Transrectal ultrasonography–guided needle biopsy of the prostate confirms a diagnosis of metastatic prostate cancer. 

With the exception of nonmelanoma skin cancer, prostate cancer is the most commonly occurring cancer and the second most common cause of cancer-associated mortality in men in the United States. Most patients have localized stage at diagnosis; however, the incidence of distant-stage prostate cancer at diagnosis is steadily increasing. Five-year survival for distant-stage prostate cancer is approximately 32%. 

High serum levels of PSA have been associated with bone metastases in men with prostate cancer, and the presence of metastatic disease increases with rising PSA levels. Over the past several decades, PSA levels > 100 ng/mL have been used as a marker for metastatic prostate cancer. However, not all men with metastatic prostate cancer will have elevated PSA levels, and bone imaging is necessary for correct staging and treatment stratification. 

Bone metastases occur in approximately 70% of men with advanced prostate cancer, most often in the spine, and are a leading cause of morbidity and mortality. Bone metastases can cause severe pain, particularly in the evening; decreased mobility; pathologic fractures; spinal cord compression; bone marrow aplasia; and hypercalcemia.
 
The bone marrow represents a fertile soil into which prostate tumors can colonize and proliferate. Such colonization by prostate tumor cells is commonly associated with tumor-induced bone lesions, which typically arise from an imbalance between bone-forming osteoblasts and bone-absorbing osteoclasts generated by prostate cancer cells. Whereas most solid tumors, such as breast cancer and melanoma, have a propensity for causing osteolytic lesions with excessive bone resorption, bone lesions resulting from prostate cancer are largely osteoblastic and are associated with uncontrolled low-quality bone formation. The resultant metastases have a unique bone formation that can be detected by plain radiography, bone scan, bone biopsy, and increased serum alkaline phosphatase levels. 

CT; skeletal scintigraphy and PET; and single-photon emission CT (SPECT)/CT, PET/CT, and PET/MRI are recommended diagnostics for men at risk for prostate cancer metastasis. Radiotracer-based PET, which mainly uses altered metabolic activity or explicitly overexpressed receptors, is a promising diagnostic modality. However, the choice of a respective radiotracer must be carefully considered because a single radiotracer is typically insufficient to visualize all clinical stages of prostate cancer. In addition, its use is reliant on the extent of malignant tissue, tumor heterogeneity, and previous treatments. 

Systemic androgen-deprivation therapy, with or without docetaxel-based chemotherapy, is the standard of care for metastatic prostate cancer. Treatment is largely directed at preventing skeletal-related events and providing pain management. 

Radium-223 is the only available therapy for castrate-resistant prostate cancer that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. Based on the results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for castrate-resistant prostate cancer with bone lesions. 

The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.

Kyle A. Richards, MD, has disclosed no relevant financial relationships.

Transrectal ultrasonography–guided needle biopsy of the prostate confirms a diagnosis of metastatic prostate cancer. 

With the exception of nonmelanoma skin cancer, prostate cancer is the most commonly occurring cancer and the second most common cause of cancer-associated mortality in men in the United States. Most patients have localized stage at diagnosis; however, the incidence of distant-stage prostate cancer at diagnosis is steadily increasing. Five-year survival for distant-stage prostate cancer is approximately 32%. 

High serum levels of PSA have been associated with bone metastases in men with prostate cancer, and the presence of metastatic disease increases with rising PSA levels. Over the past several decades, PSA levels > 100 ng/mL have been used as a marker for metastatic prostate cancer. However, not all men with metastatic prostate cancer will have elevated PSA levels, and bone imaging is necessary for correct staging and treatment stratification. 

Bone metastases occur in approximately 70% of men with advanced prostate cancer, most often in the spine, and are a leading cause of morbidity and mortality. Bone metastases can cause severe pain, particularly in the evening; decreased mobility; pathologic fractures; spinal cord compression; bone marrow aplasia; and hypercalcemia.
 
The bone marrow represents a fertile soil into which prostate tumors can colonize and proliferate. Such colonization by prostate tumor cells is commonly associated with tumor-induced bone lesions, which typically arise from an imbalance between bone-forming osteoblasts and bone-absorbing osteoclasts generated by prostate cancer cells. Whereas most solid tumors, such as breast cancer and melanoma, have a propensity for causing osteolytic lesions with excessive bone resorption, bone lesions resulting from prostate cancer are largely osteoblastic and are associated with uncontrolled low-quality bone formation. The resultant metastases have a unique bone formation that can be detected by plain radiography, bone scan, bone biopsy, and increased serum alkaline phosphatase levels. 

CT; skeletal scintigraphy and PET; and single-photon emission CT (SPECT)/CT, PET/CT, and PET/MRI are recommended diagnostics for men at risk for prostate cancer metastasis. Radiotracer-based PET, which mainly uses altered metabolic activity or explicitly overexpressed receptors, is a promising diagnostic modality. However, the choice of a respective radiotracer must be carefully considered because a single radiotracer is typically insufficient to visualize all clinical stages of prostate cancer. In addition, its use is reliant on the extent of malignant tissue, tumor heterogeneity, and previous treatments. 

Systemic androgen-deprivation therapy, with or without docetaxel-based chemotherapy, is the standard of care for metastatic prostate cancer. Treatment is largely directed at preventing skeletal-related events and providing pain management. 

Radium-223 is the only available therapy for castrate-resistant prostate cancer that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. Based on the results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for castrate-resistant prostate cancer with bone lesions. 

The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.

Kyle A. Richards, MD, has disclosed no relevant financial relationships.

Transrectal ultrasonography–guided needle biopsy of the prostate confirms a diagnosis of metastatic prostate cancer. 

With the exception of nonmelanoma skin cancer, prostate cancer is the most commonly occurring cancer and the second most common cause of cancer-associated mortality in men in the United States. Most patients have localized stage at diagnosis; however, the incidence of distant-stage prostate cancer at diagnosis is steadily increasing. Five-year survival for distant-stage prostate cancer is approximately 32%. 

High serum levels of PSA have been associated with bone metastases in men with prostate cancer, and the presence of metastatic disease increases with rising PSA levels. Over the past several decades, PSA levels > 100 ng/mL have been used as a marker for metastatic prostate cancer. However, not all men with metastatic prostate cancer will have elevated PSA levels, and bone imaging is necessary for correct staging and treatment stratification. 

