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ACP addresses ethical issues for ‘grateful patients’ physician fundraising
Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.
“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.
Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.
In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.
“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.
Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.
Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor.
Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.
“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”
Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.
“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.
A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.
“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.
Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.
“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.
An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.
A version of this article first appeared on Medscape.com.
Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.
“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.
Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.
In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.
“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.
Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.
Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor.
Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.
“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”
Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.
“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.
A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.
“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.
Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.
“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.
An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.
A version of this article first appeared on Medscape.com.
Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.
“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.
Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.
In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.
“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.
Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.
Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor.
Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.
“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”
Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.
“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.
A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.
“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.
Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.
“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.
An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Commentary: DMARD types, guselkumab, and interleukin inhibitors in PsA, October 2023
To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.
Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA, > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.
Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.
Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.
To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.
Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA, > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.
Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.
Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.
To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.
Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA, > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.
Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.
Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.
Overburdened: Health care workers more likely to die by suicide
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study.
If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.
It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.
I’m speaking in generalities, of course.
I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.
Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.
And, according to this paper in JAMA, it is those people who may be suffering most of all.
The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.
Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.
Let’s take a look at the numbers.
I’m showing you age- and sex-standardized rates of death from suicide, starting with non–health care workers. In this study, physicians have similar rates of death from suicide to the general population. Nurses have higher rates, but health care support workers – nurses’ aides, home health aides – have rates nearly twice that of the general population.
Only social and behavioral health workers had rates lower than those in the general population, perhaps because they know how to access life-saving resources.
Of course, these groups differ in a lot of ways – education and income, for example. But even after adjustment for these factors as well as for sex, race, and marital status, the results persist. The only group with even a trend toward lower suicide rates are social and behavioral health workers.
There has been much hand-wringing about rates of physician suicide in the past. It is still a very real problem. But this paper finally highlights that there is a lot more to the health care profession than physicians. It’s time we acknowledge and support the people in our profession who seem to be suffering more than any of us: the aides, the techs, the support staff – the overworked and underpaid who have to deal with all the stresses that physicians like me face and then some.
There’s more to suicide risk than just your job; I know that. Family matters. Relationships matter. Medical and psychiatric illnesses matter. But to ignore this problem when it is right here, in our own house so to speak, can’t continue.
Might I suggest we start by asking someone in our profession – whether doctor, nurse, aide, or tech – how they are doing. How they are really doing. And when we are done listening, we use what we hear to advocate for real change.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study.
If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.
It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.
I’m speaking in generalities, of course.
I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.
Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.
And, according to this paper in JAMA, it is those people who may be suffering most of all.
The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.
Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.
Let’s take a look at the numbers.
I’m showing you age- and sex-standardized rates of death from suicide, starting with non–health care workers. In this study, physicians have similar rates of death from suicide to the general population. Nurses have higher rates, but health care support workers – nurses’ aides, home health aides – have rates nearly twice that of the general population.
Only social and behavioral health workers had rates lower than those in the general population, perhaps because they know how to access life-saving resources.
Of course, these groups differ in a lot of ways – education and income, for example. But even after adjustment for these factors as well as for sex, race, and marital status, the results persist. The only group with even a trend toward lower suicide rates are social and behavioral health workers.
There has been much hand-wringing about rates of physician suicide in the past. It is still a very real problem. But this paper finally highlights that there is a lot more to the health care profession than physicians. It’s time we acknowledge and support the people in our profession who seem to be suffering more than any of us: the aides, the techs, the support staff – the overworked and underpaid who have to deal with all the stresses that physicians like me face and then some.
There’s more to suicide risk than just your job; I know that. Family matters. Relationships matter. Medical and psychiatric illnesses matter. But to ignore this problem when it is right here, in our own house so to speak, can’t continue.
Might I suggest we start by asking someone in our profession – whether doctor, nurse, aide, or tech – how they are doing. How they are really doing. And when we are done listening, we use what we hear to advocate for real change.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study.
If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.
It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.
I’m speaking in generalities, of course.
I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.
Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.
And, according to this paper in JAMA, it is those people who may be suffering most of all.
The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.
Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.
Let’s take a look at the numbers.
I’m showing you age- and sex-standardized rates of death from suicide, starting with non–health care workers. In this study, physicians have similar rates of death from suicide to the general population. Nurses have higher rates, but health care support workers – nurses’ aides, home health aides – have rates nearly twice that of the general population.
Only social and behavioral health workers had rates lower than those in the general population, perhaps because they know how to access life-saving resources.
