It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.

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

It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.

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

It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.

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

Unlike for many other professions, there is no age limit for practicing medicine. According to international standards, airplane pilots, for example, who are responsible for the safety of many human lives, must retire by the age of 60 if they work alone, or 65 if they have a copilot. In Brazil, however, this age limit does not exist for pilots or physicians.

The only restriction on professional practice within the medical context is the mandatory retirement imposed on medical professors who teach at public (state and federal) universities, starting at the age of 75. Nevertheless, these professionals can continue practicing administrative and research-related activities. After “expulsion,” as this mandatory retirement is often called, professors who stood out or contributed to the institution and science may receive the title of professor emeritus.

In the private sector, age limits are not formally set, but the hiring of middle-aged professionals is limited.

At the Heart Institute of the University of São Paulo (Brazil) School of Medicine Clinical Hospital (InCor/HCFMUSP), one of the world’s largest teaching and research centers for cardiovascular and pulmonary diseases, several octogenarian specialists lead studies and teams. One of these is Noedir Stolf, MD, an 82-year-old cardiovascular surgeon who operates almost every day and coordinates studies on transplants, mechanical circulatory support, and aortic surgery. There is also Protásio Lemos da Luz, MD, an 82-year-old clinical cardiologist who guides research on subjects including atherosclerosis, the endothelium, microbiota, and diabetes. The protective effect of wine on atherosclerosis is one of his best-known studies.

No longer working is also not in the cards for Angelita Habr-Gama, MD, who, at 89 years old, is one of the oldest physicians in current practice. With a career spanning more than 7 decades, she is a world reference in coloproctology. She was the first woman to become a surgical resident at the HCFMUSP, where she later founded the coloproctology specialty and created the first residency program for the specialty. In April 2022, Dr. Habr-Gama joined the ranks of the 100 most influential scientists in the world, nominated by researchers at Stanford (Calif.) University, and published in PLOS Biology.

In 2020, she was sedated, intubated, and hospitalized in the intensive care unit of the Oswaldo Cruz German Hospital for 54 days because of a SARS-CoV-2 infection. After her discharge, she went back to work in less than 10 days – and added chess classes to her routine. “To get up and go to work makes me very happy. Work is my greatest hobby. No one has ever heard me complain about my life,” Dr. Habr-Gama told this news organization after having rescheduled the interview twice because of emergency surgeries.

“Doctors have a professional longevity that does not exist for other professions in which the person retires and stops practicing their profession or goes on to do something else for entertainment. Doctors can retire from one place of employment or public practice and continue practicing medicine in the office as an administrator or consultant,” Ângelo Vattimo, first secretary of the state of São Paulo Regional Board of Medicine (CREMESP), stated. The board regularly organizes a ceremony to honor professionals who have been practicing for 50 years, awarding them a certificate and engraved medal. “Many of them are around 80 years old, working and teaching. This always makes us very happy. What profession has such exceptional compliance for so long?” said Mr. Vattimo.

In the medical field, the older the age range, the smaller the number of women. According to the 2020 Medical Demographics in Brazil survey, only 2 out of 10 practicing professionals older than 70 are women.

Not everyone over 80 has Dr. Habr-Gama’s vitality, because the impact of aging is not equal. “If you look at a group of 80-year-olds, there will be much more variability than within a group of 40-year-olds,” stated Mark Katlic, MD, chief of surgery at LifeBridge Health System in the United States, who has dedicated his life to studying the subject. Dr. Katlic spoke on the subject in an interview that was published in the article “How Old Is Too Old to Work as a Doctor?” published by this news organization in April of 2022. The article discusses the evaluations of elderly physicians’ skills and competences that U.S. companies conduct. The subject has been leading to profound debate.

Dr. Katlic defends screening programs for elderly physicians, which already are in effect at the company for which he works, LifeBridge Health, and various others in the United States. “We do [screen elderly physicians at LifeBridge Health], and so do a few dozen other [U.S. institutions], but there are hundreds [of health care institutions] that do not conduct this screening,” he pointed out.

Age-related assessment faces great resistance in the United States. One physician who is against the initiative is Frank Stockdale, MD, PhD, an 86-year-old practicing oncologist affiliated with Stanford (Calif.) University Health. “It’s age discrimination ... Physicians [in the United States] receive assessments throughout their careers as part of the accreditation process – there’s no need to change that as physicians reach a certain age,” Dr. Stockdale told this news organization.

The U.S. initiative of instituting physician assessment programs for those of a certain age has even been tested in court. According to an article published in Medscape, “in New Haven, Connecticut, for instance, the U.S. Equal Employment Opportunity Commission (EEOC) filed a suit in 2020 on behalf of the Yale New Haven Hospital staff, alleging a discriminatory late career practitioner policy.”

Also, according to the article, a similar case in Minnesota reached a settlement in 2021, providing monetary relief to staff impacted by out-of-pocket costs for the assessment, in addition to requiring that the hospital in question report to the EEOC any complaints related to age discrimination.

The fact is that increased life expectancy and, subsequently, the number of middle-aged physicians in practice, has raised several questions regarding the impact of aging on professional practice. In Brazil, the subject is of interest to more than 34,571 physicians between 65 and 69 years of age and 34,237 physicians older than 70. In all, this population represents approximately 14.3% of the country’s active workforce, according to the 2020 Medical Demographics in Brazil survey.

The significant participation of health care professionals over age 50 in a survey conducted by this news organization to learn what physicians think about the age limit for practicing their professions is evidence that the subject is a present concern. Of a total of 1,641 participants, 57% were age 60 or older, 17% were between 50 and 59 years, and 12% were between 40 and 49 years. Among all participants, 51% were against these limitations, 17% approved of the idea for all specialties, and 32% believed the restriction was appropriate only for some specialties. Regarding the possibility of older physicians undergoing regular assessments, the opinions were divided: Thirty-one percent thought they should be assessed in all specialties. Furthermore, 31% believed that cognitive abilities should be regularly tested in all specialties, 31% thought this should take place for some specialties, and 38% were against this approach.

Professionals want to know, for example, how (and whether) advanced age can interfere with performance, what are the competences required to practice their activities, and if the criteria vary by specialty. “A psychiatrist doesn’t have to have perfect visual acuity, as required from a dermatologist, but it is important that they have good hearing, for example,” argued Clóvis Constantino, MD, former president of the São Paulo Regional Medical Board (CRM-SP) and former vice president of the Brazilian Federal Medical Board (CFM). “However, a surgeon has to stand for several hours in positions that may be uncomfortable. It’s not easy,” he told this news organization.

In the opinion of 82-year-old Henrique Klajner, MD, the oldest pediatrician in practice at the Albert Einstein Israeli Hospital in São Paulo, the physician cannot be subjected to the types of evaluations that have been applied in the United States. “Physicians should conduct constant self-evaluations to see if they have the competences and skills needed to practice their profession ... Moreover, this is not a matter of age. It is a matter of ethics,” said Dr. Klajner.

The ability to adapt to change and implement innovation is critical to professional longevity, he said. “Nowadays, when I admit patients, I no longer do hospital rounds, which requires a mobility equal to physical abuse for me. Therefore, I work with physicians who take care of my hospitalized patients.”

Dr. Klajner also feels there is a distinction between innovations learned through studies and what can be offered safely to patients. “If I have to care for a hospitalized patient with severe pneumonia, for example, since I am not up to date in this specialty, I am going to call upon a pulmonologist I trust and forgo my honorarium for this admission. But I will remain on the team, monitoring the patient’s progression,” he said.

During the COVID-19 pandemic, Dr. Klajner stopped seeing patients in person under the recommendation of his son, Sidney Klajner, MD, also a physician. The elder Dr. Klajner began exploring telemedicine, which opened a whole new world of possibilities. “I have conducted several online visits to provide educational instruction to mothers returning home post delivery, for example,” he told this news organization. The time to stop is not something that concerns Dr. Klajner. “I’m only going to stop when I have a really important reason to do so. For example, if I can no longer write or study, reading and rereading an article without being able to understand what is being said. At this time, none of that is happening.”

In the United States, as well as in Brazil, physicians rarely provide information to human resources departments on colleagues showing signs of cognitive or motor decline affecting their professional performance. “The expectation is that health care professionals will report colleagues with cognitive impairments, but that often does not happen,” Dr. Katlic said.

It is also not common for professionals to report their own deficits to their institutions. In large part, this is caused by a lack of well-defined policies for dealing with this issue. This news organization sought out several public and private hospitals in Brazil to see if there is any guidance on professional longevity: Most said that there is not. Only the A. C. Camargo Cancer Center reported, through its public relations team, that a committee is discussing the subject but that it is still in the early stages.

Brazilian specialist associations do not offer guidelines or instructions on the various aspects of professional longevity. Dr. Constantino tried to put the subject on the agenda during the years in which he was an administrator with the CFM. “We tried to open up discussions regarding truly elderly physicians, but the subject was not well received. I believe that it is precisely because there is a tradition of physicians working until they are no longer able that this is more difficult in Brazil ... No one exactly knows what to do in this respect.” Dr. Constantino is against the use of age as a criterion for quitting practice.

“Of course, this is a point that has to be considered, but I always defended the need for regular assessment of physicians, regardless of age range. And, although assessments are always welcome, in any profession, I also believe this would not be well received in Brazil.” He endorses an assessment of one’s knowledge and not of physical abilities, which are generally assessed through investigation when needed.

The absence of guidelines increases individual responsibility, as well as vulnerability. “Consciously, physicians will not put patients at risk if they do not have the competence to care for them or to perform a surgical procedure,” said Clystenes Odyr Soares Silva, MD, PhD, adjunct professor of pulmonology of the Federal University of São Paulo (Brazil) School of Medicine (UNIFESP). “Your peers will tell you if you are no longer able,” he added. The problem is that physicians rarely admit to or talk about their colleagues’ deficits, especially if they are in the spotlight because of advanced age. In this situation, the observation and opinion of family members regarding the health care professional’s competences and skills will hold more weight.