Bone metastases occur in approximately 70% of men with advanced prostate cancer, most often in the spine, and are a leading cause of morbidity and mortality. Bone metastases can cause severe pain, particularly in the evening; decreased mobility; pathologic fractures; spinal cord compression; bone marrow aplasia; and hypercalcemia.
 
The bone marrow represents a fertile soil into which prostate tumors can colonize and proliferate. Such colonization by prostate tumor cells is commonly associated with tumor-induced bone lesions, which typically arise from an imbalance between bone-forming osteoblasts and bone-absorbing osteoclasts generated by prostate cancer cells. Whereas most solid tumors, such as breast cancer and melanoma, have a propensity for causing osteolytic lesions with excessive bone resorption, bone lesions resulting from prostate cancer are largely osteoblastic and are associated with uncontrolled low-quality bone formation. The resultant metastases have a unique bone formation that can be detected by plain radiography, bone scan, bone biopsy, and increased serum alkaline phosphatase levels. 

CT; skeletal scintigraphy and PET; and single-photon emission CT (SPECT)/CT, PET/CT, and PET/MRI are recommended diagnostics for men at risk for prostate cancer metastasis. Radiotracer-based PET, which mainly uses altered metabolic activity or explicitly overexpressed receptors, is a promising diagnostic modality. However, the choice of a respective radiotracer must be carefully considered because a single radiotracer is typically insufficient to visualize all clinical stages of prostate cancer. In addition, its use is reliant on the extent of malignant tissue, tumor heterogeneity, and previous treatments. 

Systemic androgen-deprivation therapy, with or without docetaxel-based chemotherapy, is the standard of care for metastatic prostate cancer. Treatment is largely directed at preventing skeletal-related events and providing pain management. 

Radium-223 is the only available therapy for castrate-resistant prostate cancer that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. Based on the results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for castrate-resistant prostate cancer with bone lesions. 

The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.

Kyle A. Richards, MD, has disclosed no relevant financial relationships.

Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.

Jasmina007/Getty Images

Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.

At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.

Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.

“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.

“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.

The study was published online May 20 in Human Animal Interaction Bulletin.


 

Everyday interactions

An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.

Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.

ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.

There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.

Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).

Six participants adopted a cat, and five adopted a dog.

Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.

Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
 

Motivation, comfort, calm

The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.

For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.

A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.

Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.

Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.

The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.

Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.

“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
 

Postpandemic mental health

Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.

“We need to educate ourselves about what other options are available to provide symptomatic relief for patients besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.

The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
 

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

Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.

Jasmina007/Getty Images

Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.

At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.

Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.

“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.

“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.

The study was published online May 20 in Human Animal Interaction Bulletin.


 

Everyday interactions

An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.

Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.

ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.

There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.

Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).

Six participants adopted a cat, and five adopted a dog.

Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.

Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
 

Motivation, comfort, calm

The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.

For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.

A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.

Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.

Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.

The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.

Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.

“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
 

Postpandemic mental health

Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.

“We need to educate ourselves about what other options are available to provide symptomatic relief for patients besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.

The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
 

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

Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.

Jasmina007/Getty Images

Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.

At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.

Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.

“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.

“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.

The study was published online May 20 in Human Animal Interaction Bulletin.


 

Everyday interactions

An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.

Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.

ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.

There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.

Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).

Six participants adopted a cat, and five adopted a dog.

Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.

Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
 

Motivation, comfort, calm

The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.

For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.

A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.

Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.

Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.

The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.

Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.

“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
 

Postpandemic mental health

Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.

“We need to educate ourselves about what other options are available to provide symptomatic relief for patients besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.

The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
 

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

Background: In the final year before death, surgery is common for many patients. Prior studies have shown that fewer than 38% of surgical patients receive palliative care services before death. Palliative care involvement has been shown to improve quality of life and coordination of care in surgical patients.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: In the final year before death, surgery is common for many patients. Prior studies have shown that fewer than 38% of surgical patients receive palliative care services before death. Palliative care involvement has been shown to improve quality of life and coordination of care in surgical patients.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: In the final year before death, surgery is common for many patients. Prior studies have shown that fewer than 38% of surgical patients receive palliative care services before death. Palliative care involvement has been shown to improve quality of life and coordination of care in surgical patients.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

[email protected]

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

[email protected]

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

[email protected]

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

[email protected]

The keys to effective resuscitation in the hospital setting include effective compression and early defibrillation, according to Jessica Nave Allen, MD, FHM, a hospitalist with Emory University Hospital in Atlanta. She spoke about best practices in resuscitation medicine recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

“We know CPR [cardiopulmonary resuscitation] and shocking are the two biggest determinants of outcomes, so really strive to make those chest compressions really high quality,” said Dr. Allen. She urged hospitalists to consider mechanical piston compressions and even “reverse CPR” when appropriate.

Dr. Allen offered several other tips about effective in-hospital resuscitation.
 

Don’t overcrowd the hospital room

There shouldn’t be more than eight people inside the room during a code, she said. If you’re the code leader, “make sure that somebody has already started high-quality chest compressions. You want to make sure that somebody is already on the airway. It’s usually two people, one person to actually hold the mask down to make sure there’s a good seal, and the other person to deliver the breaths.”

Two to three people should be assigned to chest compressions, Dr. Allen said, “and you need one or two nurses for medication delivery and grabbing things from the runners. And then you need to have a recorder and the code leader. Everyone else who’s not in one of those formalized roles needs to be outside the room. That includes the pharmacist, who usually stands at the door if you don’t have a code pharmacist at your institution.”

A helpful mnemonic for the resuscitation process is I(CA)RAMBO, which was developed at Tufts Medical Center and published in 2020, she said. The mnemonic stands for the following:

• I: Identify yourself as code leader.
• CA: Compression, Airway.
• R: Roles (assign roles in the resuscitation).
• A: Access (intravenous access is preferred to intraosseous, per the American Heart Association’s , unless intravenous access is unavailable, Dr. Allen noted).
• M: Monitor (make sure pads are placed correctly; turn the defibrillator on).
• B: Backboard.
• O: Oxygen.

Focus on high-quality chest compressions

The number of chest compressions must be 100-120 per minute, Dr. Allen said. You can time them to the beat of a song, such as “Stayin’ Alive,” or with a metronome, she said, “but whatever it is, you need to stay in that window.”

