User login
COVID-19: Can doctors refuse to see unvaccinated patients?
In June, Gerald Bock, MD, a dermatologist in central California, instituted a new office policy: He would not be seeing any more patients who remain unvaccinated against COVID-19 in his practice.
“[It is] the height of self-centered and irresponsible behavior,” he told me. “People who come in unvaccinated, when vaccination is widely available, are stating that their personal preferences are more important than their health, and are more important than any risk that they may expose their friends and family to, and also to any risk they might present to my staff and me. We have gone to considerable effort and expense to diminish any risk that visiting our office might entail. I see no reason why we should tolerate this.”
Other doctors appear to be following in his footsteps. There is no question that physicians have the right to choose their patients, just as patients are free to choose their doctors, but That is a complicated question without a clear answer. In a statement on whether physicians can decline unvaccinated patients, the American Medical Association continues to maintain that “in general” a physician may not “ethically turn a patient away based solely on the individual’s infectious disease status,” but does concede that “the decision to accept or decline a patient must balance the urgency of the individual patient’s need; the risk the patient may pose to other patients in the physician’s practice; and the need for the physician and staff, to be available to provide care in the future.”
Medical ethics experts have offered varying opinions. Daniel Wikler, PhD, professor of ethics and population health at the Harvard School of Public Health, Boston, wrote in an op-ed in the Washington Post that “ignorance or other personal failing” should not be factors in the evaluation of patients for health care. He argues that “doctors and hospitals are not in the blame and punishment business. Nor should they be. That doctors treat sinners and responsible citizens alike is a noble tradition.”
Timothy Hoff, professor of management, healthcare systems, and health policy at Northeastern University, Boston, maintains that, in nonemergency situations, physicians are legally able to refuse patients for a variety of reasons, provided they are not doing so because of some aspect of the patient’s race, gender, sexuality, or religion. However, in the same Northeastern University news release,Robert Baginski, MD, the director of interdisciplinary affairs for the department of medical sciences at Northeastern, cautions that it is vital for health authorities to continue urging the public to get vaccinated, but not at the expense of care.
Arthur L. Caplan, PhD, the head of the division of medical ethics at New York University, said in a Medscape commentary, that the decision to refuse to see patients who can vaccinate, but choose not to, is justifiable. “If you’re trying to protect yourself, your staff, or other patients, I think you do have the right to not take on somebody who won’t vaccinate,” he writes. “This is somewhat similar to when pediatricians do not accept a family if they won’t give their kids the state-required shots to go to school. That’s been happening for many years now.
“I also think it is morally justified if they won’t take your advice,” he continues. “If they won’t follow what you think is the best healthcare for them [such as getting vaccinated], there’s not much point in building that relationship.”
The situation is different in ED and hospital settings, however. “It’s a little harder to use unvaccinated status when someone really is at death’s door,” Dr. Caplan pointed out. “When someone comes in very sick, or whatever the reason, I think we have to take care of them ethically, and legally we’re bound to get them stable in the emergency room. I do think different rules apply there.”
In the end, every private practitioner will have to make his or her own decision on this question. Dr. Bock feels he made the right one. “Since instituting the policy, we have written 55 refund checks for people who had paid for a series of cosmetic procedures. We have no idea how many people were deterred from making appointments. We’ve had several negative online reviews and one woman who wrote a letter to the Medical Board of California complaining that we were discriminating against her,” he said. He added, however, that “we’ve also had several patients who commented favorably about the policy. I have no regrets about instituting the policy, and would do it again.”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
In June, Gerald Bock, MD, a dermatologist in central California, instituted a new office policy: He would not be seeing any more patients who remain unvaccinated against COVID-19 in his practice.
“[It is] the height of self-centered and irresponsible behavior,” he told me. “People who come in unvaccinated, when vaccination is widely available, are stating that their personal preferences are more important than their health, and are more important than any risk that they may expose their friends and family to, and also to any risk they might present to my staff and me. We have gone to considerable effort and expense to diminish any risk that visiting our office might entail. I see no reason why we should tolerate this.”