In case of health-related physical impairment, such as partial loss of hand movement, for example, “it is expected that this will set off an ethical warning in the person,” said Dr. Constantino. When this warning does not occur naturally, patients or colleagues can report the professional, and this may lead to the opening of an administrative investigation. If the report is found to be true, this investigation is used to suspend physicians who do not have the physical or mental ability to continue practicing medicine.

“If it’s something very serious, the physician’s license can be temporarily suspended while [the physician] is treated by a psychiatrist, with follow-up by the professional board. When discharged, the physician will get his or her [professional] license back and can go back to work,” Dr. Constantino explained. If an expert evaluation is needed, the physician will then be assessed by a forensic psychiatrist. One of the most in-demand forensic psychiatrists in Brazil is Guido Arturo Palomba, MD, 73 years old. “I have assessed some physicians for actions reported to see if they were normal people or not, but never for circumstances related to age,” Dr. Palomba said.

In practice, Brazilian medical entities do not have policies or programs to guide physicians who wish to grow old while they work or those who have started to notice they are not performing as they used to. “We have never lived as long; therefore, the quality of life in old age, as well as the concept of aging, are some of the most relevant questions of our time. These are subjects requiring additional discussion, broadening understanding and awareness in this regard,” observed Mr. Vattimo.

Dr. Constantino and Dr. Silva, who are completely against age-based assessments, believe that recertification of the specialist license every 5 years is the best path to confirming whether the physician is still able to practice. “A knowledge-based test every 5 years to recertify the specialist license has often been a topic of conversation. I think it’s an excellent idea. The person would provide a dossier of all they have done in terms of courses, conferences, and other activities, present it, and receive a score,” said Dr. Silva.

In practice, recertification of the specialist license is a topic of discussion that has been raised for years, and it is an idea that the Brazilian Medical Association (AMB) defends. In conjunction with the CFM, the association is studying a way to best implement this assessment. “It’s important to emphasize that this measure would not be retroactive at first. Instead, it would only be in effect for professionals licensed after the recertification requirement is established,” the AMB pointed out in a note sent to this news organization. Even so, the measure has faced significant resistance from a faction of the profession, and its enactment does not seem to be imminent.

The debate regarding professional longevity is taking place in various countries. In 2021, the American Medical Association Council on Medical Education released a report with a set of guidelines for the screening and assessment of physicians. The document is the product of a committee created in 2015 to study the subject. The AMA recommends that the assessment of elderly physicians be based on evidence and ethical, relevant, fair, equitable, transparent, verifiable, nonexhaustive principles, contemplating support and protecting against legal proceedings. In April of this year, a new AMA document highlighted the same principles.

Also in the United States, one of oldest initiatives created to support physicians in the process of recycling, the University of California San Diego Physician Assessment and Clinical Education Program (PACE), has a section focusing on the extended practice of medicine (Practicing Medicine Longer). For those wanting to learn more about discussions on this subject, there are online presentations on experiences in Quebec and Ontario with assessing aging physicians, neuropsychological perspectives on the aging medical population, and what to expect of healthy aging, among other subjects.

Created in 1996, PACE mostly provides services to physicians who need to address requirements of the state medical boards. Few physicians enroll on their own.

The first part of the program assesses knowledge and skills over approximately 2 days. In the second phase, the physician participates in a series of activities in a corresponding residency program. Depending on the results, the physician may have to go through a remedial program with varying activities to deal with performance deficiencies to clinical experiences at the residency level.

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

Unlike for many other professions, there is no age limit for practicing medicine. According to international standards, airplane pilots, for example, who are responsible for the safety of many human lives, must retire by the age of 60 if they work alone, or 65 if they have a copilot. In Brazil, however, this age limit does not exist for pilots or physicians.

The only restriction on professional practice within the medical context is the mandatory retirement imposed on medical professors who teach at public (state and federal) universities, starting at the age of 75. Nevertheless, these professionals can continue practicing administrative and research-related activities. After “expulsion,” as this mandatory retirement is often called, professors who stood out or contributed to the institution and science may receive the title of professor emeritus.

In the private sector, age limits are not formally set, but the hiring of middle-aged professionals is limited.

At the Heart Institute of the University of São Paulo (Brazil) School of Medicine Clinical Hospital (InCor/HCFMUSP), one of the world’s largest teaching and research centers for cardiovascular and pulmonary diseases, several octogenarian specialists lead studies and teams. One of these is Noedir Stolf, MD, an 82-year-old cardiovascular surgeon who operates almost every day and coordinates studies on transplants, mechanical circulatory support, and aortic surgery. There is also Protásio Lemos da Luz, MD, an 82-year-old clinical cardiologist who guides research on subjects including atherosclerosis, the endothelium, microbiota, and diabetes. The protective effect of wine on atherosclerosis is one of his best-known studies.

No longer working is also not in the cards for Angelita Habr-Gama, MD, who, at 89 years old, is one of the oldest physicians in current practice. With a career spanning more than 7 decades, she is a world reference in coloproctology. She was the first woman to become a surgical resident at the HCFMUSP, where she later founded the coloproctology specialty and created the first residency program for the specialty. In April 2022, Dr. Habr-Gama joined the ranks of the 100 most influential scientists in the world, nominated by researchers at Stanford (Calif.) University, and published in PLOS Biology.

In 2020, she was sedated, intubated, and hospitalized in the intensive care unit of the Oswaldo Cruz German Hospital for 54 days because of a SARS-CoV-2 infection. After her discharge, she went back to work in less than 10 days – and added chess classes to her routine. “To get up and go to work makes me very happy. Work is my greatest hobby. No one has ever heard me complain about my life,” Dr. Habr-Gama told this news organization after having rescheduled the interview twice because of emergency surgeries.

“Doctors have a professional longevity that does not exist for other professions in which the person retires and stops practicing their profession or goes on to do something else for entertainment. Doctors can retire from one place of employment or public practice and continue practicing medicine in the office as an administrator or consultant,” Ângelo Vattimo, first secretary of the state of São Paulo Regional Board of Medicine (CREMESP), stated. The board regularly organizes a ceremony to honor professionals who have been practicing for 50 years, awarding them a certificate and engraved medal. “Many of them are around 80 years old, working and teaching. This always makes us very happy. What profession has such exceptional compliance for so long?” said Mr. Vattimo.

In the medical field, the older the age range, the smaller the number of women. According to the 2020 Medical Demographics in Brazil survey, only 2 out of 10 practicing professionals older than 70 are women.

Not everyone over 80 has Dr. Habr-Gama’s vitality, because the impact of aging is not equal. “If you look at a group of 80-year-olds, there will be much more variability than within a group of 40-year-olds,” stated Mark Katlic, MD, chief of surgery at LifeBridge Health System in the United States, who has dedicated his life to studying the subject. Dr. Katlic spoke on the subject in an interview that was published in the article “How Old Is Too Old to Work as a Doctor?” published by this news organization in April of 2022. The article discusses the evaluations of elderly physicians’ skills and competences that U.S. companies conduct. The subject has been leading to profound debate.

Dr. Katlic defends screening programs for elderly physicians, which already are in effect at the company for which he works, LifeBridge Health, and various others in the United States. “We do [screen elderly physicians at LifeBridge Health], and so do a few dozen other [U.S. institutions], but there are hundreds [of health care institutions] that do not conduct this screening,” he pointed out.

Age-related assessment faces great resistance in the United States. One physician who is against the initiative is Frank Stockdale, MD, PhD, an 86-year-old practicing oncologist affiliated with Stanford (Calif.) University Health. “It’s age discrimination ... Physicians [in the United States] receive assessments throughout their careers as part of the accreditation process – there’s no need to change that as physicians reach a certain age,” Dr. Stockdale told this news organization.

The U.S. initiative of instituting physician assessment programs for those of a certain age has even been tested in court. According to an article published in Medscape, “in New Haven, Connecticut, for instance, the U.S. Equal Employment Opportunity Commission (EEOC) filed a suit in 2020 on behalf of the Yale New Haven Hospital staff, alleging a discriminatory late career practitioner policy.”

Also, according to the article, a similar case in Minnesota reached a settlement in 2021, providing monetary relief to staff impacted by out-of-pocket costs for the assessment, in addition to requiring that the hospital in question report to the EEOC any complaints related to age discrimination.

The fact is that increased life expectancy and, subsequently, the number of middle-aged physicians in practice, has raised several questions regarding the impact of aging on professional practice. In Brazil, the subject is of interest to more than 34,571 physicians between 65 and 69 years of age and 34,237 physicians older than 70. In all, this population represents approximately 14.3% of the country’s active workforce, according to the 2020 Medical Demographics in Brazil survey.

The significant participation of health care professionals over age 50 in a survey conducted by this news organization to learn what physicians think about the age limit for practicing their professions is evidence that the subject is a present concern. Of a total of 1,641 participants, 57% were age 60 or older, 17% were between 50 and 59 years, and 12% were between 40 and 49 years. Among all participants, 51% were against these limitations, 17% approved of the idea for all specialties, and 32% believed the restriction was appropriate only for some specialties. Regarding the possibility of older physicians undergoing regular assessments, the opinions were divided: Thirty-one percent thought they should be assessed in all specialties. Furthermore, 31% believed that cognitive abilities should be regularly tested in all specialties, 31% thought this should take place for some specialties, and 38% were against this approach.