The correct compression depth is 2-2.4 inches. “That’s very difficult to do during the middle of a code, which is why it’s important to allow full recoil,” she said. “This doesn’t mean taking your hands off of the chest: You should actually never take your hands off of the chest. But you should allow the chest wall to return to its normal state. Also, make sure you aren’t off the chest for more for 10 seconds whenever you’re doing a rhythm check.”

Audiovisual feedback devices can provide insight into the quality of chest compressions. For example, some defibrillators are equipped with sensors that urge users to push harder and faster when appropriate. “Studies have shown that the quality of chest compressions goes up when you use these devices,” she said.
 

Don’t be afraid of mechanical chest compression

Although early research raised questions about the quality of resuscitation outcomes when mechanical piston chest compression devices are used, a 2015 systematic review and meta-analysis found that “man was equal to machine,” Dr. Allen said. “The bottom line is that these devices may be a reasonable alternative to conventional CPR in specific settings.”

American Heart Association guidelines state that mechanical compressions may be appropriate in certain specific situations “where the delivery of high-quality manual compressions may be challenging or dangerous for the provider.”

According to Dr. Allen, “there are times when it’s useful,” such as for a patient with COVID-19, in the cath lab, or in a medical helicopter.
 

Move quickly to defibrillation

“Most of us know that you want to shock as early as possible in shockable rhythms,” Dr. Allen said. Support, she said, comes from a 2008 study that linked delayed defibrillation to lower survival rates. “We want to shock as soon as possible, because your chances of surviving go down for every minute you wait.”

Take special care for patients with confirmed or suspected COVID-19

“Not surprisingly, the goals here are to minimize exposure to staff,” Dr. Allen said.

Put on personal protective equipment before entering the room even if care is delayed, she advised, and reduce the number of staff members in the room below the typical maximum of eight. “In COVID, it should be a maximum of six, and some institutions have even gotten it down to four where the code leaders are outside the room with an iPad.”

Use mechanical compression devices, she advised, and place patients on ventilators as soon as possible. She added: “Use a HEPA [high-efficiency particulate air] filter for all your airway modalities.”

CPR may be challenging in some cases, such as when a large, intubated patient is prone and cannot be quickly or safely flipped over. In those cases, consider posterior chest compressions, also known as reverse CPR, at vertebral positions T7-T10. “We have done reverse CPR on several COVID patients throughout the Emory system,” she said.
 

Debrief right after codes

“You really want to debrief with the code team,” Dr. Allen said. “If you don’t already have a policy in place at your institution, you should help come up with one where you sit down with the team and talk about what could you have done better as a group. It’s not a time to place blame. It’s a time to learn.”

Dr. Allen has disclosed no relevant financial relationships.

This article was updated 7/26/21.

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

The keys to effective resuscitation in the hospital setting include effective compression and early defibrillation, according to Jessica Nave Allen, MD, FHM, a hospitalist with Emory University Hospital in Atlanta. She spoke about best practices in resuscitation medicine recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

“We know CPR [cardiopulmonary resuscitation] and shocking are the two biggest determinants of outcomes, so really strive to make those chest compressions really high quality,” said Dr. Allen. She urged hospitalists to consider mechanical piston compressions and even “reverse CPR” when appropriate.

Dr. Allen offered several other tips about effective in-hospital resuscitation.
 

Don’t overcrowd the hospital room

There shouldn’t be more than eight people inside the room during a code, she said. If you’re the code leader, “make sure that somebody has already started high-quality chest compressions. You want to make sure that somebody is already on the airway. It’s usually two people, one person to actually hold the mask down to make sure there’s a good seal, and the other person to deliver the breaths.”

Two to three people should be assigned to chest compressions, Dr. Allen said, “and you need one or two nurses for medication delivery and grabbing things from the runners. And then you need to have a recorder and the code leader. Everyone else who’s not in one of those formalized roles needs to be outside the room. That includes the pharmacist, who usually stands at the door if you don’t have a code pharmacist at your institution.”

A helpful mnemonic for the resuscitation process is I(CA)RAMBO, which was developed at Tufts Medical Center and published in 2020, she said. The mnemonic stands for the following:

• I: Identify yourself as code leader.
• CA: Compression, Airway.
• R: Roles (assign roles in the resuscitation).
• A: Access (intravenous access is preferred to intraosseous, per the American Heart Association’s , unless intravenous access is unavailable, Dr. Allen noted).
• M: Monitor (make sure pads are placed correctly; turn the defibrillator on).
• B: Backboard.
• O: Oxygen.

Focus on high-quality chest compressions

The number of chest compressions must be 100-120 per minute, Dr. Allen said. You can time them to the beat of a song, such as “Stayin’ Alive,” or with a metronome, she said, “but whatever it is, you need to stay in that window.”

The correct compression depth is 2-2.4 inches. “That’s very difficult to do during the middle of a code, which is why it’s important to allow full recoil,” she said. “This doesn’t mean taking your hands off of the chest: You should actually never take your hands off of the chest. But you should allow the chest wall to return to its normal state. Also, make sure you aren’t off the chest for more for 10 seconds whenever you’re doing a rhythm check.”

Audiovisual feedback devices can provide insight into the quality of chest compressions. For example, some defibrillators are equipped with sensors that urge users to push harder and faster when appropriate. “Studies have shown that the quality of chest compressions goes up when you use these devices,” she said.
 

Don’t be afraid of mechanical chest compression

Although early research raised questions about the quality of resuscitation outcomes when mechanical piston chest compression devices are used, a 2015 systematic review and meta-analysis found that “man was equal to machine,” Dr. Allen said. “The bottom line is that these devices may be a reasonable alternative to conventional CPR in specific settings.”

American Heart Association guidelines state that mechanical compressions may be appropriate in certain specific situations “where the delivery of high-quality manual compressions may be challenging or dangerous for the provider.”

According to Dr. Allen, “there are times when it’s useful,” such as for a patient with COVID-19, in the cath lab, or in a medical helicopter.
 

Move quickly to defibrillation

“Most of us know that you want to shock as early as possible in shockable rhythms,” Dr. Allen said. Support, she said, comes from a 2008 study that linked delayed defibrillation to lower survival rates. “We want to shock as soon as possible, because your chances of surviving go down for every minute you wait.”

Take special care for patients with confirmed or suspected COVID-19

“Not surprisingly, the goals here are to minimize exposure to staff,” Dr. Allen said.