Other doctors appear to be following in his footsteps. There is no question that physicians have the right to choose their patients, just as patients are free to choose their doctors, but That is a complicated question without a clear answer. In a statement on whether physicians can decline unvaccinated patients, the American Medical Association continues to maintain that “in general” a physician may not “ethically turn a patient away based solely on the individual’s infectious disease status,” but does concede that “the decision to accept or decline a patient must balance the urgency of the individual patient’s need; the risk the patient may pose to other patients in the physician’s practice; and the need for the physician and staff, to be available to provide care in the future.”
Medical ethics experts have offered varying opinions. Daniel Wikler, PhD, professor of ethics and population health at the Harvard School of Public Health, Boston, wrote in an op-ed in the Washington Post that “ignorance or other personal failing” should not be factors in the evaluation of patients for health care. He argues that “doctors and hospitals are not in the blame and punishment business. Nor should they be. That doctors treat sinners and responsible citizens alike is a noble tradition.”
Timothy Hoff, professor of management, healthcare systems, and health policy at Northeastern University, Boston, maintains that, in nonemergency situations, physicians are legally able to refuse patients for a variety of reasons, provided they are not doing so because of some aspect of the patient’s race, gender, sexuality, or religion. However, in the same Northeastern University news release,Robert Baginski, MD, the director of interdisciplinary affairs for the department of medical sciences at Northeastern, cautions that it is vital for health authorities to continue urging the public to get vaccinated, but not at the expense of care.
Arthur L. Caplan, PhD, the head of the division of medical ethics at New York University, said in a Medscape commentary, that the decision to refuse to see patients who can vaccinate, but choose not to, is justifiable. “If you’re trying to protect yourself, your staff, or other patients, I think you do have the right to not take on somebody who won’t vaccinate,” he writes. “This is somewhat similar to when pediatricians do not accept a family if they won’t give their kids the state-required shots to go to school. That’s been happening for many years now.
“I also think it is morally justified if they won’t take your advice,” he continues. “If they won’t follow what you think is the best healthcare for them [such as getting vaccinated], there’s not much point in building that relationship.”
The situation is different in ED and hospital settings, however. “It’s a little harder to use unvaccinated status when someone really is at death’s door,” Dr. Caplan pointed out. “When someone comes in very sick, or whatever the reason, I think we have to take care of them ethically, and legally we’re bound to get them stable in the emergency room. I do think different rules apply there.”
In the end, every private practitioner will have to make his or her own decision on this question. Dr. Bock feels he made the right one. “Since instituting the policy, we have written 55 refund checks for people who had paid for a series of cosmetic procedures. We have no idea how many people were deterred from making appointments. We’ve had several negative online reviews and one woman who wrote a letter to the Medical Board of California complaining that we were discriminating against her,” he said. He added, however, that “we’ve also had several patients who commented favorably about the policy. I have no regrets about instituting the policy, and would do it again.”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
In June, Gerald Bock, MD, a dermatologist in central California, instituted a new office policy: He would not be seeing any more patients who remain unvaccinated against COVID-19 in his practice.
“[It is] the height of self-centered and irresponsible behavior,” he told me. “People who come in unvaccinated, when vaccination is widely available, are stating that their personal preferences are more important than their health, and are more important than any risk that they may expose their friends and family to, and also to any risk they might present to my staff and me. We have gone to considerable effort and expense to diminish any risk that visiting our office might entail. I see no reason why we should tolerate this.”
Other doctors appear to be following in his footsteps. There is no question that physicians have the right to choose their patients, just as patients are free to choose their doctors, but That is a complicated question without a clear answer. In a statement on whether physicians can decline unvaccinated patients, the American Medical Association continues to maintain that “in general” a physician may not “ethically turn a patient away based solely on the individual’s infectious disease status,” but does concede that “the decision to accept or decline a patient must balance the urgency of the individual patient’s need; the risk the patient may pose to other patients in the physician’s practice; and the need for the physician and staff, to be available to provide care in the future.”