Of course, these groups differ in a lot of ways – education and income, for example. But even after adjustment for these factors as well as for sex, race, and marital status, the results persist. The only group with even a trend toward lower suicide rates are social and behavioral health workers.
There has been much hand-wringing about rates of physician suicide in the past. It is still a very real problem. But this paper finally highlights that there is a lot more to the health care profession than physicians. It’s time we acknowledge and support the people in our profession who seem to be suffering more than any of us: the aides, the techs, the support staff – the overworked and underpaid who have to deal with all the stresses that physicians like me face and then some.
There’s more to suicide risk than just your job; I know that. Family matters. Relationships matter. Medical and psychiatric illnesses matter. But to ignore this problem when it is right here, in our own house so to speak, can’t continue.
Might I suggest we start by asking someone in our profession – whether doctor, nurse, aide, or tech – how they are doing. How they are really doing. And when we are done listening, we use what we hear to advocate for real change.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
How to get paid if your patient passes on
The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns,
“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”
Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.
“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”
The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.
In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
Hoping the doctor’s office writes it off
“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”
Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.
Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.
At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.
“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”
The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.
“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
Insurance coverage
Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.
Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.
“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”
In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.
Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)
The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.
Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
How to minimize losses
In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.
There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.
To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.
While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.
“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”
When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.
“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.
It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.
Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.
“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”
A version of this article first appeared on Medscape.com.
The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns,
“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”
Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.
“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”
The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.
In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
Hoping the doctor’s office writes it off
“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”
Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.
Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.
At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.
“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”
The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.
“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
Insurance coverage
Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.
Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.
“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”
In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.
Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)
The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.
Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
How to minimize losses
In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.
There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.
To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.
While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.
“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”
When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.
“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.
It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.
Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.
“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”
A version of this article first appeared on Medscape.com.
The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns,
“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”
Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.
“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”
The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.
In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
Hoping the doctor’s office writes it off
“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”
Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.
Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.
At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.
“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”
The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.
“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
Insurance coverage
Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.
Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.
“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”
In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.
Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)
The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.
Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
How to minimize losses
In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.
There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.
To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.
While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.
“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”
When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.
“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.
It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.
Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.
“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”
A version of this article first appeared on Medscape.com.
People with long COVID have specific blood biomarkers, study says
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
Are vitamin D levels key to canagliflozin’s fracture risk?
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.
The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.
“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.
In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.
When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).
“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.
Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).
Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.
Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).
“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.
The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”
The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Patients with rheumatism have premature immune system aging
LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.
“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”
“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.
While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
‘Inflamm-aging’
“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.
As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.
The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.
With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.
This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
‘Bad old T cells’
Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”
In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
Power sources fail
In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”
At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.
T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”
Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
Inflammatory cell death
In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”
In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.
Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”
Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.
When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”
This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.
LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.
“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”
“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.
While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
‘Inflamm-aging’
“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.
As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.
The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.
With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.
This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
‘Bad old T cells’
Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”
In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
Power sources fail
In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”
At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.
T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”
Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
Inflammatory cell death
In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”
In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.
Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”
Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.
When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”
This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.
LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.
“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”
“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.
While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
‘Inflamm-aging’
“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.
As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.
The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.
With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.
This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
‘Bad old T cells’
Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”
In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
Power sources fail
In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”
At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.
T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”
Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
Inflammatory cell death
In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”
In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.
Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”
Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.
When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”
This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.
Ginger consumption may mitigate neutrophil dysfunction and inflammation
TOPLINE:
Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.
METHODOLOGY:
- Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
- Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
- The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.
TAKEAWAY:
- Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
- Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
- The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
- Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.
IN PRACTICE:
The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.
SOURCE:
First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.
LIMITATIONS:
More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.
DISCLOSURES:
The study received no outside funding. The researchers report no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.
METHODOLOGY:
- Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
- Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
- The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.
TAKEAWAY:
- Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
- Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
- The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
- Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.
IN PRACTICE:
The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.
SOURCE:
First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.
LIMITATIONS:
More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.
DISCLOSURES:
The study received no outside funding. The researchers report no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.
METHODOLOGY:
- Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
- Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
- The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.
TAKEAWAY:
- Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
- Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
- The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
- Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.
IN PRACTICE:
The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.
SOURCE:
First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.
LIMITATIONS:
More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.
DISCLOSURES:
The study received no outside funding. The researchers report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Mortality in ankylosing spondylitis: CV disease, drug abuse are big contributors
TOPLINE:
Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.
METHODOLOGY:
- Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
- The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
- The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.
TAKEAWAY:
- Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
- The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
- Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
- Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.