Professionals want to know, for example, how (and whether) advanced age can interfere with performance, what are the competences required to practice their activities, and if the criteria vary by specialty. “A psychiatrist doesn’t have to have perfect visual acuity, as required from a dermatologist, but it is important that they have good hearing, for example,” argued Clóvis Constantino, MD, former president of the São Paulo Regional Medical Board (CRM-SP) and former vice president of the Brazilian Federal Medical Board (CFM). “However, a surgeon has to stand for several hours in positions that may be uncomfortable. It’s not easy,” he told this news organization.

In the opinion of 82-year-old Henrique Klajner, MD, the oldest pediatrician in practice at the Albert Einstein Israeli Hospital in São Paulo, the physician cannot be subjected to the types of evaluations that have been applied in the United States. “Physicians should conduct constant self-evaluations to see if they have the competences and skills needed to practice their profession ... Moreover, this is not a matter of age. It is a matter of ethics,” said Dr. Klajner.

The ability to adapt to change and implement innovation is critical to professional longevity, he said. “Nowadays, when I admit patients, I no longer do hospital rounds, which requires a mobility equal to physical abuse for me. Therefore, I work with physicians who take care of my hospitalized patients.”

Dr. Klajner also feels there is a distinction between innovations learned through studies and what can be offered safely to patients. “If I have to care for a hospitalized patient with severe pneumonia, for example, since I am not up to date in this specialty, I am going to call upon a pulmonologist I trust and forgo my honorarium for this admission. But I will remain on the team, monitoring the patient’s progression,” he said.

During the COVID-19 pandemic, Dr. Klajner stopped seeing patients in person under the recommendation of his son, Sidney Klajner, MD, also a physician. The elder Dr. Klajner began exploring telemedicine, which opened a whole new world of possibilities. “I have conducted several online visits to provide educational instruction to mothers returning home post delivery, for example,” he told this news organization. The time to stop is not something that concerns Dr. Klajner. “I’m only going to stop when I have a really important reason to do so. For example, if I can no longer write or study, reading and rereading an article without being able to understand what is being said. At this time, none of that is happening.”

In the United States, as well as in Brazil, physicians rarely provide information to human resources departments on colleagues showing signs of cognitive or motor decline affecting their professional performance. “The expectation is that health care professionals will report colleagues with cognitive impairments, but that often does not happen,” Dr. Katlic said.

It is also not common for professionals to report their own deficits to their institutions. In large part, this is caused by a lack of well-defined policies for dealing with this issue. This news organization sought out several public and private hospitals in Brazil to see if there is any guidance on professional longevity: Most said that there is not. Only the A. C. Camargo Cancer Center reported, through its public relations team, that a committee is discussing the subject but that it is still in the early stages.

Brazilian specialist associations do not offer guidelines or instructions on the various aspects of professional longevity. Dr. Constantino tried to put the subject on the agenda during the years in which he was an administrator with the CFM. “We tried to open up discussions regarding truly elderly physicians, but the subject was not well received. I believe that it is precisely because there is a tradition of physicians working until they are no longer able that this is more difficult in Brazil ... No one exactly knows what to do in this respect.” Dr. Constantino is against the use of age as a criterion for quitting practice.

“Of course, this is a point that has to be considered, but I always defended the need for regular assessment of physicians, regardless of age range. And, although assessments are always welcome, in any profession, I also believe this would not be well received in Brazil.” He endorses an assessment of one’s knowledge and not of physical abilities, which are generally assessed through investigation when needed.

The absence of guidelines increases individual responsibility, as well as vulnerability. “Consciously, physicians will not put patients at risk if they do not have the competence to care for them or to perform a surgical procedure,” said Clystenes Odyr Soares Silva, MD, PhD, adjunct professor of pulmonology of the Federal University of São Paulo (Brazil) School of Medicine (UNIFESP). “Your peers will tell you if you are no longer able,” he added. The problem is that physicians rarely admit to or talk about their colleagues’ deficits, especially if they are in the spotlight because of advanced age. In this situation, the observation and opinion of family members regarding the health care professional’s competences and skills will hold more weight.

In case of health-related physical impairment, such as partial loss of hand movement, for example, “it is expected that this will set off an ethical warning in the person,” said Dr. Constantino. When this warning does not occur naturally, patients or colleagues can report the professional, and this may lead to the opening of an administrative investigation. If the report is found to be true, this investigation is used to suspend physicians who do not have the physical or mental ability to continue practicing medicine.

“If it’s something very serious, the physician’s license can be temporarily suspended while [the physician] is treated by a psychiatrist, with follow-up by the professional board. When discharged, the physician will get his or her [professional] license back and can go back to work,” Dr. Constantino explained. If an expert evaluation is needed, the physician will then be assessed by a forensic psychiatrist. One of the most in-demand forensic psychiatrists in Brazil is Guido Arturo Palomba, MD, 73 years old. “I have assessed some physicians for actions reported to see if they were normal people or not, but never for circumstances related to age,” Dr. Palomba said.

In practice, Brazilian medical entities do not have policies or programs to guide physicians who wish to grow old while they work or those who have started to notice they are not performing as they used to. “We have never lived as long; therefore, the quality of life in old age, as well as the concept of aging, are some of the most relevant questions of our time. These are subjects requiring additional discussion, broadening understanding and awareness in this regard,” observed Mr. Vattimo.

Dr. Constantino and Dr. Silva, who are completely against age-based assessments, believe that recertification of the specialist license every 5 years is the best path to confirming whether the physician is still able to practice. “A knowledge-based test every 5 years to recertify the specialist license has often been a topic of conversation. I think it’s an excellent idea. The person would provide a dossier of all they have done in terms of courses, conferences, and other activities, present it, and receive a score,” said Dr. Silva.

In practice, recertification of the specialist license is a topic of discussion that has been raised for years, and it is an idea that the Brazilian Medical Association (AMB) defends. In conjunction with the CFM, the association is studying a way to best implement this assessment. “It’s important to emphasize that this measure would not be retroactive at first. Instead, it would only be in effect for professionals licensed after the recertification requirement is established,” the AMB pointed out in a note sent to this news organization. Even so, the measure has faced significant resistance from a faction of the profession, and its enactment does not seem to be imminent.

The debate regarding professional longevity is taking place in various countries. In 2021, the American Medical Association Council on Medical Education released a report with a set of guidelines for the screening and assessment of physicians. The document is the product of a committee created in 2015 to study the subject. The AMA recommends that the assessment of elderly physicians be based on evidence and ethical, relevant, fair, equitable, transparent, verifiable, nonexhaustive principles, contemplating support and protecting against legal proceedings. In April of this year, a new AMA document highlighted the same principles.

Also in the United States, one of oldest initiatives created to support physicians in the process of recycling, the University of California San Diego Physician Assessment and Clinical Education Program (PACE), has a section focusing on the extended practice of medicine (Practicing Medicine Longer). For those wanting to learn more about discussions on this subject, there are online presentations on experiences in Quebec and Ontario with assessing aging physicians, neuropsychological perspectives on the aging medical population, and what to expect of healthy aging, among other subjects.

Created in 1996, PACE mostly provides services to physicians who need to address requirements of the state medical boards. Few physicians enroll on their own.

The first part of the program assesses knowledge and skills over approximately 2 days. In the second phase, the physician participates in a series of activities in a corresponding residency program. Depending on the results, the physician may have to go through a remedial program with varying activities to deal with performance deficiencies to clinical experiences at the residency level.

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

Unlike for many other professions, there is no age limit for practicing medicine. According to international standards, airplane pilots, for example, who are responsible for the safety of many human lives, must retire by the age of 60 if they work alone, or 65 if they have a copilot. In Brazil, however, this age limit does not exist for pilots or physicians.

The only restriction on professional practice within the medical context is the mandatory retirement imposed on medical professors who teach at public (state and federal) universities, starting at the age of 75. Nevertheless, these professionals can continue practicing administrative and research-related activities. After “expulsion,” as this mandatory retirement is often called, professors who stood out or contributed to the institution and science may receive the title of professor emeritus.

In the private sector, age limits are not formally set, but the hiring of middle-aged professionals is limited.

At the Heart Institute of the University of São Paulo (Brazil) School of Medicine Clinical Hospital (InCor/HCFMUSP), one of the world’s largest teaching and research centers for cardiovascular and pulmonary diseases, several octogenarian specialists lead studies and teams. One of these is Noedir Stolf, MD, an 82-year-old cardiovascular surgeon who operates almost every day and coordinates studies on transplants, mechanical circulatory support, and aortic surgery. There is also Protásio Lemos da Luz, MD, an 82-year-old clinical cardiologist who guides research on subjects including atherosclerosis, the endothelium, microbiota, and diabetes. The protective effect of wine on atherosclerosis is one of his best-known studies.

No longer working is also not in the cards for Angelita Habr-Gama, MD, who, at 89 years old, is one of the oldest physicians in current practice. With a career spanning more than 7 decades, she is a world reference in coloproctology. She was the first woman to become a surgical resident at the HCFMUSP, where she later founded the coloproctology specialty and created the first residency program for the specialty. In April 2022, Dr. Habr-Gama joined the ranks of the 100 most influential scientists in the world, nominated by researchers at Stanford (Calif.) University, and published in PLOS Biology.

In 2020, she was sedated, intubated, and hospitalized in the intensive care unit of the Oswaldo Cruz German Hospital for 54 days because of a SARS-CoV-2 infection. After her discharge, she went back to work in less than 10 days – and added chess classes to her routine. “To get up and go to work makes me very happy. Work is my greatest hobby. No one has ever heard me complain about my life,” Dr. Habr-Gama told this news organization after having rescheduled the interview twice because of emergency surgeries.

