation with repeat hs-cTn measurements at 3-6 hours and risk assessment using either the modified HEART (history, ECG, age, risk factors, and troponin) score or the ED assessment of chest pain score (EDACS).
• Noninvasive testing should be considered for the intermediate-risk group unless low-risk features are identified using risk scores or noninvasive testing has been performed recently with normal or low-risk findings.

The writing group notes that “safe and efficient” management of chest pain in the ED requires appropriate follow-up after discharge. Timing of follow-up and referral for outpatient noninvasive testing should be influenced by patient risk and results of cardiac testing.

Disclosures for members of the writing group are available with the original article.

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

The American College of Cardiology has released an Expert Consensus Decision Pathway on the evaluation and disposition of acute chest pain in the emergency department.

Chest pain accounts for more than 7 million ED visits annually. A major challenge is to quickly identify the small number of patients with acute coronary syndrome (ACS) among the large number of patients who have noncardiac conditions.

The new document is intended to provide guidance on how to “practically apply” recommendations from the 2021 American Heart Association/American College of Cardiology Guideline for the Evaluation and Diagnosis of Chest Pain, focusing specifically on patients who present to the ED, the writing group explains.

“A systematic approach – both at the level of the institution and the individual patient – is essential to achieve optimal outcomes for patients presenting with chest pain to the ED,” say writing group chair Michael Kontos, MD, Virginia Commonwealth University, Richmond, and colleagues.

At the institution level, this decision pathway recommends high-sensitivity cardiac troponin (hs-cTn) assays coupled with a clinical decision pathway (CDP) to reduce ED “dwell” times and increase the number of patients with chest pain who can safely be discharged without additional testing. This will decrease ED crowding and limit unnecessary testing, they point out. 

At the individual patient level, this document aims to provide structure for the ED evaluation of chest pain, accelerating the evaluation process and matching the intensity of testing and treatment to patient risk.

The 36-page document was published online in the Journal of the American College of Cardiology.

Key summary points in the document include the following:

• Electrocardiogram remains the best initial test for evaluation of chest pain in the ED and should be performed and interpreted within 10 minutes of ED arrival.
• In patients who arrive via ambulance, the prehospital ECG should be reviewed, because ischemic changes may have resolved before ED arrival.
• When the ECG shows evidence of acute infarction or ischemia, subsequent care should follow current guidelines for management of acute ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation ACS (NSTE-ACS).
• Patients with a nonischemic ECG can enter an accelerated CDP designed to provide rapid risk assessment and exclusion of ACS.
• Patients who are hemodynamically unstable, have significant arrhythmias, or evidence of significant heart failure should be evaluated and treated appropriately and are not candidates for an accelerated CDP.
• High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) are the preferred biomarkers for evaluation of possible ACS.
• Patients classified as low risk (rule out) using the current hs-cTn-based CDPs can generally be discharged directly from the ED without additional testing, although outpatient testing may be considered in selected cases.
• Patients with substantially elevated initial hs-cTn values or those with significant dynamic changes over 1-3 hours are assigned to the abnormal/high-risk category and should be further classified according to the universal definition of myocardial infarction type 1 or 2 or acute or chronic nonischemic cardiac injury.
• High-risk patients should usually be admitted to an inpatient setting for further evaluation and treatment.
• Patients determined to be intermediate risk with the CDP should undergo additional observation with repeat hs-cTn measurements at 3-6 hours and risk assessment using either the modified HEART (history, ECG, age, risk factors, and troponin) score or the ED assessment of chest pain score (EDACS).
• Noninvasive testing should be considered for the intermediate-risk group unless low-risk features are identified using risk scores or noninvasive testing has been performed recently with normal or low-risk findings.

The writing group notes that “safe and efficient” management of chest pain in the ED requires appropriate follow-up after discharge. Timing of follow-up and referral for outpatient noninvasive testing should be influenced by patient risk and results of cardiac testing.

Disclosures for members of the writing group are available with the original article.

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

The American College of Cardiology has released an Expert Consensus Decision Pathway on the evaluation and disposition of acute chest pain in the emergency department.

Chest pain accounts for more than 7 million ED visits annually. A major challenge is to quickly identify the small number of patients with acute coronary syndrome (ACS) among the large number of patients who have noncardiac conditions.

The new document is intended to provide guidance on how to “practically apply” recommendations from the 2021 American Heart Association/American College of Cardiology Guideline for the Evaluation and Diagnosis of Chest Pain, focusing specifically on patients who present to the ED, the writing group explains.

“A systematic approach – both at the level of the institution and the individual patient – is essential to achieve optimal outcomes for patients presenting with chest pain to the ED,” say writing group chair Michael Kontos, MD, Virginia Commonwealth University, Richmond, and colleagues.

At the institution level, this decision pathway recommends high-sensitivity cardiac troponin (hs-cTn) assays coupled with a clinical decision pathway (CDP) to reduce ED “dwell” times and increase the number of patients with chest pain who can safely be discharged without additional testing. This will decrease ED crowding and limit unnecessary testing, they point out. 

At the individual patient level, this document aims to provide structure for the ED evaluation of chest pain, accelerating the evaluation process and matching the intensity of testing and treatment to patient risk.

The 36-page document was published online in the Journal of the American College of Cardiology.

Key summary points in the document include the following:

• Electrocardiogram remains the best initial test for evaluation of chest pain in the ED and should be performed and interpreted within 10 minutes of ED arrival.
• In patients who arrive via ambulance, the prehospital ECG should be reviewed, because ischemic changes may have resolved before ED arrival.
• When the ECG shows evidence of acute infarction or ischemia, subsequent care should follow current guidelines for management of acute ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation ACS (NSTE-ACS).
• Patients with a nonischemic ECG can enter an accelerated CDP designed to provide rapid risk assessment and exclusion of ACS.
• Patients who are hemodynamically unstable, have significant arrhythmias, or evidence of significant heart failure should be evaluated and treated appropriately and are not candidates for an accelerated CDP.
• High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) are the preferred biomarkers for evaluation of possible ACS.
• Patients classified as low risk (rule out) using the current hs-cTn-based CDPs can generally be discharged directly from the ED without additional testing, although outpatient testing may be considered in selected cases.
• Patients with substantially elevated initial hs-cTn values or those with significant dynamic changes over 1-3 hours are assigned to the abnormal/high-risk category and should be further classified according to the universal definition of myocardial infarction type 1 or 2 or acute or chronic nonischemic cardiac injury.
• High-risk patients should usually be admitted to an inpatient setting for further evaluation and treatment.
• Patients determined to be intermediate risk with the CDP should undergo additional observation with repeat hs-cTn measurements at 3-6 hours and risk assessment using either the modified HEART (history, ECG, age, risk factors, and troponin) score or the ED assessment of chest pain score (EDACS).
• Noninvasive testing should be considered for the intermediate-risk group unless low-risk features are identified using risk scores or noninvasive testing has been performed recently with normal or low-risk findings.

The writing group notes that “safe and efficient” management of chest pain in the ED requires appropriate follow-up after discharge. Timing of follow-up and referral for outpatient noninvasive testing should be influenced by patient risk and results of cardiac testing.

Disclosures for members of the writing group are available with the original article.

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

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.