Medical ethics experts have offered varying opinions. Daniel Wikler, PhD, professor of ethics and population health at the Harvard School of Public Health, Boston, wrote in an op-ed in the Washington Post that “ignorance or other personal failing” should not be factors in the evaluation of patients for health care. He argues that “doctors and hospitals are not in the blame and punishment business. Nor should they be. That doctors treat sinners and responsible citizens alike is a noble tradition.”
Timothy Hoff, professor of management, healthcare systems, and health policy at Northeastern University, Boston, maintains that, in nonemergency situations, physicians are legally able to refuse patients for a variety of reasons, provided they are not doing so because of some aspect of the patient’s race, gender, sexuality, or religion. However, in the same Northeastern University news release,Robert Baginski, MD, the director of interdisciplinary affairs for the department of medical sciences at Northeastern, cautions that it is vital for health authorities to continue urging the public to get vaccinated, but not at the expense of care.
Arthur L. Caplan, PhD, the head of the division of medical ethics at New York University, said in a Medscape commentary, that the decision to refuse to see patients who can vaccinate, but choose not to, is justifiable. “If you’re trying to protect yourself, your staff, or other patients, I think you do have the right to not take on somebody who won’t vaccinate,” he writes. “This is somewhat similar to when pediatricians do not accept a family if they won’t give their kids the state-required shots to go to school. That’s been happening for many years now.
“I also think it is morally justified if they won’t take your advice,” he continues. “If they won’t follow what you think is the best healthcare for them [such as getting vaccinated], there’s not much point in building that relationship.”
The situation is different in ED and hospital settings, however. “It’s a little harder to use unvaccinated status when someone really is at death’s door,” Dr. Caplan pointed out. “When someone comes in very sick, or whatever the reason, I think we have to take care of them ethically, and legally we’re bound to get them stable in the emergency room. I do think different rules apply there.”
In the end, every private practitioner will have to make his or her own decision on this question. Dr. Bock feels he made the right one. “Since instituting the policy, we have written 55 refund checks for people who had paid for a series of cosmetic procedures. We have no idea how many people were deterred from making appointments. We’ve had several negative online reviews and one woman who wrote a letter to the Medical Board of California complaining that we were discriminating against her,” he said. He added, however, that “we’ve also had several patients who commented favorably about the policy. I have no regrets about instituting the policy, and would do it again.”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Paper linking COVID-19 vaccines to myocarditis is temporarily removed without explanation
The article, “A Report on Myocarditis Adverse Events in the U.S. Vaccine Adverse Events Reporting System (VAERS) in Association with COVID-19 Injectable Biological Products,” was published in Current Problems in Cardiology, an Elsevier journal, on October 1.
It was co-authored by Jessica Rose and Peter McCullough, whose affiliations are listed as the Public Health Policy Initiative at the Institute of Pure and Applied Knowledge — a group that has been critical of vaccines and of the response to COVID-19 and has funded one study that was retracted earlier this year — and Texas A&M’s Baylor Dallas campus. [See update at the end of the post.]
Last month, Baylor Scott & White obtained a restraining order against McCullough — whom Medscape says “has promoted the use of therapies seen as unproven for the treatment of COVID-19 and has questioned the effectiveness of COVID-19 vaccines” — for continuing to refer to an affiliation with the health care institution despite a separation agreement. “Since the Baylor suit, the Texas A&M College of Medicine, and the Texas Christian University (TCU) and University of North Texas Health Science Center (UNTHSC) School of Medicine have both removed McCullough from their faculties,” Medscape reported at the time.
Here are some highlights of the now temporarily retracted paper’s claims:
Within 8 weeks of the public offering of COVID-19 products to the 12-15-year-old age group, we found 19 times the expected number of myocarditis cases in the vaccination volunteers over background myocarditis rates for this age group. In addition, a 5-fold increase in myocarditis rate was observed subsequent to dose 2 as opposed to dose 1 in 15-year-old males.
While several studies have used the VAERS database and other similar datasets around the world to estimate rates of side effects from COVID-19 vaccines, the approach has been roundly criticized and has led to at least one retraction. VAERS itself includes caution against doing so. (Another paper about myocarditis cases linked to COVID-19 vaccines has been retracted for a serious math error.)
Here’s the notice:
The Publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.
The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy .
Rose, the corresponding author of the paper, told Retraction Watch that the publisher had “applied the ‘temporary withdrawal’ label to the paper without informing us.” The publisher, Rose said, “claimed that since ‘it wasn’t an invited paper’ that they were reconsidering publishing it and hence the ‘temporary withdrawal.’”
She said the move was “unheard of” and that Elsevier was “breaching the contract we signed – all fees have been paid for gorgeous color graphics.”
Elsevier has temporarily removed more than 100 papers since 2005, by our count. The papers are often reinstated without any mention of why the paper was removed.
Hector Ventura, the editor of the journal, did not immediately respond to a request for comment.
Update, 10/17/21, 1850 UTC: Rose tells us that the correct affiliations — now noted on the temporarily retracted version — are the Institute of Pure and Applied Knowledge’s Public Health Policy Initiative (PHPI) for her, and the Truth for Health Foundation in Tucson, Ariz. for McCullough. The foundation describes it mission as:
To provide truthful, balanced, medically sound, research-based information and cutting edge updates on prevention and treatment of common medical conditions, including COVID-19 and other infectious diseases, that affect health, quality of life and longevity.
To present faith-based integrated approaches to medical treatment, health and healing services that encompass all dimensions making us human: physical, psychological/emotional, spiritual, social and environmental.
The paper was submitted before McCullough’s departure from Baylor, Rose said.
A version of this article first appeared on Retraction Watch.
The article, “A Report on Myocarditis Adverse Events in the U.S. Vaccine Adverse Events Reporting System (VAERS) in Association with COVID-19 Injectable Biological Products,” was published in Current Problems in Cardiology, an Elsevier journal, on October 1.
It was co-authored by Jessica Rose and Peter McCullough, whose affiliations are listed as the Public Health Policy Initiative at the Institute of Pure and Applied Knowledge — a group that has been critical of vaccines and of the response to COVID-19 and has funded one study that was retracted earlier this year — and Texas A&M’s Baylor Dallas campus. [See update at the end of the post.]
Last month, Baylor Scott & White obtained a restraining order against McCullough — whom Medscape says “has promoted the use of therapies seen as unproven for the treatment of COVID-19 and has questioned the effectiveness of COVID-19 vaccines” — for continuing to refer to an affiliation with the health care institution despite a separation agreement. “Since the Baylor suit, the Texas A&M College of Medicine, and the Texas Christian University (TCU) and University of North Texas Health Science Center (UNTHSC) School of Medicine have both removed McCullough from their faculties,” Medscape reported at the time.
Here are some highlights of the now temporarily retracted paper’s claims:
Within 8 weeks of the public offering of COVID-19 products to the 12-15-year-old age group, we found 19 times the expected number of myocarditis cases in the vaccination volunteers over background myocarditis rates for this age group. In addition, a 5-fold increase in myocarditis rate was observed subsequent to dose 2 as opposed to dose 1 in 15-year-old males.
While several studies have used the VAERS database and other similar datasets around the world to estimate rates of side effects from COVID-19 vaccines, the approach has been roundly criticized and has led to at least one retraction. VAERS itself includes caution against doing so. (Another paper about myocarditis cases linked to COVID-19 vaccines has been retracted for a serious math error.)
Here’s the notice:
The Publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.
The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy .
Rose, the corresponding author of the paper, told Retraction Watch that the publisher had “applied the ‘temporary withdrawal’ label to the paper without informing us.” The publisher, Rose said, “claimed that since ‘it wasn’t an invited paper’ that they were reconsidering publishing it and hence the ‘temporary withdrawal.’”
She said the move was “unheard of” and that Elsevier was “breaching the contract we signed – all fees have been paid for gorgeous color graphics.”
Elsevier has temporarily removed more than 100 papers since 2005, by our count. The papers are often reinstated without any mention of why the paper was removed.
Hector Ventura, the editor of the journal, did not immediately respond to a request for comment.