“Doctors have a professional longevity that does not exist for other professions in which the person retires and stops practicing their profession or goes on to do something else for entertainment. Doctors can retire from one place of employment or public practice and continue practicing medicine in the office as an administrator or consultant,” Ângelo Vattimo, first secretary of the state of São Paulo Regional Board of Medicine (CREMESP), stated. The board regularly organizes a ceremony to honor professionals who have been practicing for 50 years, awarding them a certificate and engraved medal. “Many of them are around 80 years old, working and teaching. This always makes us very happy. What profession has such exceptional compliance for so long?” said Mr. Vattimo.

In the medical field, the older the age range, the smaller the number of women. According to the 2020 Medical Demographics in Brazil survey, only 2 out of 10 practicing professionals older than 70 are women.

Not everyone over 80 has Dr. Habr-Gama’s vitality, because the impact of aging is not equal. “If you look at a group of 80-year-olds, there will be much more variability than within a group of 40-year-olds,” stated Mark Katlic, MD, chief of surgery at LifeBridge Health System in the United States, who has dedicated his life to studying the subject. Dr. Katlic spoke on the subject in an interview that was published in the article “How Old Is Too Old to Work as a Doctor?” published by this news organization in April of 2022. The article discusses the evaluations of elderly physicians’ skills and competences that U.S. companies conduct. The subject has been leading to profound debate.

Dr. Katlic defends screening programs for elderly physicians, which already are in effect at the company for which he works, LifeBridge Health, and various others in the United States. “We do [screen elderly physicians at LifeBridge Health], and so do a few dozen other [U.S. institutions], but there are hundreds [of health care institutions] that do not conduct this screening,” he pointed out.

Age-related assessment faces great resistance in the United States. One physician who is against the initiative is Frank Stockdale, MD, PhD, an 86-year-old practicing oncologist affiliated with Stanford (Calif.) University Health. “It’s age discrimination ... Physicians [in the United States] receive assessments throughout their careers as part of the accreditation process – there’s no need to change that as physicians reach a certain age,” Dr. Stockdale told this news organization.

The U.S. initiative of instituting physician assessment programs for those of a certain age has even been tested in court. According to an article published in Medscape, “in New Haven, Connecticut, for instance, the U.S. Equal Employment Opportunity Commission (EEOC) filed a suit in 2020 on behalf of the Yale New Haven Hospital staff, alleging a discriminatory late career practitioner policy.”

Also, according to the article, a similar case in Minnesota reached a settlement in 2021, providing monetary relief to staff impacted by out-of-pocket costs for the assessment, in addition to requiring that the hospital in question report to the EEOC any complaints related to age discrimination.

The fact is that increased life expectancy and, subsequently, the number of middle-aged physicians in practice, has raised several questions regarding the impact of aging on professional practice. In Brazil, the subject is of interest to more than 34,571 physicians between 65 and 69 years of age and 34,237 physicians older than 70. In all, this population represents approximately 14.3% of the country’s active workforce, according to the 2020 Medical Demographics in Brazil survey.

The significant participation of health care professionals over age 50 in a survey conducted by this news organization to learn what physicians think about the age limit for practicing their professions is evidence that the subject is a present concern. Of a total of 1,641 participants, 57% were age 60 or older, 17% were between 50 and 59 years, and 12% were between 40 and 49 years. Among all participants, 51% were against these limitations, 17% approved of the idea for all specialties, and 32% believed the restriction was appropriate only for some specialties. Regarding the possibility of older physicians undergoing regular assessments, the opinions were divided: Thirty-one percent thought they should be assessed in all specialties. Furthermore, 31% believed that cognitive abilities should be regularly tested in all specialties, 31% thought this should take place for some specialties, and 38% were against this approach.

Professionals want to know, for example, how (and whether) advanced age can interfere with performance, what are the competences required to practice their activities, and if the criteria vary by specialty. “A psychiatrist doesn’t have to have perfect visual acuity, as required from a dermatologist, but it is important that they have good hearing, for example,” argued Clóvis Constantino, MD, former president of the São Paulo Regional Medical Board (CRM-SP) and former vice president of the Brazilian Federal Medical Board (CFM). “However, a surgeon has to stand for several hours in positions that may be uncomfortable. It’s not easy,” he told this news organization.

In the opinion of 82-year-old Henrique Klajner, MD, the oldest pediatrician in practice at the Albert Einstein Israeli Hospital in São Paulo, the physician cannot be subjected to the types of evaluations that have been applied in the United States. “Physicians should conduct constant self-evaluations to see if they have the competences and skills needed to practice their profession ... Moreover, this is not a matter of age. It is a matter of ethics,” said Dr. Klajner.

The ability to adapt to change and implement innovation is critical to professional longevity, he said. “Nowadays, when I admit patients, I no longer do hospital rounds, which requires a mobility equal to physical abuse for me. Therefore, I work with physicians who take care of my hospitalized patients.”

Dr. Klajner also feels there is a distinction between innovations learned through studies and what can be offered safely to patients. “If I have to care for a hospitalized patient with severe pneumonia, for example, since I am not up to date in this specialty, I am going to call upon a pulmonologist I trust and forgo my honorarium for this admission. But I will remain on the team, monitoring the patient’s progression,” he said.

During the COVID-19 pandemic, Dr. Klajner stopped seeing patients in person under the recommendation of his son, Sidney Klajner, MD, also a physician. The elder Dr. Klajner began exploring telemedicine, which opened a whole new world of possibilities. “I have conducted several online visits to provide educational instruction to mothers returning home post delivery, for example,” he told this news organization. The time to stop is not something that concerns Dr. Klajner. “I’m only going to stop when I have a really important reason to do so. For example, if I can no longer write or study, reading and rereading an article without being able to understand what is being said. At this time, none of that is happening.”

In the United States, as well as in Brazil, physicians rarely provide information to human resources departments on colleagues showing signs of cognitive or motor decline affecting their professional performance. “The expectation is that health care professionals will report colleagues with cognitive impairments, but that often does not happen,” Dr. Katlic said.

It is also not common for professionals to report their own deficits to their institutions. In large part, this is caused by a lack of well-defined policies for dealing with this issue. This news organization sought out several public and private hospitals in Brazil to see if there is any guidance on professional longevity: Most said that there is not. Only the A. C. Camargo Cancer Center reported, through its public relations team, that a committee is discussing the subject but that it is still in the early stages.

Brazilian specialist associations do not offer guidelines or instructions on the various aspects of professional longevity. Dr. Constantino tried to put the subject on the agenda during the years in which he was an administrator with the CFM. “We tried to open up discussions regarding truly elderly physicians, but the subject was not well received. I believe that it is precisely because there is a tradition of physicians working until they are no longer able that this is more difficult in Brazil ... No one exactly knows what to do in this respect.” Dr. Constantino is against the use of age as a criterion for quitting practice.

“Of course, this is a point that has to be considered, but I always defended the need for regular assessment of physicians, regardless of age range. And, although assessments are always welcome, in any profession, I also believe this would not be well received in Brazil.” He endorses an assessment of one’s knowledge and not of physical abilities, which are generally assessed through investigation when needed.

The absence of guidelines increases individual responsibility, as well as vulnerability. “Consciously, physicians will not put patients at risk if they do not have the competence to care for them or to perform a surgical procedure,” said Clystenes Odyr Soares Silva, MD, PhD, adjunct professor of pulmonology of the Federal University of São Paulo (Brazil) School of Medicine (UNIFESP). “Your peers will tell you if you are no longer able,” he added. The problem is that physicians rarely admit to or talk about their colleagues’ deficits, especially if they are in the spotlight because of advanced age. In this situation, the observation and opinion of family members regarding the health care professional’s competences and skills will hold more weight.

In case of health-related physical impairment, such as partial loss of hand movement, for example, “it is expected that this will set off an ethical warning in the person,” said Dr. Constantino. When this warning does not occur naturally, patients or colleagues can report the professional, and this may lead to the opening of an administrative investigation. If the report is found to be true, this investigation is used to suspend physicians who do not have the physical or mental ability to continue practicing medicine.

“If it’s something very serious, the physician’s license can be temporarily suspended while [the physician] is treated by a psychiatrist, with follow-up by the professional board. When discharged, the physician will get his or her [professional] license back and can go back to work,” Dr. Constantino explained. If an expert evaluation is needed, the physician will then be assessed by a forensic psychiatrist. One of the most in-demand forensic psychiatrists in Brazil is Guido Arturo Palomba, MD, 73 years old. “I have assessed some physicians for actions reported to see if they were normal people or not, but never for circumstances related to age,” Dr. Palomba said.

In practice, Brazilian medical entities do not have policies or programs to guide physicians who wish to grow old while they work or those who have started to notice they are not performing as they used to. “We have never lived as long; therefore, the quality of life in old age, as well as the concept of aging, are some of the most relevant questions of our time. These are subjects requiring additional discussion, broadening understanding and awareness in this regard,” observed Mr. Vattimo.

Dr. Constantino and Dr. Silva, who are completely against age-based assessments, believe that recertification of the specialist license every 5 years is the best path to confirming whether the physician is still able to practice. “A knowledge-based test every 5 years to recertify the specialist license has often been a topic of conversation. I think it’s an excellent idea. The person would provide a dossier of all they have done in terms of courses, conferences, and other activities, present it, and receive a score,” said Dr. Silva.

In practice, recertification of the specialist license is a topic of discussion that has been raised for years, and it is an idea that the Brazilian Medical Association (AMB) defends. In conjunction with the CFM, the association is studying a way to best implement this assessment. “It’s important to emphasize that this measure would not be retroactive at first. Instead, it would only be in effect for professionals licensed after the recertification requirement is established,” the AMB pointed out in a note sent to this news organization. Even so, the measure has faced significant resistance from a faction of the profession, and its enactment does not seem to be imminent.