IN PRACTICE:
Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.
SOURCE:
First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).
LIMITATIONS:
The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.
DISCLOSURES:
The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.
A version of this article first appeared on Medscape.com.
TOPLINE:
Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.
METHODOLOGY:
- Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
- The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
- The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.
TAKEAWAY:
- Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
- The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
- Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
- Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.
IN PRACTICE:
Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.
SOURCE:
First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).
LIMITATIONS:
The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.
DISCLOSURES:
The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.
A version of this article first appeared on Medscape.com.
TOPLINE:
Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.
METHODOLOGY:
- Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
- The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
- The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.
TAKEAWAY:
- Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
- The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
- Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
- Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.
IN PRACTICE:
Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.
SOURCE:
First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).
LIMITATIONS:
The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.
DISCLOSURES:
The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.
A version of this article first appeared on Medscape.com.
Progressive pulmonary fibrosis: treatment and support
MILAN – Numerous unresolved questions surround progressive pulmonary fibrosis (PPF) treatment, according to Elisabeth Bendstrup, MD, PhD, a researcher and clinical professor in the department of clinical medicine – department of respiratory diseases and allergy, Aarhus (Denmark) University, Denmark. These questions regard the optimal timing for treatment initiation, the role of available medications, either as monotherapy or in combination, and nonpharmacologic support options.
What’s in the toolbox?
Pulmonologists who manage PPF have a range of treatment options at their disposal. This includes careful patient observation, with treatment initiation based on clinical necessity. The therapeutic arsenal comprises immunomodulatory treatments, antifibrotic agents, palliative and supportive care, and, for a minority of patients, lung transplantation.
“Once a patient is diagnosed with PPF, it is important to remember that the diagnostic criteria from the guidelines are not exactly the same of those accepted for the reimbursement of antifibrotic treatments in different countries,” Dr. Bendstrup said, suggesting that nonclinical considerations could also potentially influence the treatment choice. She spoke at the annual congress of the European Respiratory Society.
Michael Kreuter, MD, director of the Lung Center at the University Hospital in Mainz, Germany, provided insight into the introduction of antifibrotic drugs for the treatment of PPF. Drawing from nearly a decade ago when the first antifibrotic medication was approved for idiopathic pulmonary fibrosis (IPF), Dr. Kreuter noted its effectiveness in slowing disease progression, although it does not reverse it. Subsequently, the discovery that non-IPF diseases, such as rheumatoid arthritis, exhibited IPF-like behavior led to the exploration of the use of the same drugs for similar conditions, even if not IPF.
“That’s how antifibrotic treatments came into place. Now we have more trials and data to be discussed in the future,” Dr. Kreuter added. He highlighted that antifibrotic drugs are effective for several diseases. Most of those diseases are treated with different anti-inflammatory drugs, which makes it difficult to decide when to start antifibrotic therapy and how to eventually combine it with different pharmacologic approaches.
A pivotal starting point
a question only partially addressed by existing guidelines. Dr. Bendstrup advocated for a comprehensive baseline evaluation. Factors to be considered include symptom burden, the severity of lung decline, radiologic characteristics, signs of alveolar inflammation, progression risk factors, quality of life, patient preferences, and medical history. “All these should be best discussed in a multidisciplinary team, including pulmonologists, nurses, experts in palliative care, occupational physicians, and more,” she said.
Current guidelines recommend nintedanib for PPF treatment for patients who have failed standard management for fibrotic interstitial lung disease (ILD) other than IPF. However, the definition of “standard management” remains a topic of debate, and it is acknowledged that evidence-based guidance for a standard of care varies among patients. Dr. Bendstrup pointed out the limited guidance clinicians receive from these guidelines. “As clinicians, we are not left with very much help from here.”
Choosing the right approach
Dr. Bendstrup delved into the factors influencing the choice between antifibrotic and anti-inflammatory therapies. This decision hinges on whether the patient presents with a predominantly inflammatory or a fibrotic progressive phenotype. Certain clinical characteristics contribute to the decision. Factors such as younger age, female gender, and the presence of connective tissue disease lean toward an inflammatory phenotype. Radiologic patterns, such as organized pneumonia, hypersensitivity pneumonia, or usual interstitial pneumonia–like patterns also provide valuable clues. Additionally, genetics plays a role, with shorter telomeres indicating a more fibrotic phenotype and an increased risk of immunomodulatory treatment side effects in non-IPF ILDs.