Update, 10/17/21, 1850 UTC: Rose tells us that the correct affiliations — now noted on the temporarily retracted version — are the Institute of Pure and Applied Knowledge’s Public Health Policy Initiative (PHPI) for her, and the Truth for Health Foundation in Tucson, Ariz. for McCullough. The foundation describes it mission as:
To provide truthful, balanced, medically sound, research-based information and cutting edge updates on prevention and treatment of common medical conditions, including COVID-19 and other infectious diseases, that affect health, quality of life and longevity.
To present faith-based integrated approaches to medical treatment, health and healing services that encompass all dimensions making us human: physical, psychological/emotional, spiritual, social and environmental.
The paper was submitted before McCullough’s departure from Baylor, Rose said.
A version of this article first appeared on Retraction Watch.
The article, “A Report on Myocarditis Adverse Events in the U.S. Vaccine Adverse Events Reporting System (VAERS) in Association with COVID-19 Injectable Biological Products,” was published in Current Problems in Cardiology, an Elsevier journal, on October 1.
It was co-authored by Jessica Rose and Peter McCullough, whose affiliations are listed as the Public Health Policy Initiative at the Institute of Pure and Applied Knowledge — a group that has been critical of vaccines and of the response to COVID-19 and has funded one study that was retracted earlier this year — and Texas A&M’s Baylor Dallas campus. [See update at the end of the post.]
Last month, Baylor Scott & White obtained a restraining order against McCullough — whom Medscape says “has promoted the use of therapies seen as unproven for the treatment of COVID-19 and has questioned the effectiveness of COVID-19 vaccines” — for continuing to refer to an affiliation with the health care institution despite a separation agreement. “Since the Baylor suit, the Texas A&M College of Medicine, and the Texas Christian University (TCU) and University of North Texas Health Science Center (UNTHSC) School of Medicine have both removed McCullough from their faculties,” Medscape reported at the time.
Here are some highlights of the now temporarily retracted paper’s claims:
Within 8 weeks of the public offering of COVID-19 products to the 12-15-year-old age group, we found 19 times the expected number of myocarditis cases in the vaccination volunteers over background myocarditis rates for this age group. In addition, a 5-fold increase in myocarditis rate was observed subsequent to dose 2 as opposed to dose 1 in 15-year-old males.
While several studies have used the VAERS database and other similar datasets around the world to estimate rates of side effects from COVID-19 vaccines, the approach has been roundly criticized and has led to at least one retraction. VAERS itself includes caution against doing so. (Another paper about myocarditis cases linked to COVID-19 vaccines has been retracted for a serious math error.)
Here’s the notice:
The Publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.
The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy .
Rose, the corresponding author of the paper, told Retraction Watch that the publisher had “applied the ‘temporary withdrawal’ label to the paper without informing us.” The publisher, Rose said, “claimed that since ‘it wasn’t an invited paper’ that they were reconsidering publishing it and hence the ‘temporary withdrawal.’”
She said the move was “unheard of” and that Elsevier was “breaching the contract we signed – all fees have been paid for gorgeous color graphics.”
Elsevier has temporarily removed more than 100 papers since 2005, by our count. The papers are often reinstated without any mention of why the paper was removed.
Hector Ventura, the editor of the journal, did not immediately respond to a request for comment.
Update, 10/17/21, 1850 UTC: Rose tells us that the correct affiliations — now noted on the temporarily retracted version — are the Institute of Pure and Applied Knowledge’s Public Health Policy Initiative (PHPI) for her, and the Truth for Health Foundation in Tucson, Ariz. for McCullough. The foundation describes it mission as:
To provide truthful, balanced, medically sound, research-based information and cutting edge updates on prevention and treatment of common medical conditions, including COVID-19 and other infectious diseases, that affect health, quality of life and longevity.
To present faith-based integrated approaches to medical treatment, health and healing services that encompass all dimensions making us human: physical, psychological/emotional, spiritual, social and environmental.
The paper was submitted before McCullough’s departure from Baylor, Rose said.
A version of this article first appeared on Retraction Watch.
Could your patient benefit? New trials in lung cancer
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Gut bacteria may fuel prostate cancer treatment resistance
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
U.S. arthritis prevalence continues steady rise; activity limitations grow more rapidly
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sorting out the meaning of misbehavior: The invisible culprit
You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.
Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.
While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.
Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.
Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.
Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.
Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.
Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.
The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.
Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.
Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.
While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.
Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.
Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.
Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.
Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.
Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.
The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.
Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.
Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.
While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.
Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.
Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.
Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.
Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.
Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.
The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.
Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
Few JAK inhibitor users have diminished immune response to COVID-19 vaccines
Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.
The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.
To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.
Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).
Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.
Questions about antibody levels remain difficult to answer
“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”
“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”
Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.
“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”
Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”
As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”
The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.
Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.
The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.
To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.
Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).
Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.
Questions about antibody levels remain difficult to answer
“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”
“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”
Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.
“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”
Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”
As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”
The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.
Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.
The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.
To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.
Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).
Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.
Questions about antibody levels remain difficult to answer
“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”
“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”
Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.
“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”
Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”
As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”
The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.
FROM THE LANCET RHEUMATOLOGY
Universal masking of health care workers decreases SARS-CoV-2 positivity
Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.
Study design: Retrospective cohort study.
Setting: A database of 9,850 COVID-tested health care workers in Mass General Brigham health care system from March 1 to April 30, 2020.
Synopsis: The study compared weighted mean changes in daily COVID-positive test rates between the pre-masking and post-masking time frame, allowing for a transition period between the two time frames. During the pre-masking period, the weighted mean increased by 1.16% per day. During the post-masking period, the weighted mean decreased 0.49% per day. The net slope change was 1.65% (95% CI, 1.13%-2.15%; P < .001), indicating universal masking resulted in a statistically significant decrease in the daily positive test rate among health care workers.
This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.
Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.
Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.
Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.
Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.
Study design: Retrospective cohort study.
Setting: A database of 9,850 COVID-tested health care workers in Mass General Brigham health care system from March 1 to April 30, 2020.
Synopsis: The study compared weighted mean changes in daily COVID-positive test rates between the pre-masking and post-masking time frame, allowing for a transition period between the two time frames. During the pre-masking period, the weighted mean increased by 1.16% per day. During the post-masking period, the weighted mean decreased 0.49% per day. The net slope change was 1.65% (95% CI, 1.13%-2.15%; P < .001), indicating universal masking resulted in a statistically significant decrease in the daily positive test rate among health care workers.
This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.
Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.
Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.
Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.
Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.
Study design: Retrospective cohort study.
Setting: A database of 9,850 COVID-tested health care workers in Mass General Brigham health care system from March 1 to April 30, 2020.
Synopsis: The study compared weighted mean changes in daily COVID-positive test rates between the pre-masking and post-masking time frame, allowing for a transition period between the two time frames. During the pre-masking period, the weighted mean increased by 1.16% per day. During the post-masking period, the weighted mean decreased 0.49% per day. The net slope change was 1.65% (95% CI, 1.13%-2.15%; P < .001), indicating universal masking resulted in a statistically significant decrease in the daily positive test rate among health care workers.
This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.
Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.
Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.
Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.
No advantages to using ADM in implant-based breast reconstruction
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
UC relapse associated with impaired luminal control of macrophage maturation
Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.
“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.
Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.
Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”
The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.
To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.
In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.
While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4+ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.
The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.
“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.
The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.
Current therapies for ulcerative colitis, including anti-inflammatory drugs and biologics such as anti–tumor necrosis factor therapies and anti-interleukin-12/23 antibodies, are aimed at inducing and maintaining remission. However, approximately 20%-40% of patients are primary nonresponders and about 23%-46% patients lose response within 12 months of treatment, which suggests an unmet need to look for new therapeutic targets.
Intestinal macrophages are essential in the maintenance of intestinal immune homeostasis by acquiring a hyporesponsive state in response to microbial stimuli. This study by Maasfeh and colleagues highlights the role of luminal factors in shaping the macrophage response. The authors show that human monocyte-derived macrophage treated with fecal luminal factors derived from patients with ulcerative colitis in remission are less hyporesponsive to lipopolysaccharide stimulation. They are also less efficient in modulating cytokine and Toll-like receptor signaling pathway genes and have a dampened ability to suppress CD4+ T-cell activation and interferon gamma secretion compared to controls.