The debate regarding professional longevity is taking place in various countries. In 2021, the American Medical Association Council on Medical Education released a report with a set of guidelines for the screening and assessment of physicians. The document is the product of a committee created in 2015 to study the subject. The AMA recommends that the assessment of elderly physicians be based on evidence and ethical, relevant, fair, equitable, transparent, verifiable, nonexhaustive principles, contemplating support and protecting against legal proceedings. In April of this year, a new AMA document highlighted the same principles.

Also in the United States, one of oldest initiatives created to support physicians in the process of recycling, the University of California San Diego Physician Assessment and Clinical Education Program (PACE), has a section focusing on the extended practice of medicine (Practicing Medicine Longer). For those wanting to learn more about discussions on this subject, there are online presentations on experiences in Quebec and Ontario with assessing aging physicians, neuropsychological perspectives on the aging medical population, and what to expect of healthy aging, among other subjects.

Created in 1996, PACE mostly provides services to physicians who need to address requirements of the state medical boards. Few physicians enroll on their own.

The first part of the program assesses knowledge and skills over approximately 2 days. In the second phase, the physician participates in a series of activities in a corresponding residency program. Depending on the results, the physician may have to go through a remedial program with varying activities to deal with performance deficiencies to clinical experiences at the residency level.

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

New research suggests there may be better times during the day for eating and fasting. 

Eating earlier in the day may help you lose weight, and eating meals within a 10-hour window could improve blood sugar and cholesterol levels, according to two new studies published in Cell Metabolism.

“You have this internal biological clock that makes you better at doing different things at different times of the day,” Courtney Peterson, PhD, an associate professor of nutrition sciences at the University of Alabama at Birmingham, told NBC News. Dr. Peterson wasn’t involved with the studies.

“It seems like the best time for your metabolism, in most people, is the mid to late morning,” she said.

In one study, researchers found that eating later in the day made people hungrier during a 24-hour period, as compared with eating the same meals earlier in the day. Late eating also burned calories at a slower rate and led to fat tissue that stored more calories. Combined, the changes may increase the risk for obesity, the study authors found.

In another study, among firefighters as shift workers, researchers found that eating meals within a 10-hour window decreased the size of bad cholesterol particles, which could reduce risk factors for heart disease. The 10-hour eating window also improved blood pressure and blood sugar levels among those with health conditions such as diabetes, high blood pressure, and high cholesterol.

The two new studies confirm findings from previous studies that indicate humans may have an ideal eating window based on the body’s circadian rhythms, which regulate sleep and wake cycles and can affect appetite, metabolism, and blood sugar levels.

In the firefighter study, for instance, the 10-hour window appears to be a “sweet spot” for the body, the authors found. More severe restrictions, as found with many intermittent fasting diets, could be difficult for the body to maintain.

“When we think about 6 or 8 hours, you might see a benefit, but people might not stick to it for a long time,” Satchidananda Panda, PhD, one of the study authors and a professor at the Salk Institute, La Jolla, Calif., told NBC News.

The new studies had small sample sizes, though they offer insight for future research. In the first study, 16 people who were overweight or obese tried two eating plans for 24-hour periods. Some of them began eating an hour after their natural wake-up time, and others waited to begin eating until about 5 hours after waking up. They ate the same meals with the same calories and nutrients.

The researchers measured their hormone levels and found that eating later decreased the levels of leptin, which helps people to feel full. Eating later also doubled the odds that people felt hungry throughout the day. Those in the study who ate later in the day also had more cravings for starchy or salty foods, as well as meat and dairy, which are energy-dense foods.

The research team also found changes in fat tissue, which could lead to a higher chance of building up new fat cells and a lower chance of burning fat. Late eaters burned about 60 fewer calories than early eaters during the day.

“Your body processes calories differently when you eat late in the day. It tips the scale in favor of weight gain and fat gain,” Dr. Peterson said. “From this study, we can get pretty clear recommendations that people shouldn’t skip breakfast.”

The second study followed 137 firefighters in San Diego who ate a Mediterranean diet with fish, vegetables, fruit, and olive oil for 12 weeks. Among those, 70 firefighters ate during a 10-hour window, and the rest ate during a longer window, generally about 13 hours. They logged their meals in an app and wore devices to track blood sugar levels.

In the 10-hour group, most firefighters ate between 8 a.m. or 9 a.m. and 6 p.m. or 7 p.m. The time-restricted eating appeared to be linked with health benefits, such as less harmful cholesterol buildup and reduced heart disease. 

Among firefighters with risk factors for heart disease, such as high blood pressure and high blood sugar, the time-restricted eating decreased their blood pressure and blood sugar levels. 

The restricted window appears to allow the body to break down toxins and get rid of sodium and other things that can drive up blood pressure and blood sugar, the authors wrote.

During periods of fasting, “organs get some rest from digesting food so they can divert their energy toward repairing cells,” Dr. Panda said.

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

New research suggests there may be better times during the day for eating and fasting. 

Eating earlier in the day may help you lose weight, and eating meals within a 10-hour window could improve blood sugar and cholesterol levels, according to two new studies published in Cell Metabolism.

“You have this internal biological clock that makes you better at doing different things at different times of the day,” Courtney Peterson, PhD, an associate professor of nutrition sciences at the University of Alabama at Birmingham, told NBC News. Dr. Peterson wasn’t involved with the studies.

“It seems like the best time for your metabolism, in most people, is the mid to late morning,” she said.

In one study, researchers found that eating later in the day made people hungrier during a 24-hour period, as compared with eating the same meals earlier in the day. Late eating also burned calories at a slower rate and led to fat tissue that stored more calories. Combined, the changes may increase the risk for obesity, the study authors found.

In another study, among firefighters as shift workers, researchers found that eating meals within a 10-hour window decreased the size of bad cholesterol particles, which could reduce risk factors for heart disease. The 10-hour eating window also improved blood pressure and blood sugar levels among those with health conditions such as diabetes, high blood pressure, and high cholesterol.

The two new studies confirm findings from previous studies that indicate humans may have an ideal eating window based on the body’s circadian rhythms, which regulate sleep and wake cycles and can affect appetite, metabolism, and blood sugar levels.

In the firefighter study, for instance, the 10-hour window appears to be a “sweet spot” for the body, the authors found. More severe restrictions, as found with many intermittent fasting diets, could be difficult for the body to maintain.

“When we think about 6 or 8 hours, you might see a benefit, but people might not stick to it for a long time,” Satchidananda Panda, PhD, one of the study authors and a professor at the Salk Institute, La Jolla, Calif., told NBC News.

The new studies had small sample sizes, though they offer insight for future research. In the first study, 16 people who were overweight or obese tried two eating plans for 24-hour periods. Some of them began eating an hour after their natural wake-up time, and others waited to begin eating until about 5 hours after waking up. They ate the same meals with the same calories and nutrients.

The researchers measured their hormone levels and found that eating later decreased the levels of leptin, which helps people to feel full. Eating later also doubled the odds that people felt hungry throughout the day. Those in the study who ate later in the day also had more cravings for starchy or salty foods, as well as meat and dairy, which are energy-dense foods.

The research team also found changes in fat tissue, which could lead to a higher chance of building up new fat cells and a lower chance of burning fat. Late eaters burned about 60 fewer calories than early eaters during the day.

“Your body processes calories differently when you eat late in the day. It tips the scale in favor of weight gain and fat gain,” Dr. Peterson said. “From this study, we can get pretty clear recommendations that people shouldn’t skip breakfast.”

The second study followed 137 firefighters in San Diego who ate a Mediterranean diet with fish, vegetables, fruit, and olive oil for 12 weeks. Among those, 70 firefighters ate during a 10-hour window, and the rest ate during a longer window, generally about 13 hours. They logged their meals in an app and wore devices to track blood sugar levels.

In the 10-hour group, most firefighters ate between 8 a.m. or 9 a.m. and 6 p.m. or 7 p.m. The time-restricted eating appeared to be linked with health benefits, such as less harmful cholesterol buildup and reduced heart disease. 

Among firefighters with risk factors for heart disease, such as high blood pressure and high blood sugar, the time-restricted eating decreased their blood pressure and blood sugar levels. 

The restricted window appears to allow the body to break down toxins and get rid of sodium and other things that can drive up blood pressure and blood sugar, the authors wrote.

During periods of fasting, “organs get some rest from digesting food so they can divert their energy toward repairing cells,” Dr. Panda said.

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

New research suggests there may be better times during the day for eating and fasting. 

Eating earlier in the day may help you lose weight, and eating meals within a 10-hour window could improve blood sugar and cholesterol levels, according to two new studies published in Cell Metabolism.

“You have this internal biological clock that makes you better at doing different things at different times of the day,” Courtney Peterson, PhD, an associate professor of nutrition sciences at the University of Alabama at Birmingham, told NBC News. Dr. Peterson wasn’t involved with the studies.

“It seems like the best time for your metabolism, in most people, is the mid to late morning,” she said.

In one study, researchers found that eating later in the day made people hungrier during a 24-hour period, as compared with eating the same meals earlier in the day. Late eating also burned calories at a slower rate and led to fat tissue that stored more calories. Combined, the changes may increase the risk for obesity, the study authors found.

In another study, among firefighters as shift workers, researchers found that eating meals within a 10-hour window decreased the size of bad cholesterol particles, which could reduce risk factors for heart disease. The 10-hour eating window also improved blood pressure and blood sugar levels among those with health conditions such as diabetes, high blood pressure, and high cholesterol.

The two new studies confirm findings from previous studies that indicate humans may have an ideal eating window based on the body’s circadian rhythms, which regulate sleep and wake cycles and can affect appetite, metabolism, and blood sugar levels.

In the firefighter study, for instance, the 10-hour window appears to be a “sweet spot” for the body, the authors found. More severe restrictions, as found with many intermittent fasting diets, could be difficult for the body to maintain.