Bendstrup referred to a recent position paper on treatment recommendations and many other studies that support the use of different treatments for patients with PPF. The authors highlighted limited evidence for immunomodulation in fibrotic ILD, though such treatment is generally used except for ILD associated with systemic sclerosis. Moreover, the guidelines conditionally recommend nintedanib and call for further research on pirfenidone in PPF.
“We need intelligent, well-designed trials looking at subgroups of patients at higher risk, maybe based on molecular identification. We also need to have good biomarkers to better classify our patients based on disease behavior and treatment response. There’s a lot of discussion of biomarkers for progression, much less – if any – on biomarkers for the response to treatment. And we need them as well,” Dr. Bendstrup said in an interview.
The role of supportive care
Effective PPF treatment extends beyond pharmacologic interventions. It encompasses symptom management, patient education on vaccination and smoking cessation, and fostering social support networks. Psychological support, supplemental oxygen therapy, and pulmonary rehabilitation are integral components of care.
Elisabeth Robertson, a PPF patient representative from the United Kingdom, emphasized the importance of palliative care, not just in end-of-life scenarios but throughout the patient’s journey. Palliative care encompasses symptom alleviation, enabling patients to stay at home when possible, addressing mental health, and preparing for the end of life. Such holistic care can significantly enhance the patient’s quality of life.
The cochair of the session, Marlies S. Wijsenbeek, MD, PhD, pulmonary physician and head of the ILD Centre at the Erasmus University Medical Centre, Rotterdam, the Netherlands, underscored that palliative care begins at diagnosis and involves managing symptom burdens. “Supportive care also includes nurses, as they are precious for the patients while answering their questions and can help save time for the doctors,” she said in an interview.
In the discussion on treatment decisions, experts agreed on the pivotal role of patients in decision-making. However, Dr. Kreuter highlighted two critical factors that influence successful patient-doctor interactions: the cultural backgrounds of patients and their relatives, and the attitudes of health care providers.
Dr. Bendstrup has received honoraria or consultation fees from Boehringer Ingelheim, Roche, Astra Zeneca, Chiesi, and Daiichi Sankyo. Ms. Robertson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – Numerous unresolved questions surround progressive pulmonary fibrosis (PPF) treatment, according to Elisabeth Bendstrup, MD, PhD, a researcher and clinical professor in the department of clinical medicine – department of respiratory diseases and allergy, Aarhus (Denmark) University, Denmark. These questions regard the optimal timing for treatment initiation, the role of available medications, either as monotherapy or in combination, and nonpharmacologic support options.
What’s in the toolbox?
Pulmonologists who manage PPF have a range of treatment options at their disposal. This includes careful patient observation, with treatment initiation based on clinical necessity. The therapeutic arsenal comprises immunomodulatory treatments, antifibrotic agents, palliative and supportive care, and, for a minority of patients, lung transplantation.
“Once a patient is diagnosed with PPF, it is important to remember that the diagnostic criteria from the guidelines are not exactly the same of those accepted for the reimbursement of antifibrotic treatments in different countries,” Dr. Bendstrup said, suggesting that nonclinical considerations could also potentially influence the treatment choice. She spoke at the annual congress of the European Respiratory Society.
Michael Kreuter, MD, director of the Lung Center at the University Hospital in Mainz, Germany, provided insight into the introduction of antifibrotic drugs for the treatment of PPF. Drawing from nearly a decade ago when the first antifibrotic medication was approved for idiopathic pulmonary fibrosis (IPF), Dr. Kreuter noted its effectiveness in slowing disease progression, although it does not reverse it. Subsequently, the discovery that non-IPF diseases, such as rheumatoid arthritis, exhibited IPF-like behavior led to the exploration of the use of the same drugs for similar conditions, even if not IPF.
“That’s how antifibrotic treatments came into place. Now we have more trials and data to be discussed in the future,” Dr. Kreuter added. He highlighted that antifibrotic drugs are effective for several diseases. Most of those diseases are treated with different anti-inflammatory drugs, which makes it difficult to decide when to start antifibrotic therapy and how to eventually combine it with different pharmacologic approaches.
A pivotal starting point
a question only partially addressed by existing guidelines. Dr. Bendstrup advocated for a comprehensive baseline evaluation. Factors to be considered include symptom burden, the severity of lung decline, radiologic characteristics, signs of alveolar inflammation, progression risk factors, quality of life, patient preferences, and medical history. “All these should be best discussed in a multidisciplinary team, including pulmonologists, nurses, experts in palliative care, occupational physicians, and more,” she said.