Put on personal protective equipment before entering the room even if care is delayed, she advised, and reduce the number of staff members in the room below the typical maximum of eight. “In COVID, it should be a maximum of six, and some institutions have even gotten it down to four where the code leaders are outside the room with an iPad.”

Use mechanical compression devices, she advised, and place patients on ventilators as soon as possible. She added: “Use a HEPA [high-efficiency particulate air] filter for all your airway modalities.”

CPR may be challenging in some cases, such as when a large, intubated patient is prone and cannot be quickly or safely flipped over. In those cases, consider posterior chest compressions, also known as reverse CPR, at vertebral positions T7-T10. “We have done reverse CPR on several COVID patients throughout the Emory system,” she said.
 

Debrief right after codes

“You really want to debrief with the code team,” Dr. Allen said. “If you don’t already have a policy in place at your institution, you should help come up with one where you sit down with the team and talk about what could you have done better as a group. It’s not a time to place blame. It’s a time to learn.”

Dr. Allen has disclosed no relevant financial relationships.

This article was updated 7/26/21.

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

The keys to effective resuscitation in the hospital setting include effective compression and early defibrillation, according to Jessica Nave Allen, MD, FHM, a hospitalist with Emory University Hospital in Atlanta. She spoke about best practices in resuscitation medicine recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

“We know CPR [cardiopulmonary resuscitation] and shocking are the two biggest determinants of outcomes, so really strive to make those chest compressions really high quality,” said Dr. Allen. She urged hospitalists to consider mechanical piston compressions and even “reverse CPR” when appropriate.

Dr. Allen offered several other tips about effective in-hospital resuscitation.
 

Don’t overcrowd the hospital room

There shouldn’t be more than eight people inside the room during a code, she said. If you’re the code leader, “make sure that somebody has already started high-quality chest compressions. You want to make sure that somebody is already on the airway. It’s usually two people, one person to actually hold the mask down to make sure there’s a good seal, and the other person to deliver the breaths.”

Two to three people should be assigned to chest compressions, Dr. Allen said, “and you need one or two nurses for medication delivery and grabbing things from the runners. And then you need to have a recorder and the code leader. Everyone else who’s not in one of those formalized roles needs to be outside the room. That includes the pharmacist, who usually stands at the door if you don’t have a code pharmacist at your institution.”

A helpful mnemonic for the resuscitation process is I(CA)RAMBO, which was developed at Tufts Medical Center and published in 2020, she said. The mnemonic stands for the following:

• I: Identify yourself as code leader.
• CA: Compression, Airway.
• R: Roles (assign roles in the resuscitation).
• A: Access (intravenous access is preferred to intraosseous, per the American Heart Association’s , unless intravenous access is unavailable, Dr. Allen noted).
• M: Monitor (make sure pads are placed correctly; turn the defibrillator on).
• B: Backboard.
• O: Oxygen.

Focus on high-quality chest compressions

The number of chest compressions must be 100-120 per minute, Dr. Allen said. You can time them to the beat of a song, such as “Stayin’ Alive,” or with a metronome, she said, “but whatever it is, you need to stay in that window.”

The correct compression depth is 2-2.4 inches. “That’s very difficult to do during the middle of a code, which is why it’s important to allow full recoil,” she said. “This doesn’t mean taking your hands off of the chest: You should actually never take your hands off of the chest. But you should allow the chest wall to return to its normal state. Also, make sure you aren’t off the chest for more for 10 seconds whenever you’re doing a rhythm check.”

Audiovisual feedback devices can provide insight into the quality of chest compressions. For example, some defibrillators are equipped with sensors that urge users to push harder and faster when appropriate. “Studies have shown that the quality of chest compressions goes up when you use these devices,” she said.
 

Don’t be afraid of mechanical chest compression

Although early research raised questions about the quality of resuscitation outcomes when mechanical piston chest compression devices are used, a 2015 systematic review and meta-analysis found that “man was equal to machine,” Dr. Allen said. “The bottom line is that these devices may be a reasonable alternative to conventional CPR in specific settings.”

American Heart Association guidelines state that mechanical compressions may be appropriate in certain specific situations “where the delivery of high-quality manual compressions may be challenging or dangerous for the provider.”

According to Dr. Allen, “there are times when it’s useful,” such as for a patient with COVID-19, in the cath lab, or in a medical helicopter.
 

Move quickly to defibrillation

“Most of us know that you want to shock as early as possible in shockable rhythms,” Dr. Allen said. Support, she said, comes from a 2008 study that linked delayed defibrillation to lower survival rates. “We want to shock as soon as possible, because your chances of surviving go down for every minute you wait.”

Take special care for patients with confirmed or suspected COVID-19

“Not surprisingly, the goals here are to minimize exposure to staff,” Dr. Allen said.

Put on personal protective equipment before entering the room even if care is delayed, she advised, and reduce the number of staff members in the room below the typical maximum of eight. “In COVID, it should be a maximum of six, and some institutions have even gotten it down to four where the code leaders are outside the room with an iPad.”

Use mechanical compression devices, she advised, and place patients on ventilators as soon as possible. She added: “Use a HEPA [high-efficiency particulate air] filter for all your airway modalities.”

CPR may be challenging in some cases, such as when a large, intubated patient is prone and cannot be quickly or safely flipped over. In those cases, consider posterior chest compressions, also known as reverse CPR, at vertebral positions T7-T10. “We have done reverse CPR on several COVID patients throughout the Emory system,” she said.
 

Debrief right after codes

“You really want to debrief with the code team,” Dr. Allen said. “If you don’t already have a policy in place at your institution, you should help come up with one where you sit down with the team and talk about what could you have done better as a group. It’s not a time to place blame. It’s a time to learn.”

Dr. Allen has disclosed no relevant financial relationships.

This article was updated 7/26/21.

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

Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

“If there’s one universal truth amongst all the patients I’ve interviewed, it’s that they’re often brushed aside, pigeonholed, or, frankly, abandoned,” said Greg Vanichkachorn, MD, MPH, a family physician and founder of Mayo Clinic’s COVID-19 Activity Rehabilitation Program (CARP).

Take a nap. Tough it out. Push through it. Dr. Vanichkachorn describes the frustration voiced by thousands of patients whose lives continue to be disrupted and thrown into upheaval.

Brain fog. Cognitive dysfunction. Headaches. These are just a few of the manifestations of what the National Institutes of Health has termed post-acute sequelae of SARS COVID-2 (PASC), more commonly known as long-COVID.

