MDedge Infectious Disease

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Imran Ali, MD, is not due for recertification in internal medicine for a few more years, but he already plans to forego the traditional 1-day exam and opt instead for a newer one, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).

Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.

“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.

Many other internists contend the MOC is too time-consuming and expensive and have taken action.

Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.

One and Done, or More Flexibility?

Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.

The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.

Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.

Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.

“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.

In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.

The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.

The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.

Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.

She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.

An Unnecessary Exercise

As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.

According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.

Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”

The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.

“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.

Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.

Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.

Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.

“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.

The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.

Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.

Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.

“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”

A version of this article appeared on Medscape.com.

Imran Ali, MD, is not due for recertification in internal medicine for a few more years, but he already plans to forego the traditional 1-day exam and opt instead for a newer one, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).

Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.

“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.

Many other internists contend the MOC is too time-consuming and expensive and have taken action.

Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.

One and Done, or More Flexibility?

Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.

The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.

Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.

Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.

“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.

In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.

The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.

The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.

Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.

She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.

An Unnecessary Exercise

As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.

According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.

Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”

The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.

“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.

Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.

Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.

Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.

“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.

The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.

Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.

Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.

“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”

A version of this article appeared on Medscape.com.

Imran Ali, MD, is not due for recertification in internal medicine for a few more years, but he already plans to forego the traditional 1-day exam and opt instead for a newer one, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).

Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.

“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.

Many other internists contend the MOC is too time-consuming and expensive and have taken action.

Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.

One and Done, or More Flexibility?

Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.

The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.

Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.

Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.

“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.

In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.

The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.

The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.

Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.

She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.

An Unnecessary Exercise

As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.

According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.

Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”

The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.

“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.

Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.

Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.

Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.

“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.

The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.

Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.

Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.

“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.