Current guidelines recommend nintedanib for PPF treatment for patients who have failed standard management for fibrotic interstitial lung disease (ILD) other than IPF. However, the definition of “standard management” remains a topic of debate, and it is acknowledged that evidence-based guidance for a standard of care varies among patients. Dr. Bendstrup pointed out the limited guidance clinicians receive from these guidelines. “As clinicians, we are not left with very much help from here.”
Choosing the right approach
Dr. Bendstrup delved into the factors influencing the choice between antifibrotic and anti-inflammatory therapies. This decision hinges on whether the patient presents with a predominantly inflammatory or a fibrotic progressive phenotype. Certain clinical characteristics contribute to the decision. Factors such as younger age, female gender, and the presence of connective tissue disease lean toward an inflammatory phenotype. Radiologic patterns, such as organized pneumonia, hypersensitivity pneumonia, or usual interstitial pneumonia–like patterns also provide valuable clues. Additionally, genetics plays a role, with shorter telomeres indicating a more fibrotic phenotype and an increased risk of immunomodulatory treatment side effects in non-IPF ILDs.
Bendstrup referred to a recent position paper on treatment recommendations and many other studies that support the use of different treatments for patients with PPF. The authors highlighted limited evidence for immunomodulation in fibrotic ILD, though such treatment is generally used except for ILD associated with systemic sclerosis. Moreover, the guidelines conditionally recommend nintedanib and call for further research on pirfenidone in PPF.
“We need intelligent, well-designed trials looking at subgroups of patients at higher risk, maybe based on molecular identification. We also need to have good biomarkers to better classify our patients based on disease behavior and treatment response. There’s a lot of discussion of biomarkers for progression, much less – if any – on biomarkers for the response to treatment. And we need them as well,” Dr. Bendstrup said in an interview.
The role of supportive care
Effective PPF treatment extends beyond pharmacologic interventions. It encompasses symptom management, patient education on vaccination and smoking cessation, and fostering social support networks. Psychological support, supplemental oxygen therapy, and pulmonary rehabilitation are integral components of care.
Elisabeth Robertson, a PPF patient representative from the United Kingdom, emphasized the importance of palliative care, not just in end-of-life scenarios but throughout the patient’s journey. Palliative care encompasses symptom alleviation, enabling patients to stay at home when possible, addressing mental health, and preparing for the end of life. Such holistic care can significantly enhance the patient’s quality of life.
The cochair of the session, Marlies S. Wijsenbeek, MD, PhD, pulmonary physician and head of the ILD Centre at the Erasmus University Medical Centre, Rotterdam, the Netherlands, underscored that palliative care begins at diagnosis and involves managing symptom burdens. “Supportive care also includes nurses, as they are precious for the patients while answering their questions and can help save time for the doctors,” she said in an interview.
In the discussion on treatment decisions, experts agreed on the pivotal role of patients in decision-making. However, Dr. Kreuter highlighted two critical factors that influence successful patient-doctor interactions: the cultural backgrounds of patients and their relatives, and the attitudes of health care providers.
Dr. Bendstrup has received honoraria or consultation fees from Boehringer Ingelheim, Roche, Astra Zeneca, Chiesi, and Daiichi Sankyo. Ms. Robertson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – Numerous unresolved questions surround progressive pulmonary fibrosis (PPF) treatment, according to Elisabeth Bendstrup, MD, PhD, a researcher and clinical professor in the department of clinical medicine – department of respiratory diseases and allergy, Aarhus (Denmark) University, Denmark. These questions regard the optimal timing for treatment initiation, the role of available medications, either as monotherapy or in combination, and nonpharmacologic support options.
What’s in the toolbox?
Pulmonologists who manage PPF have a range of treatment options at their disposal. This includes careful patient observation, with treatment initiation based on clinical necessity. The therapeutic arsenal comprises immunomodulatory treatments, antifibrotic agents, palliative and supportive care, and, for a minority of patients, lung transplantation.
“Once a patient is diagnosed with PPF, it is important to remember that the diagnostic criteria from the guidelines are not exactly the same of those accepted for the reimbursement of antifibrotic treatments in different countries,” Dr. Bendstrup said, suggesting that nonclinical considerations could also potentially influence the treatment choice. She spoke at the annual congress of the European Respiratory Society.