PASC is loosely defined as symptoms and/or sequelae that persist for several weeks to months after the initial infection has cleared. Data that have accumulated since the COVID-19 outbreak suggest that at least 1 in 3 people who are initially infected may be long-haulers.

A total of 33.6% (95% confidence interval, 11.17-34.07) of patients with COVID-19 experience neurologic sequelae in the first 6 months following resolution of the infection. Almost half of cases (12.8%; 95% CI, 12.36-13.33) represented first-time diagnoses.

“Anecdotally, the longer we go into this, and the more people that, in the past, have been infected with COVID-19, the more patients will be seeing neurologists with some of these complaints,” said Ralph Sacco, MD, professor and Olemberg chair of neurology at University of Miami, and past president of the American Academy of Neurology.
 

Neurologic detritus

Further complicating the epidemiologic picture is the broad array of clinical and functional symptoms. “What we call long-haul COVID is not a single entity,” explained Michel Toledano, MD, a neurology consultant and a member of the CARP team at the Mayo Clinic in Rochester, Minnesota. Patients present with persistent or emergent polysymptomatic and multisystemic diseases that often include neurologic symptoms, he said. In many circumstances, they had an acute infection with either very mild symptoms or no symptoms at all.

“There’s no doubt that these people are experiencing significant neurologic symptoms, but it remains unclear whether the driving factor is mainly systemic or the nervous system independently of what is happening in the body,” he said.

Like patients with SARS-CoV-1 and Middle Eastern respiratory syndrome (MERS), patients recovering from confirmed or suspected SARS-CoV-2 infections experience a variety of self-reported neurologic symptoms that vary in terms of time frame, duration, and severity.

Take Jacqueline Jolly, for example, a 50-year-old single mother and construction permit contractor living outside of Tampa, Florida. She was diagnosed with COVID-19 in January 2021. Jolly explained that she was never sick enough to be admitted to the hospital and yet is still not close to full recovery. Lingering, debilitating symptoms include executive function challenges, anosmia, headaches, and paresthesia that frequently bring her to the edge of losing consciousness. She has not returned to work, despite multiple attempts.

Vicky Nunally, a 35-year-old single mother and medical office assistant who lives in the suburbs of Atlanta, Georgia, recounted that she landed in the intensive care unit with a severe SARS-CoV-2 infection. Roughly 6 months later, she continues to experience debilitating headaches, brain fog, and cognitive delays. Her endometriosis has flared up. She says that she is depressed, anxious, and has returned to therapy. “It makes you feel crazy,” she said.
 

Debilitating, pervasive symptoms

Findings from an international survey of 3,762 respondents that was published on April 21 in medRXiv underscore that PASC occurs predominantly in middle-aged women (78.9% were women; 31% were aged 40-49 years; 25.0% were aged 50-59 years). For the most part, it manifests similarly among people with prior confirmed or suspected SARS-CoV-2 infections. In the study, symptoms were reported in both cohorts well past the initial infection; symptoms persisted past 90 days in 96% of patients and for at least 6 months in 65.2%.

Similarly, a recent study showed that 68% of patients who were enrolled in Mayo Clinic’s CARP as of June 2020 were women, middle aged (mean age, 45 ± 14.2 years), and presented roughly 3 months (94.4 ± 65 days) post diagnosis. Of these patients, 75% had not been previously hospitalized.

In both studies, fatigue and cognitive dysfunction were consistently cited as the most debilitating and pervasive manifestations lasting more than 6 months. Others included postexertional (physical or mental) malaise, sensorimotor symptoms, headaches, and memory problems.

Reports of even more severe neurologic first-time diagnoses are emerging. Findings from the Lancet Psychiatry study showed there was a small but clinically relevant risk for a range of conditions that included intracranial hemorrhage (0.14%; 95% CI, 0.10-0.20), ischemic stroke (0.43%; 95% CI, 0.36-0.52), parkinsonism (0.07%; 95% CI, 0.05-0.12), and nerve root/plexus disorders (2.69%; 95% CI, 2.51-2.89).

Dr. Toledano noted that he’s also seen patients who developed autonomic/small-fiber dysfunction. Preliminary data from a retrospective chart review suggest that the most likely diagnosis is orthostatic intolerance without tachycardia or hypotension.

In the study, 63% (17) of the 27 participants who met the inclusion criteria had abnormal results on function testing, but Composite Autonomic Severity Score results indicated mostly mild disease (sudomotor range, 0-3 [median, 0]; cardiovagal, 0-3 [median, 0]; cardiovascular adrenergic, 0-4 [median, 0]).

“The pattern that’s emerging is consistent with deconditioning,” Dr. Toledano said. “However, a small proportion of patients do have evidence of damage to the nervous system, which is something we’ve seen with other viruses.”
 

Proliferation of long-COVID clinics

A few of these patients with orthostatic intolerance developed postural tachycardia syndrome or experienced exacerbations of preexisting sensory or autonomic small-fiber neuropathies. “These post-viral, autonomic neuropathies tend to be self-limiting, but we’re starting to see different levels of involvement,” Dr. Toledano explained. At present, causality and/or underlying mechanisms are unclear.

Speaking on behalf of the American Academy of Neurology, Dr. Sacco acknowledged the challenges that lie ahead. “Like any neurological symptom that continues to affect a patient’s quality of life, you may need to seek the expertise of a neurologist. The only issue is that some may still not be sure exactly what to do; we don’t have all the data yet,” he said.

On the flip side, he pointed to the lessons of the past year and how quickly health care systems were able to pivot to deal with the pandemic and critically ill patients, then pivot again to disseminate vaccines, and how they are pivoting yet again to address PASC.

Across the nation, numerous hospitals and health care systems and even small private clinics have launched clinics that focus on long-COVID, including Mayo.

The program has a multidisciplinary, collaborative framework and offers both face-to-face and video telemedicine consultations. The latter are geared toward ensuring that under-resourced populations can access needed care and assistance.

“At Mayo, we have a centralized triage system to help target patients’ visits so that appropriate subspecialties and studies can be preordered,” explained Dr. Toledano. During these visits, patients are assessed for underlying conditions and possible signs of decompensation, as well as functional and physical needs and psychosocial challenges. Thereafter, patients enter either CARP, which offers active rehabilitation for up to 3 months after resolution of the acute infection, or the Post-COVID Care Center, which focuses on patients whose condition is not improving or who are demonstrating signs of central sensitization.
 