“When we think about 6 or 8 hours, you might see a benefit, but people might not stick to it for a long time,” Satchidananda Panda, PhD, one of the study authors and a professor at the Salk Institute, La Jolla, Calif., told NBC News.

The new studies had small sample sizes, though they offer insight for future research. In the first study, 16 people who were overweight or obese tried two eating plans for 24-hour periods. Some of them began eating an hour after their natural wake-up time, and others waited to begin eating until about 5 hours after waking up. They ate the same meals with the same calories and nutrients.

The researchers measured their hormone levels and found that eating later decreased the levels of leptin, which helps people to feel full. Eating later also doubled the odds that people felt hungry throughout the day. Those in the study who ate later in the day also had more cravings for starchy or salty foods, as well as meat and dairy, which are energy-dense foods.

The research team also found changes in fat tissue, which could lead to a higher chance of building up new fat cells and a lower chance of burning fat. Late eaters burned about 60 fewer calories than early eaters during the day.

“Your body processes calories differently when you eat late in the day. It tips the scale in favor of weight gain and fat gain,” Dr. Peterson said. “From this study, we can get pretty clear recommendations that people shouldn’t skip breakfast.”

The second study followed 137 firefighters in San Diego who ate a Mediterranean diet with fish, vegetables, fruit, and olive oil for 12 weeks. Among those, 70 firefighters ate during a 10-hour window, and the rest ate during a longer window, generally about 13 hours. They logged their meals in an app and wore devices to track blood sugar levels.

In the 10-hour group, most firefighters ate between 8 a.m. or 9 a.m. and 6 p.m. or 7 p.m. The time-restricted eating appeared to be linked with health benefits, such as less harmful cholesterol buildup and reduced heart disease. 

Among firefighters with risk factors for heart disease, such as high blood pressure and high blood sugar, the time-restricted eating decreased their blood pressure and blood sugar levels. 

The restricted window appears to allow the body to break down toxins and get rid of sodium and other things that can drive up blood pressure and blood sugar, the authors wrote.

During periods of fasting, “organs get some rest from digesting food so they can divert their energy toward repairing cells,” Dr. Panda said.

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

Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

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

Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

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

Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

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

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Restriction of dietary salt to alleviate or prevent volume overload in patients with acute decompensated heart failure (ADHF) is common hospital practice, but without a solid evidence base. A trial testing whether taking salt pills might have benefits for patients with ADHF undergoing intensive diuresis, therefore, may seem a bit counterintuitive.

In just such a randomized, placebo-controlled trial, the approach made no difference to weight loss on diuresis, a proxy for volume reduction, or to serum creatinine levels in ADHF patients receiving high-dose intravenous diuretic therapy.

Georges Lievre / Fotolia.com

The patients consumed the extra salt during their intravenous therapy in the form of tablets providing 6 g sodium chloride daily on top of their hospital-provided, low-sodium meals.

During that time, serum sodium levels remained stable for the 34 patients assigned to the salt tablets but dropped significantly in the 31 given placebo pills.

They lost about the same weight, averages of 4 kg and 4.6 kg (8.8-10 lb), respectively, and their urine output was also similar. Patients who took the salt tablets showed less of an increase in blood urea nitrogen (BUN) at both 96 hours and at discharge.

The findings “challenge the routine practice of sodium chloride restriction in acute heart failure, something done thousands of times a day, millions of times a year,” Robert A. Montgomery, MD, Cleveland Clinic, said when presenting the study at the annual scientific meeting of the Heart Failure Society of America.

The trial, called OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure), also may encourage a shift in ADHF management from a preoccupation with salt restriction to focus more on fighting fluid retention.

OSPREY-HF took on “an established practice that doesn’t have much high-quality evidentiary support,” one guided primarily by consensus and observational data, Montgomery said in an interview.

There are also potential downsides to dietary sodium restriction, including some that may complicate or block ADHF therapies.

“Low-sodium diets can be associated with decreased caloric intake and nutritional quality,” Dr. Montgomery observed. And observational studies suggest that “patients who are on a low sodium diet can develop increased neurohormonal activation. The kidney is not sensing salt, and so starts ramping up the hormones,” which promotes diuretic resistance.

But emerging evidence also suggests “that giving sodium chloride in the form of hypertonic saline can help patients who are diuretic resistant.” The intervention, which appears to attenuate the neurohormonal activation associated with high-dose intravenous diuretics, Dr. Montgomery noted, helped inspire the design of OSPREY-AHF.

Edema consists of “a gallon of water and a pinch of salt, so we really should stop being so salt-centric and think much more about water as the problem in decompensated heart failure,” said John G.F. Cleland, MD, PhD, during the question-and-answer period after Montgomery’s presentation. Dr. Cleland, of the University of Glasgow Institute of Health and Wellbeing, is not connected to OSPREY-AHF.

“I think that maybe we overinterpret how important salt is” as a focus of volume management in ADHF, offered David Lanfear, MD, Henry Ford Health System, Detroit, who is also not part of the study.

OSPREY-AHF was well conducted but applies to a “very specific” clinical setting, Dr. Lanfear said in an interview. “These people are getting aggressive diuresis, a big dose and continuous infusion. It’s not everybody that has heart failure.”

Although the study was small, “I think it will fuel interest in this area and, probably, further investigation,” he said. The trial on its own won’t change practice, “but it will raise some eyebrows.”

The trial included patients with ADHF who have been “admitted to a cardiovascular medicine floor, not the intensive care unit” and were receiving at least 10 mg per hour of furosemide. It excluded any who were “hypernatremic or severely hyponatremic,” said Dr. Montgomery when presenting the study. They were required to have an initial estimated glomerular filtration rate (eGFR) of at least 15 mL/min per 1.73 m².

The patients were randomly assigned double blind at a single center to receive tablets providing 2 g sodium chloride or placebo pills – 34 and 31 patients, respectively – three times daily during intravenous diuresis.

At 96 hours, the two groups showed no difference in change in creatinine levels or change in weight, both primary endpoints. Nor did they differ in urine output or change in eGFR. But serum sodium levels fell further, and BUN levels went up more in those given placebo.

The two groups showed no differences in hospital length of stay, use of renal replacement therapy at 90 days, ICU time during the index hospitalization, 30-day readmission, or 90-day mortality – although the trial wasn’t powered for clinical outcomes, Dr. Montgomery reported.

"We have patients who complain about their sodium-restricted diet, we have patients that have cachexia, who have a lot of complaints about provider-ordered meals and recommendations,” Dr. Montgomery explained in an interview.

Clinicians provide education and invest a lot of effort into getting patients with heart failure to start and maintain a low-sodium diet, he said. “But a low-sodium diet, in prior studies – and our study adds to this – is not a lever that actually seems to positively or adversely affect patients.”

Dr. Montgomery pointed to the recently published SODIUM-HF trial comparing low-sodium and unrestricted-sodium diets in outpatients with heart failure. It saw no clinical benefit from the low-sodium intervention.

Until studies show, potentially, that sodium restriction in hospitalized patients with heart failure makes a clinical difference, Dr. Montgomery said, “I’d say we should invest our time in things that we know are the most helpful, like getting them on guideline-directed medical therapy, when instead we spend an enormous amount of time counseling on and enforcing dietary restriction.”

Support for this study was provided by Cleveland Clinic Heart Vascular and Thoracic Institute’s Wilson Grant and Kaufman Center for Heart Failure Treatment and Recovery Grant. Dr. Lanfear disclosed research support from SomaLogic and Lilly; consulting for Abbott Laboratories, AstraZeneca, Janssen, Martin Pharmaceuticals, and Amgen; and serving on advisory panels for Illumina and Cytokinetics. Dr. Montgomery and Dr. Cleland disclosed no relevant financial relationships.

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

Physician authors of clinical practice guidelines for psoriatic arthritis in the United States and Japan received payments from pharmaceutical companies totaling over $7 million during 2016-2018, according to a retrospective analysis of all authors on the most recent guidelines issued by the American College of Rheumatology (ACR) and the Japanese Dermatological Association (JDA).

In addition to finding that the majority of the authors of psoriatic arthritis (PsA) clinical practice guidelines (CPGs) issued by the JDA and ACR received substantial personal payments from pharmaceutical companies before and during CPG development, researchers led by Hanano Mamada and Anju Murayama of the Medical Governance Research Institute, Tokyo, wrote in Arthritis Care & Research that “several CPG authors self-cited their articles without the disclosure of NFCOI [nonfinancial conflicts of interest], and most of the recommendations were based on low or very low quality of evidence. Although the COI policies used by JDA and ACR are clearly inadequate, no significant revisions have been made for the last 3 years.”

Based on their findings, which were made using payment data from major Japanese pharmaceutical companies and the U.S. Open Payments Database from 2016 to 2018, the researchers suggested that the medical societies should:

• Adopt global standard COI policies from organizations such as the National Academy of Medicine and Guidelines International Network, including a 3-year lookback period for COI declaration.
• Consider a comprehensive definition and rigorous management with full disclosure of NFCOI.
• Publish a list of authors making each recommendation to grasp the implications of COI in clinical practice guidelines.
• Mention the detailed date of the COI disclosure, which should be close to the publication date as much as possible.

Financial conflicts of interest

The researchers used payment data published between 2016 and 2018 for all 83 companies belonging to the Japan Pharmaceutical Manufacturers Association, focusing on personal payments (for lecturing, writing, and consultancy) and excluding research payments, “since in Japan, the name, institution, and position of the author or researcher who received the research payment is not disclosed, which makes assessing research payments difficult.” To evaluate authors’ FCOI in the ACR’s CPG, the researchers analyzed the U.S. Open Payments Database “for all categories of general payments such as speaking, consulting, meals, and travel expenses 3 years from before the guideline’s first online publication on November 30, 2018.”