Michael Kreuter, MD, director of the Lung Center at the University Hospital in Mainz, Germany, provided insight into the introduction of antifibrotic drugs for the treatment of PPF. Drawing from nearly a decade ago when the first antifibrotic medication was approved for idiopathic pulmonary fibrosis (IPF), Dr. Kreuter noted its effectiveness in slowing disease progression, although it does not reverse it. Subsequently, the discovery that non-IPF diseases, such as rheumatoid arthritis, exhibited IPF-like behavior led to the exploration of the use of the same drugs for similar conditions, even if not IPF.
“That’s how antifibrotic treatments came into place. Now we have more trials and data to be discussed in the future,” Dr. Kreuter added. He highlighted that antifibrotic drugs are effective for several diseases. Most of those diseases are treated with different anti-inflammatory drugs, which makes it difficult to decide when to start antifibrotic therapy and how to eventually combine it with different pharmacologic approaches.
A pivotal starting point
a question only partially addressed by existing guidelines. Dr. Bendstrup advocated for a comprehensive baseline evaluation. Factors to be considered include symptom burden, the severity of lung decline, radiologic characteristics, signs of alveolar inflammation, progression risk factors, quality of life, patient preferences, and medical history. “All these should be best discussed in a multidisciplinary team, including pulmonologists, nurses, experts in palliative care, occupational physicians, and more,” she said.
Current guidelines recommend nintedanib for PPF treatment for patients who have failed standard management for fibrotic interstitial lung disease (ILD) other than IPF. However, the definition of “standard management” remains a topic of debate, and it is acknowledged that evidence-based guidance for a standard of care varies among patients. Dr. Bendstrup pointed out the limited guidance clinicians receive from these guidelines. “As clinicians, we are not left with very much help from here.”
Choosing the right approach
Dr. Bendstrup delved into the factors influencing the choice between antifibrotic and anti-inflammatory therapies. This decision hinges on whether the patient presents with a predominantly inflammatory or a fibrotic progressive phenotype. Certain clinical characteristics contribute to the decision. Factors such as younger age, female gender, and the presence of connective tissue disease lean toward an inflammatory phenotype. Radiologic patterns, such as organized pneumonia, hypersensitivity pneumonia, or usual interstitial pneumonia–like patterns also provide valuable clues. Additionally, genetics plays a role, with shorter telomeres indicating a more fibrotic phenotype and an increased risk of immunomodulatory treatment side effects in non-IPF ILDs.
Bendstrup referred to a recent position paper on treatment recommendations and many other studies that support the use of different treatments for patients with PPF. The authors highlighted limited evidence for immunomodulation in fibrotic ILD, though such treatment is generally used except for ILD associated with systemic sclerosis. Moreover, the guidelines conditionally recommend nintedanib and call for further research on pirfenidone in PPF.
“We need intelligent, well-designed trials looking at subgroups of patients at higher risk, maybe based on molecular identification. We also need to have good biomarkers to better classify our patients based on disease behavior and treatment response. There’s a lot of discussion of biomarkers for progression, much less – if any – on biomarkers for the response to treatment. And we need them as well,” Dr. Bendstrup said in an interview.
The role of supportive care
Effective PPF treatment extends beyond pharmacologic interventions. It encompasses symptom management, patient education on vaccination and smoking cessation, and fostering social support networks. Psychological support, supplemental oxygen therapy, and pulmonary rehabilitation are integral components of care.
Elisabeth Robertson, a PPF patient representative from the United Kingdom, emphasized the importance of palliative care, not just in end-of-life scenarios but throughout the patient’s journey. Palliative care encompasses symptom alleviation, enabling patients to stay at home when possible, addressing mental health, and preparing for the end of life. Such holistic care can significantly enhance the patient’s quality of life.
The cochair of the session, Marlies S. Wijsenbeek, MD, PhD, pulmonary physician and head of the ILD Centre at the Erasmus University Medical Centre, Rotterdam, the Netherlands, underscored that palliative care begins at diagnosis and involves managing symptom burdens. “Supportive care also includes nurses, as they are precious for the patients while answering their questions and can help save time for the doctors,” she said in an interview.
In the discussion on treatment decisions, experts agreed on the pivotal role of patients in decision-making. However, Dr. Kreuter highlighted two critical factors that influence successful patient-doctor interactions: the cultural backgrounds of patients and their relatives, and the attitudes of health care providers.
Dr. Bendstrup has received honoraria or consultation fees from Boehringer Ingelheim, Roche, Astra Zeneca, Chiesi, and Daiichi Sankyo. Ms. Robertson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ERS 2023