An uphill battle

Both programs incorporate individually paced occupational and physical therapy aimed at ameliorating symptoms, restoring function, developing psychosocial coping skills, and, ultimately, facilitating a return to work. “The idea is, if we can meet with these patients sooner than later and help them recover in an appropriate fashion, they will exit the program faster,” Dr. Vanichkachorn said. “We do see a group of patients who tend to get better right around the 4-month period.”

Although telemedicine provides an opportunity for clinicians outside these hospital systems to engage patients, Dr. Vanichkachorn pointed out that almost all the initial treatments can be offered in the local community by a provider who has adequate time and knowledge of the condition.

He also acknowledged the potential for an uphill battle, especially among those who cling to the belief that PASC is simply a manifestation of anxiety or depression. “This is something that we’ve seen previously with SARS and MERS, as well as in conjunction with fibromyalgia and chronic fatigue, only now with greater magnitude,” he said. “This is a real condition that has important and huge ramifications on a person’s ability to function.”

The silver lining is that last December, the NIH announced that it was allocating $1.1 billion for research through its NIH PASC Initiative. Like other institutions, Mayo is waiting to hear what it has been awarded. In the meantime, it has developed a biorepository of patient samples to better understand pathophysiologic mechanisms underlying PASC and to identify possible biomarkers that differentiate these patients.

Despite the challenges, Dr. Vanichkachorn is hopeful. “If we can get a concrete understanding of what is occurring on the chemical level and develop diagnostic tests, then the education will follow. Providers won’t be able to ignore it any longer,” he said.

The interviewees have disclosed no relevant financial relationships.

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

“If there’s one universal truth amongst all the patients I’ve interviewed, it’s that they’re often brushed aside, pigeonholed, or, frankly, abandoned,” said Greg Vanichkachorn, MD, MPH, a family physician and founder of Mayo Clinic’s COVID-19 Activity Rehabilitation Program (CARP).

Take a nap. Tough it out. Push through it. Dr. Vanichkachorn describes the frustration voiced by thousands of patients whose lives continue to be disrupted and thrown into upheaval.

Brain fog. Cognitive dysfunction. Headaches. These are just a few of the manifestations of what the National Institutes of Health has termed post-acute sequelae of SARS COVID-2 (PASC), more commonly known as long-COVID.

PASC is loosely defined as symptoms and/or sequelae that persist for several weeks to months after the initial infection has cleared. Data that have accumulated since the COVID-19 outbreak suggest that at least 1 in 3 people who are initially infected may be long-haulers.

A total of 33.6% (95% confidence interval, 11.17-34.07) of patients with COVID-19 experience neurologic sequelae in the first 6 months following resolution of the infection. Almost half of cases (12.8%; 95% CI, 12.36-13.33) represented first-time diagnoses.

“Anecdotally, the longer we go into this, and the more people that, in the past, have been infected with COVID-19, the more patients will be seeing neurologists with some of these complaints,” said Ralph Sacco, MD, professor and Olemberg chair of neurology at University of Miami, and past president of the American Academy of Neurology.
 

Neurologic detritus

Further complicating the epidemiologic picture is the broad array of clinical and functional symptoms. “What we call long-haul COVID is not a single entity,” explained Michel Toledano, MD, a neurology consultant and a member of the CARP team at the Mayo Clinic in Rochester, Minnesota. Patients present with persistent or emergent polysymptomatic and multisystemic diseases that often include neurologic symptoms, he said. In many circumstances, they had an acute infection with either very mild symptoms or no symptoms at all.

“There’s no doubt that these people are experiencing significant neurologic symptoms, but it remains unclear whether the driving factor is mainly systemic or the nervous system independently of what is happening in the body,” he said.

Like patients with SARS-CoV-1 and Middle Eastern respiratory syndrome (MERS), patients recovering from confirmed or suspected SARS-CoV-2 infections experience a variety of self-reported neurologic symptoms that vary in terms of time frame, duration, and severity.

Take Jacqueline Jolly, for example, a 50-year-old single mother and construction permit contractor living outside of Tampa, Florida. She was diagnosed with COVID-19 in January 2021. Jolly explained that she was never sick enough to be admitted to the hospital and yet is still not close to full recovery. Lingering, debilitating symptoms include executive function challenges, anosmia, headaches, and paresthesia that frequently bring her to the edge of losing consciousness. She has not returned to work, despite multiple attempts.

Vicky Nunally, a 35-year-old single mother and medical office assistant who lives in the suburbs of Atlanta, Georgia, recounted that she landed in the intensive care unit with a severe SARS-CoV-2 infection. Roughly 6 months later, she continues to experience debilitating headaches, brain fog, and cognitive delays. Her endometriosis has flared up. She says that she is depressed, anxious, and has returned to therapy. “It makes you feel crazy,” she said.
 

Debilitating, pervasive symptoms

Findings from an international survey of 3,762 respondents that was published on April 21 in medRXiv underscore that PASC occurs predominantly in middle-aged women (78.9% were women; 31% were aged 40-49 years; 25.0% were aged 50-59 years). For the most part, it manifests similarly among people with prior confirmed or suspected SARS-CoV-2 infections. In the study, symptoms were reported in both cohorts well past the initial infection; symptoms persisted past 90 days in 96% of patients and for at least 6 months in 65.2%.

Similarly, a recent study showed that 68% of patients who were enrolled in Mayo Clinic’s CARP as of June 2020 were women, middle aged (mean age, 45 ± 14.2 years), and presented roughly 3 months (94.4 ± 65 days) post diagnosis. Of these patients, 75% had not been previously hospitalized.

In both studies, fatigue and cognitive dysfunction were consistently cited as the most debilitating and pervasive manifestations lasting more than 6 months. Others included postexertional (physical or mental) malaise, sensorimotor symptoms, headaches, and memory problems.

Reports of even more severe neurologic first-time diagnoses are emerging. Findings from the Lancet Psychiatry study showed there was a small but clinically relevant risk for a range of conditions that included intracranial hemorrhage (0.14%; 95% CI, 0.10-0.20), ischemic stroke (0.43%; 95% CI, 0.36-0.52), parkinsonism (0.07%; 95% CI, 0.05-0.12), and nerve root/plexus disorders (2.69%; 95% CI, 2.51-2.89).