Luminal factors derived from gut microbiota (short-chain fatty acids, indole derivatives, polyamines, and bile acids) can shape macrophage differentiation and antibacterial response. This study points toward key luminal factors, which might be playing pivotal roles in maintaining homeostasis. However, the current study needs further validation in a larger cohort of patients and in the lamina propria macrophages. In addition, it will be important to know the physiologically relevant concentration to achieve functional effect. The identification of specific metabolites responsible for inducing hyporesponsiveness in macrophages could be an approach for mining potential therapeutic targets.
Dr. Sumeet Pandey is in the Translational Gastroenterology Unit at John Radcliffe Hospital at the University of Oxford (England). He has no conflicts of interest.
Current therapies for ulcerative colitis, including anti-inflammatory drugs and biologics such as anti–tumor necrosis factor therapies and anti-interleukin-12/23 antibodies, are aimed at inducing and maintaining remission. However, approximately 20%-40% of patients are primary nonresponders and about 23%-46% patients lose response within 12 months of treatment, which suggests an unmet need to look for new therapeutic targets.
Intestinal macrophages are essential in the maintenance of intestinal immune homeostasis by acquiring a hyporesponsive state in response to microbial stimuli. This study by Maasfeh and colleagues highlights the role of luminal factors in shaping the macrophage response. The authors show that human monocyte-derived macrophage treated with fecal luminal factors derived from patients with ulcerative colitis in remission are less hyporesponsive to lipopolysaccharide stimulation. They are also less efficient in modulating cytokine and Toll-like receptor signaling pathway genes and have a dampened ability to suppress CD4+ T-cell activation and interferon gamma secretion compared to controls.
Luminal factors derived from gut microbiota (short-chain fatty acids, indole derivatives, polyamines, and bile acids) can shape macrophage differentiation and antibacterial response. This study points toward key luminal factors, which might be playing pivotal roles in maintaining homeostasis. However, the current study needs further validation in a larger cohort of patients and in the lamina propria macrophages. In addition, it will be important to know the physiologically relevant concentration to achieve functional effect. The identification of specific metabolites responsible for inducing hyporesponsiveness in macrophages could be an approach for mining potential therapeutic targets.
Dr. Sumeet Pandey is in the Translational Gastroenterology Unit at John Radcliffe Hospital at the University of Oxford (England). He has no conflicts of interest.
Current therapies for ulcerative colitis, including anti-inflammatory drugs and biologics such as anti–tumor necrosis factor therapies and anti-interleukin-12/23 antibodies, are aimed at inducing and maintaining remission. However, approximately 20%-40% of patients are primary nonresponders and about 23%-46% patients lose response within 12 months of treatment, which suggests an unmet need to look for new therapeutic targets.
Intestinal macrophages are essential in the maintenance of intestinal immune homeostasis by acquiring a hyporesponsive state in response to microbial stimuli. This study by Maasfeh and colleagues highlights the role of luminal factors in shaping the macrophage response. The authors show that human monocyte-derived macrophage treated with fecal luminal factors derived from patients with ulcerative colitis in remission are less hyporesponsive to lipopolysaccharide stimulation. They are also less efficient in modulating cytokine and Toll-like receptor signaling pathway genes and have a dampened ability to suppress CD4+ T-cell activation and interferon gamma secretion compared to controls.
Luminal factors derived from gut microbiota (short-chain fatty acids, indole derivatives, polyamines, and bile acids) can shape macrophage differentiation and antibacterial response. This study points toward key luminal factors, which might be playing pivotal roles in maintaining homeostasis. However, the current study needs further validation in a larger cohort of patients and in the lamina propria macrophages. In addition, it will be important to know the physiologically relevant concentration to achieve functional effect. The identification of specific metabolites responsible for inducing hyporesponsiveness in macrophages could be an approach for mining potential therapeutic targets.
Dr. Sumeet Pandey is in the Translational Gastroenterology Unit at John Radcliffe Hospital at the University of Oxford (England). He has no conflicts of interest.
Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.
“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.
Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.
Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”
The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.
To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.
In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.
While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4+ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.
The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.
“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.
The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.
Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.
“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.
Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.
Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”
The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.
To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.
In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.
While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4+ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.
The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.
“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.
The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.