The 2018 ACR/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis had 36 authors and the JDA’s Clinical Practice Guideline for the Treatment of Psoriatic Arthritis 2019 had 23. Overall, 61% of JDA authors and half of ACR authors voluntarily declared FCOI with pharmaceutical companies; 25 of the ACR authors were U.S. physicians and could be included in the Open Payments Database search.

A total of 21 (91.3%) JDA authors and 21 (84.0%) ACR authors received at least one payment, with the combined total of $3,335,413 and $4,081,629 payments, respectively, over the 3 years. The average and median personal payments were $145,018 and $123,876 for JDA authors and $162,825 and $58,826 for ACR authors. When the payments to ACR authors were limited to lecturing, writing, and consulting fees that are required under the ACR’s COI policy, the mean was $130,102 and median was $39,375. The corresponding payments for JDA authors were $123,876 and $8,170, respectively,

The researchers found undisclosed payments for more than three-quarters of physician authors of the Japanese guideline, and nearly half of the doctors authoring the American guideline had undisclosed payments. These added up to $474,000 for the JDA, which amounted to 38% of the total for personal payments that must be reported to the JDA based on its COI policy for clinical practice guidelines, and $218,000 for the ACR, amounting to 18% of the total for personal payments that must be reported to the society based on its COI policy.

Of the 11 ACR authors who were not eligible for the U.S. Open Payments Database search, 5 declared FCOI with pharmaceutical companies in the guideline, meaning that 26 (72%) of the 36 authors had FCOI with pharmaceutical companies.

The ACR only required authors to declare FCOI covering 1 year before and during guideline development, and although the JDA required authors to declare their FCOI for the past 3 years of guideline development, the study authors noted that the JDA guideline disclosed them for only 2 years (between Jan. 1, 2017, and Dec. 31, 2018).

“It is true that influential doctors such as clinical practice guideline authors tend to receive various types of payments from pharmaceutical companies and that it is difficult to conduct research without funding from pharmaceutical companies. However, our current research mainly focuses on personal payments from pharmaceutical companies such as lecture fees and consulting fees. These payments are recognized as pocket money and are not used for research. Thus, it is questionable that the observed relationships are something evitable,” the researchers wrote.
 

Nonfinancial conflicts of interest

Many authors of the ACR’s CPG and the JDA’s CPG also had NFCOI, defined objectively in this study as self-citation rate. NFCOI have been more broadly defined by the International Committee of Medical Journal Editors (ICMJE) as “conflicts, such as personal relationships or rivalries, academic competition, and intellectual beliefs”; the ICMJE recommends reporting NFCOI on its COI form.

The JDA guideline included self-citations by 78% of its authors, compared with 32% of the ACR guideline authors, but this weighed differently among the two guidelines in that only 12 of the 354 (3.4%) citations in the JDA guideline were self-cited, compared with 46 of 137 (34%) citations in the ACR guideline.

The researchers noted that while the self-citation rates between JDA and ACR authors “differed remarkably,” the impact of ACR authors on CPG recommendations was much more direct. Three-quarters of JDA authors’ self-cited articles were about observational studies, whereas 52% of the ACR authors’ self-cited articles were clinical trials, most of which were randomized, controlled studies, and these NFCOI were not disclosed in the guideline.

Half of the strong recommendations in the JDA guideline were based on low or very low quality of evidence, whereas the ACR guideline had no strong recommendations based on low or very low quality of evidence.

This study was supported by the nonprofit Medical Governance Research Institute, which receives donations from Ain Pharmacies Inc., other organizations, and private individuals. The study also received support from the Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. Three authors reported receiving personal fees from several pharmaceutical companies for work outside of the scope of this study.

Physician authors of clinical practice guidelines for psoriatic arthritis in the United States and Japan received payments from pharmaceutical companies totaling over $7 million during 2016-2018, according to a retrospective analysis of all authors on the most recent guidelines issued by the American College of Rheumatology (ACR) and the Japanese Dermatological Association (JDA).

In addition to finding that the majority of the authors of psoriatic arthritis (PsA) clinical practice guidelines (CPGs) issued by the JDA and ACR received substantial personal payments from pharmaceutical companies before and during CPG development, researchers led by Hanano Mamada and Anju Murayama of the Medical Governance Research Institute, Tokyo, wrote in Arthritis Care & Research that “several CPG authors self-cited their articles without the disclosure of NFCOI [nonfinancial conflicts of interest], and most of the recommendations were based on low or very low quality of evidence. Although the COI policies used by JDA and ACR are clearly inadequate, no significant revisions have been made for the last 3 years.”

Based on their findings, which were made using payment data from major Japanese pharmaceutical companies and the U.S. Open Payments Database from 2016 to 2018, the researchers suggested that the medical societies should:

• Adopt global standard COI policies from organizations such as the National Academy of Medicine and Guidelines International Network, including a 3-year lookback period for COI declaration.
• Consider a comprehensive definition and rigorous management with full disclosure of NFCOI.
• Publish a list of authors making each recommendation to grasp the implications of COI in clinical practice guidelines.
• Mention the detailed date of the COI disclosure, which should be close to the publication date as much as possible.

Financial conflicts of interest

The researchers used payment data published between 2016 and 2018 for all 83 companies belonging to the Japan Pharmaceutical Manufacturers Association, focusing on personal payments (for lecturing, writing, and consultancy) and excluding research payments, “since in Japan, the name, institution, and position of the author or researcher who received the research payment is not disclosed, which makes assessing research payments difficult.” To evaluate authors’ FCOI in the ACR’s CPG, the researchers analyzed the U.S. Open Payments Database “for all categories of general payments such as speaking, consulting, meals, and travel expenses 3 years from before the guideline’s first online publication on November 30, 2018.”

The 2018 ACR/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis had 36 authors and the JDA’s Clinical Practice Guideline for the Treatment of Psoriatic Arthritis 2019 had 23. Overall, 61% of JDA authors and half of ACR authors voluntarily declared FCOI with pharmaceutical companies; 25 of the ACR authors were U.S. physicians and could be included in the Open Payments Database search.

A total of 21 (91.3%) JDA authors and 21 (84.0%) ACR authors received at least one payment, with the combined total of $3,335,413 and $4,081,629 payments, respectively, over the 3 years. The average and median personal payments were $145,018 and $123,876 for JDA authors and $162,825 and $58,826 for ACR authors. When the payments to ACR authors were limited to lecturing, writing, and consulting fees that are required under the ACR’s COI policy, the mean was $130,102 and median was $39,375. The corresponding payments for JDA authors were $123,876 and $8,170, respectively,

The researchers found undisclosed payments for more than three-quarters of physician authors of the Japanese guideline, and nearly half of the doctors authoring the American guideline had undisclosed payments. These added up to $474,000 for the JDA, which amounted to 38% of the total for personal payments that must be reported to the JDA based on its COI policy for clinical practice guidelines, and $218,000 for the ACR, amounting to 18% of the total for personal payments that must be reported to the society based on its COI policy.

Of the 11 ACR authors who were not eligible for the U.S. Open Payments Database search, 5 declared FCOI with pharmaceutical companies in the guideline, meaning that 26 (72%) of the 36 authors had FCOI with pharmaceutical companies.

The ACR only required authors to declare FCOI covering 1 year before and during guideline development, and although the JDA required authors to declare their FCOI for the past 3 years of guideline development, the study authors noted that the JDA guideline disclosed them for only 2 years (between Jan. 1, 2017, and Dec. 31, 2018).

“It is true that influential doctors such as clinical practice guideline authors tend to receive various types of payments from pharmaceutical companies and that it is difficult to conduct research without funding from pharmaceutical companies. However, our current research mainly focuses on personal payments from pharmaceutical companies such as lecture fees and consulting fees. These payments are recognized as pocket money and are not used for research. Thus, it is questionable that the observed relationships are something evitable,” the researchers wrote.
 

Nonfinancial conflicts of interest

Many authors of the ACR’s CPG and the JDA’s CPG also had NFCOI, defined objectively in this study as self-citation rate. NFCOI have been more broadly defined by the International Committee of Medical Journal Editors (ICMJE) as “conflicts, such as personal relationships or rivalries, academic competition, and intellectual beliefs”; the ICMJE recommends reporting NFCOI on its COI form.

The JDA guideline included self-citations by 78% of its authors, compared with 32% of the ACR guideline authors, but this weighed differently among the two guidelines in that only 12 of the 354 (3.4%) citations in the JDA guideline were self-cited, compared with 46 of 137 (34%) citations in the ACR guideline.

The researchers noted that while the self-citation rates between JDA and ACR authors “differed remarkably,” the impact of ACR authors on CPG recommendations was much more direct. Three-quarters of JDA authors’ self-cited articles were about observational studies, whereas 52% of the ACR authors’ self-cited articles were clinical trials, most of which were randomized, controlled studies, and these NFCOI were not disclosed in the guideline.

Half of the strong recommendations in the JDA guideline were based on low or very low quality of evidence, whereas the ACR guideline had no strong recommendations based on low or very low quality of evidence.

This study was supported by the nonprofit Medical Governance Research Institute, which receives donations from Ain Pharmacies Inc., other organizations, and private individuals. The study also received support from the Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. Three authors reported receiving personal fees from several pharmaceutical companies for work outside of the scope of this study.

Physician authors of clinical practice guidelines for psoriatic arthritis in the United States and Japan received payments from pharmaceutical companies totaling over $7 million during 2016-2018, according to a retrospective analysis of all authors on the most recent guidelines issued by the American College of Rheumatology (ACR) and the Japanese Dermatological Association (JDA).