Dr. Toledano noted that he’s also seen patients who developed autonomic/small-fiber dysfunction. Preliminary data from a retrospective chart review suggest that the most likely diagnosis is orthostatic intolerance without tachycardia or hypotension.

In the study, 63% (17) of the 27 participants who met the inclusion criteria had abnormal results on function testing, but Composite Autonomic Severity Score results indicated mostly mild disease (sudomotor range, 0-3 [median, 0]; cardiovagal, 0-3 [median, 0]; cardiovascular adrenergic, 0-4 [median, 0]).

“The pattern that’s emerging is consistent with deconditioning,” Dr. Toledano said. “However, a small proportion of patients do have evidence of damage to the nervous system, which is something we’ve seen with other viruses.”
 

Proliferation of long-COVID clinics

A few of these patients with orthostatic intolerance developed postural tachycardia syndrome or experienced exacerbations of preexisting sensory or autonomic small-fiber neuropathies. “These post-viral, autonomic neuropathies tend to be self-limiting, but we’re starting to see different levels of involvement,” Dr. Toledano explained. At present, causality and/or underlying mechanisms are unclear.

Speaking on behalf of the American Academy of Neurology, Dr. Sacco acknowledged the challenges that lie ahead. “Like any neurological symptom that continues to affect a patient’s quality of life, you may need to seek the expertise of a neurologist. The only issue is that some may still not be sure exactly what to do; we don’t have all the data yet,” he said.

On the flip side, he pointed to the lessons of the past year and how quickly health care systems were able to pivot to deal with the pandemic and critically ill patients, then pivot again to disseminate vaccines, and how they are pivoting yet again to address PASC.

Across the nation, numerous hospitals and health care systems and even small private clinics have launched clinics that focus on long-COVID, including Mayo.

The program has a multidisciplinary, collaborative framework and offers both face-to-face and video telemedicine consultations. The latter are geared toward ensuring that under-resourced populations can access needed care and assistance.

“At Mayo, we have a centralized triage system to help target patients’ visits so that appropriate subspecialties and studies can be preordered,” explained Dr. Toledano. During these visits, patients are assessed for underlying conditions and possible signs of decompensation, as well as functional and physical needs and psychosocial challenges. Thereafter, patients enter either CARP, which offers active rehabilitation for up to 3 months after resolution of the acute infection, or the Post-COVID Care Center, which focuses on patients whose condition is not improving or who are demonstrating signs of central sensitization.
 

An uphill battle

Both programs incorporate individually paced occupational and physical therapy aimed at ameliorating symptoms, restoring function, developing psychosocial coping skills, and, ultimately, facilitating a return to work. “The idea is, if we can meet with these patients sooner than later and help them recover in an appropriate fashion, they will exit the program faster,” Dr. Vanichkachorn said. “We do see a group of patients who tend to get better right around the 4-month period.”

Although telemedicine provides an opportunity for clinicians outside these hospital systems to engage patients, Dr. Vanichkachorn pointed out that almost all the initial treatments can be offered in the local community by a provider who has adequate time and knowledge of the condition.

He also acknowledged the potential for an uphill battle, especially among those who cling to the belief that PASC is simply a manifestation of anxiety or depression. “This is something that we’ve seen previously with SARS and MERS, as well as in conjunction with fibromyalgia and chronic fatigue, only now with greater magnitude,” he said. “This is a real condition that has important and huge ramifications on a person’s ability to function.”

The silver lining is that last December, the NIH announced that it was allocating $1.1 billion for research through its NIH PASC Initiative. Like other institutions, Mayo is waiting to hear what it has been awarded. In the meantime, it has developed a biorepository of patient samples to better understand pathophysiologic mechanisms underlying PASC and to identify possible biomarkers that differentiate these patients.

Despite the challenges, Dr. Vanichkachorn is hopeful. “If we can get a concrete understanding of what is occurring on the chemical level and develop diagnostic tests, then the education will follow. Providers won’t be able to ignore it any longer,” he said.

The interviewees have disclosed no relevant financial relationships.

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

“If there’s one universal truth amongst all the patients I’ve interviewed, it’s that they’re often brushed aside, pigeonholed, or, frankly, abandoned,” said Greg Vanichkachorn, MD, MPH, a family physician and founder of Mayo Clinic’s COVID-19 Activity Rehabilitation Program (CARP).

Take a nap. Tough it out. Push through it. Dr. Vanichkachorn describes the frustration voiced by thousands of patients whose lives continue to be disrupted and thrown into upheaval.

Brain fog. Cognitive dysfunction. Headaches. These are just a few of the manifestations of what the National Institutes of Health has termed post-acute sequelae of SARS COVID-2 (PASC), more commonly known as long-COVID.

PASC is loosely defined as symptoms and/or sequelae that persist for several weeks to months after the initial infection has cleared. Data that have accumulated since the COVID-19 outbreak suggest that at least 1 in 3 people who are initially infected may be long-haulers.

A total of 33.6% (95% confidence interval, 11.17-34.07) of patients with COVID-19 experience neurologic sequelae in the first 6 months following resolution of the infection. Almost half of cases (12.8%; 95% CI, 12.36-13.33) represented first-time diagnoses.

“Anecdotally, the longer we go into this, and the more people that, in the past, have been infected with COVID-19, the more patients will be seeing neurologists with some of these complaints,” said Ralph Sacco, MD, professor and Olemberg chair of neurology at University of Miami, and past president of the American Academy of Neurology.
 

Neurologic detritus

Further complicating the epidemiologic picture is the broad array of clinical and functional symptoms. “What we call long-haul COVID is not a single entity,” explained Michel Toledano, MD, a neurology consultant and a member of the CARP team at the Mayo Clinic in Rochester, Minnesota. Patients present with persistent or emergent polysymptomatic and multisystemic diseases that often include neurologic symptoms, he said. In many circumstances, they had an acute infection with either very mild symptoms or no symptoms at all.

“There’s no doubt that these people are experiencing significant neurologic symptoms, but it remains unclear whether the driving factor is mainly systemic or the nervous system independently of what is happening in the body,” he said.

Like patients with SARS-CoV-1 and Middle Eastern respiratory syndrome (MERS), patients recovering from confirmed or suspected SARS-CoV-2 infections experience a variety of self-reported neurologic symptoms that vary in terms of time frame, duration, and severity.

Take Jacqueline Jolly, for example, a 50-year-old single mother and construction permit contractor living outside of Tampa, Florida. She was diagnosed with COVID-19 in January 2021. Jolly explained that she was never sick enough to be admitted to the hospital and yet is still not close to full recovery. Lingering, debilitating symptoms include executive function challenges, anosmia, headaches, and paresthesia that frequently bring her to the edge of losing consciousness. She has not returned to work, despite multiple attempts.

Vicky Nunally, a 35-year-old single mother and medical office assistant who lives in the suburbs of Atlanta, Georgia, recounted that she landed in the intensive care unit with a severe SARS-CoV-2 infection. Roughly 6 months later, she continues to experience debilitating headaches, brain fog, and cognitive delays. Her endometriosis has flared up. She says that she is depressed, anxious, and has returned to therapy. “It makes you feel crazy,” she said.
 

Debilitating, pervasive symptoms

Findings from an international survey of 3,762 respondents that was published on April 21 in medRXiv underscore that PASC occurs predominantly in middle-aged women (78.9% were women; 31% were aged 40-49 years; 25.0% were aged 50-59 years). For the most part, it manifests similarly among people with prior confirmed or suspected SARS-CoV-2 infections. In the study, symptoms were reported in both cohorts well past the initial infection; symptoms persisted past 90 days in 96% of patients and for at least 6 months in 65.2%.

Similarly, a recent study showed that 68% of patients who were enrolled in Mayo Clinic’s CARP as of June 2020 were women, middle aged (mean age, 45 ± 14.2 years), and presented roughly 3 months (94.4 ± 65 days) post diagnosis. Of these patients, 75% had not been previously hospitalized.

In both studies, fatigue and cognitive dysfunction were consistently cited as the most debilitating and pervasive manifestations lasting more than 6 months. Others included postexertional (physical or mental) malaise, sensorimotor symptoms, headaches, and memory problems.

Reports of even more severe neurologic first-time diagnoses are emerging. Findings from the Lancet Psychiatry study showed there was a small but clinically relevant risk for a range of conditions that included intracranial hemorrhage (0.14%; 95% CI, 0.10-0.20), ischemic stroke (0.43%; 95% CI, 0.36-0.52), parkinsonism (0.07%; 95% CI, 0.05-0.12), and nerve root/plexus disorders (2.69%; 95% CI, 2.51-2.89).

Dr. Toledano noted that he’s also seen patients who developed autonomic/small-fiber dysfunction. Preliminary data from a retrospective chart review suggest that the most likely diagnosis is orthostatic intolerance without tachycardia or hypotension.

In the study, 63% (17) of the 27 participants who met the inclusion criteria had abnormal results on function testing, but Composite Autonomic Severity Score results indicated mostly mild disease (sudomotor range, 0-3 [median, 0]; cardiovagal, 0-3 [median, 0]; cardiovascular adrenergic, 0-4 [median, 0]).

“The pattern that’s emerging is consistent with deconditioning,” Dr. Toledano said. “However, a small proportion of patients do have evidence of damage to the nervous system, which is something we’ve seen with other viruses.”
 

Proliferation of long-COVID clinics

A few of these patients with orthostatic intolerance developed postural tachycardia syndrome or experienced exacerbations of preexisting sensory or autonomic small-fiber neuropathies. “These post-viral, autonomic neuropathies tend to be self-limiting, but we’re starting to see different levels of involvement,” Dr. Toledano explained. At present, causality and/or underlying mechanisms are unclear.

Speaking on behalf of the American Academy of Neurology, Dr. Sacco acknowledged the challenges that lie ahead. “Like any neurological symptom that continues to affect a patient’s quality of life, you may need to seek the expertise of a neurologist. The only issue is that some may still not be sure exactly what to do; we don’t have all the data yet,” he said.

On the flip side, he pointed to the lessons of the past year and how quickly health care systems were able to pivot to deal with the pandemic and critically ill patients, then pivot again to disseminate vaccines, and how they are pivoting yet again to address PASC.

Across the nation, numerous hospitals and health care systems and even small private clinics have launched clinics that focus on long-COVID, including Mayo.

The program has a multidisciplinary, collaborative framework and offers both face-to-face and video telemedicine consultations. The latter are geared toward ensuring that under-resourced populations can access needed care and assistance.

“At Mayo, we have a centralized triage system to help target patients’ visits so that appropriate subspecialties and studies can be preordered,” explained Dr. Toledano. During these visits, patients are assessed for underlying conditions and possible signs of decompensation, as well as functional and physical needs and psychosocial challenges. Thereafter, patients enter either CARP, which offers active rehabilitation for up to 3 months after resolution of the acute infection, or the Post-COVID Care Center, which focuses on patients whose condition is not improving or who are demonstrating signs of central sensitization.
 

An uphill battle

Both programs incorporate individually paced occupational and physical therapy aimed at ameliorating symptoms, restoring function, developing psychosocial coping skills, and, ultimately, facilitating a return to work. “The idea is, if we can meet with these patients sooner than later and help them recover in an appropriate fashion, they will exit the program faster,” Dr. Vanichkachorn said. “We do see a group of patients who tend to get better right around the 4-month period.”

Although telemedicine provides an opportunity for clinicians outside these hospital systems to engage patients, Dr. Vanichkachorn pointed out that almost all the initial treatments can be offered in the local community by a provider who has adequate time and knowledge of the condition.

He also acknowledged the potential for an uphill battle, especially among those who cling to the belief that PASC is simply a manifestation of anxiety or depression. “This is something that we’ve seen previously with SARS and MERS, as well as in conjunction with fibromyalgia and chronic fatigue, only now with greater magnitude,” he said. “This is a real condition that has important and huge ramifications on a person’s ability to function.”

The silver lining is that last December, the NIH announced that it was allocating $1.1 billion for research through its NIH PASC Initiative. Like other institutions, Mayo is waiting to hear what it has been awarded. In the meantime, it has developed a biorepository of patient samples to better understand pathophysiologic mechanisms underlying PASC and to identify possible biomarkers that differentiate these patients.

Despite the challenges, Dr. Vanichkachorn is hopeful. “If we can get a concrete understanding of what is occurring on the chemical level and develop diagnostic tests, then the education will follow. Providers won’t be able to ignore it any longer,” he said.

The interviewees have disclosed no relevant financial relationships.

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