In addition to finding that the majority of the authors of psoriatic arthritis (PsA) clinical practice guidelines (CPGs) issued by the JDA and ACR received substantial personal payments from pharmaceutical companies before and during CPG development, researchers led by Hanano Mamada and Anju Murayama of the Medical Governance Research Institute, Tokyo, wrote in Arthritis Care & Research that “several CPG authors self-cited their articles without the disclosure of NFCOI [nonfinancial conflicts of interest], and most of the recommendations were based on low or very low quality of evidence. Although the COI policies used by JDA and ACR are clearly inadequate, no significant revisions have been made for the last 3 years.”

Based on their findings, which were made using payment data from major Japanese pharmaceutical companies and the U.S. Open Payments Database from 2016 to 2018, the researchers suggested that the medical societies should:

• Adopt global standard COI policies from organizations such as the National Academy of Medicine and Guidelines International Network, including a 3-year lookback period for COI declaration.
• Consider a comprehensive definition and rigorous management with full disclosure of NFCOI.
• Publish a list of authors making each recommendation to grasp the implications of COI in clinical practice guidelines.
• Mention the detailed date of the COI disclosure, which should be close to the publication date as much as possible.

Financial conflicts of interest

The researchers used payment data published between 2016 and 2018 for all 83 companies belonging to the Japan Pharmaceutical Manufacturers Association, focusing on personal payments (for lecturing, writing, and consultancy) and excluding research payments, “since in Japan, the name, institution, and position of the author or researcher who received the research payment is not disclosed, which makes assessing research payments difficult.” To evaluate authors’ FCOI in the ACR’s CPG, the researchers analyzed the U.S. Open Payments Database “for all categories of general payments such as speaking, consulting, meals, and travel expenses 3 years from before the guideline’s first online publication on November 30, 2018.”

The 2018 ACR/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis had 36 authors and the JDA’s Clinical Practice Guideline for the Treatment of Psoriatic Arthritis 2019 had 23. Overall, 61% of JDA authors and half of ACR authors voluntarily declared FCOI with pharmaceutical companies; 25 of the ACR authors were U.S. physicians and could be included in the Open Payments Database search.

A total of 21 (91.3%) JDA authors and 21 (84.0%) ACR authors received at least one payment, with the combined total of $3,335,413 and $4,081,629 payments, respectively, over the 3 years. The average and median personal payments were $145,018 and $123,876 for JDA authors and $162,825 and $58,826 for ACR authors. When the payments to ACR authors were limited to lecturing, writing, and consulting fees that are required under the ACR’s COI policy, the mean was $130,102 and median was $39,375. The corresponding payments for JDA authors were $123,876 and $8,170, respectively,

The researchers found undisclosed payments for more than three-quarters of physician authors of the Japanese guideline, and nearly half of the doctors authoring the American guideline had undisclosed payments. These added up to $474,000 for the JDA, which amounted to 38% of the total for personal payments that must be reported to the JDA based on its COI policy for clinical practice guidelines, and $218,000 for the ACR, amounting to 18% of the total for personal payments that must be reported to the society based on its COI policy.

Of the 11 ACR authors who were not eligible for the U.S. Open Payments Database search, 5 declared FCOI with pharmaceutical companies in the guideline, meaning that 26 (72%) of the 36 authors had FCOI with pharmaceutical companies.

The ACR only required authors to declare FCOI covering 1 year before and during guideline development, and although the JDA required authors to declare their FCOI for the past 3 years of guideline development, the study authors noted that the JDA guideline disclosed them for only 2 years (between Jan. 1, 2017, and Dec. 31, 2018).

“It is true that influential doctors such as clinical practice guideline authors tend to receive various types of payments from pharmaceutical companies and that it is difficult to conduct research without funding from pharmaceutical companies. However, our current research mainly focuses on personal payments from pharmaceutical companies such as lecture fees and consulting fees. These payments are recognized as pocket money and are not used for research. Thus, it is questionable that the observed relationships are something evitable,” the researchers wrote.
 

Nonfinancial conflicts of interest

Many authors of the ACR’s CPG and the JDA’s CPG also had NFCOI, defined objectively in this study as self-citation rate. NFCOI have been more broadly defined by the International Committee of Medical Journal Editors (ICMJE) as “conflicts, such as personal relationships or rivalries, academic competition, and intellectual beliefs”; the ICMJE recommends reporting NFCOI on its COI form.

The JDA guideline included self-citations by 78% of its authors, compared with 32% of the ACR guideline authors, but this weighed differently among the two guidelines in that only 12 of the 354 (3.4%) citations in the JDA guideline were self-cited, compared with 46 of 137 (34%) citations in the ACR guideline.

The researchers noted that while the self-citation rates between JDA and ACR authors “differed remarkably,” the impact of ACR authors on CPG recommendations was much more direct. Three-quarters of JDA authors’ self-cited articles were about observational studies, whereas 52% of the ACR authors’ self-cited articles were clinical trials, most of which were randomized, controlled studies, and these NFCOI were not disclosed in the guideline.

Half of the strong recommendations in the JDA guideline were based on low or very low quality of evidence, whereas the ACR guideline had no strong recommendations based on low or very low quality of evidence.

This study was supported by the nonprofit Medical Governance Research Institute, which receives donations from Ain Pharmacies Inc., other organizations, and private individuals. The study also received support from the Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. Three authors reported receiving personal fees from several pharmaceutical companies for work outside of the scope of this study.

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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

To be cost effective, compared with metformin, for initial therapy for type 2 diabetes, prices for a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist would have to fall by at least 70% and at least 90%, respectively, according to estimates.

Thinkstock Photos

The study, modeled on U.S. patients, by Jin G. Choi, MD, and colleagues, was published online Oct. 3 in the Annals of Internal Medicine.

The researchers simulated the lifetime incidence, prevalence, mortality, and costs associated with three different first-line treatment strategies – metformin, an SGLT2 inhibitor, or a GLP-1 agonist – in U.S. patients with untreated type 2 diabetes.

Compared with patients who received initial treatment with metformin, those who received one of the newer drugs had 4.4% to 5.2% lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke.

However, to be cost-effective at under $150,000 per quality-adjusted life-years (QALY), SGLT2 inhibitors would need to cost less than $5 a day ($1,800 a year), and GLP-1 agonists would have to cost less than $6 a day ($2,100 a year), a lot less than now.

Knowing how expensive these drugs are, “I am not surprised” that the model predicts that the price would have to drop so much to make them cost-effective, compared with first-line treatment with metformin, senior author Neda Laiteerapong, MD, said in an interview.

“But I am disappointed,” she said, because these drugs are very effective, and if the prices were lower, more people could benefit.

“In the interest of improving access to high-quality care in the United States, our study results indicate the need to reduce SGLT2 inhibitor and GLP-1 receptor agonist medication costs substantially for patients with type 2 [diabetes] to improve health outcomes and prevent exacerbating diabetes health disparities,” the researchers conclude.

One way that the newer drugs might be more widely affordable is if the government became involved, possibly by passing a law similar to the Affordable Insulin Now Act, speculated Dr. Laiteerapong, who is associate director at the Center for Chronic Disease Research and Policy, University of Chicago.
 

‘Current prices too high to encourage first-line adoption’

Guidelines recommend the use of SGLT2 inhibitors and GLP-1 agonists as second-line therapies for patients with type 2 diabetes, but it has not been clear if clinical benefits would outweigh costs for use as first-line therapies.

“Although clinical trials have demonstrated the clinical effectiveness of these newer drugs, they are hundreds of times more expensive than other ... diabetes drugs,” the researchers note.

On the other hand, costs may fall in the coming years when these new drugs come off-patent.

The current study was designed to help inform future clinical guidelines.

The researchers created a population simulation model based on the United Kingdom Prospective Diabetes Study, Outcomes Model version 2 (UKPDS OM2) for diabetes-related complications and mortality, with added information about hypoglycemic events, quality of life, and U.S. costs. 

The researchers also identified a nationally representative sample of people who would be eligible to start first-line diabetes therapy when their A1c reached 7% for the model. 

Using National Health and Nutrition Examination Survey (NHANES) data (2013-2016), the researchers identified about 7.3 million U.S. adults aged 18 and older with self-reported diabetes or an A1c greater than 6.5% with no reported use of diabetes medications.

Patients were an average age of 55, and 55% were women. They had had diabetes for an average of 4.2 years, and 36% had a history of diabetes complications.

The model projected that patients would have an improved life expectancy of 3.0 and 3.4 months from first-line SGLT2 inhibitors and GLP-1 agonists, respectively, compared with initial therapy with metformin due to reduced rates of macrovascular disease.  

“However, the current drug costs would be too high to encourage their adoption as first-line for usual clinical practice,” the researchers report.
 

‘Disparities could remain for decades’

Generic SGLT2 inhibitors could enter the marketplace shortly, because one of two dapagliflozin patents expired in October 2020 and approval for generic alternatives has been sought from the U.S. Food and Drug Administration, Dr. Choi and colleagues note.

However, it could still take decades for medication prices to drop low enough to become affordable, the group cautions. For example, a generic GLP-1 agonist became available in 2017, but costs remain high.

“Without external incentives,” the group writes, “limited access to these drug classes will likely persist (for example, due to higher copays or requirements for prior authorizations), as will further diabetes disparities – for decades into the future – because of differential access to care due to insurance (for example, private vs. public), which often tracks race and ethnicity.”

The study was supported by the American Diabetes Association. Dr. Choi was supported by a National Institutes of Health, National Institute on Aging grant. Dr. Laiteerapong and other co-authors are members of the National Institute of Diabetes and Digestive and Kidney Diseases Chicago Center for Diabetes Translation Research at the University of Chicago. Dr. Choi and Dr. Laiteerapong have reported no relevant financial relationships.

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