CHEST Physician

Approximately 1 in 20 adults with outpatient respiratory syncytial virus (RSV) infections were readmitted to the hospital within 28 days, based on new data from more than 67,000 cases.

RSV remains a top cause of acute respiratory tract infections among adults in the United States, with an estimated 159,000 hospitalizations in those aged 65 years or older, wrote Suzanne N. Landi, MPH, PhD, of Pfizer in New York City, and colleagues in a study published in JAMA Network Open.

“Currently, limited estimates exist to determine the risk of hospitalization following outpatient RSV disease diagnoses in the United States,” said corresponding author Joshua T. Swan, PharmD, MPH, in an interview.

The current study was conducted to inform development of clinical trials, said Swan, senior director and category clinician in internal medicine and disease development at Pfizer, the sponsor of the study. These trials would assess the efficacy of an outpatient RSV antiviral treatment in preventing RSV-related hospitalization within 28 days among adults at a high risk for progression to severe illness, he said.

The authors reviewed data from 67,239 adults aged 18 years or older with medically attended RSV infections between October 1, 2016, and September 30, 2022. The data came from three databases: Optum (2771 patients), TriNetX (7442 patients), and Veradigm Network Electronic Health Record (VNEHR; 57,026 patients).

The primary outcome was all-cause hospitalization within 28 days of medically attended RSV.

Overall, the proportions of patients hospitalized within 28 days of infection were 6.2%, 6.0%, and 4.5% in Optum, TriNetX, and VNEHR databases, respectively.

Approximately two thirds of the patients (62%-67% across the three databases) were women, and 14.0%-54.5% were aged 65 years or older. The researchers also identified comorbidity prevalences of 20.0%-30.5% for chronic obstructive pulmonary disease (COPD), 14.6%-24.4% for heart failure (HF), and 14.6%-24.4% for asthma.

A majority of the patients (ranging from 74.5% to 90.6% across the three databases) fell into a high-risk subgroup, defined as age 65 years or older with asthma, COPD, and HF. In this high-risk group, the proportions of hospitalizations were 7.6%, 8.5%, and 6.5% for Optum, TriNetX, and VNEHR, respectively.

The findings were limited by several factors, including the use only of data from outpatient settings, which cannot be used to estimate the RSV burden in the general population, and the reliance only on diagnosis or procedure codes to identify comorbidities, the researchers noted.

However, “the absolute risk of hospitalization of 1 out of 20 patients observed in our study represents significant and meaningful risk for vulnerable adults, in a disease where much of the public’s attention has historically focused on risk of hospitalization for young children,” Swan said. “These results highlight the unmet medical need for outpatient interventions and preventive measures that can reduce hospitalizations.” 

 

Don’t Underestimate RSV Impact

The current study highlights the fact that RSV is a major cause of respiratory viral illness, said David R. Manoff, MD, associate professor of clinical thoracic medicine and surgery at Temple University, Philadelphia, in an interview.

“Historically, influenza, and, more recently, COVID-19 infection have generally been thought of as more likely to cause harm and, thus, have been more emphasized in terms of both vaccination and treatment,” said Manoff, who was not involved in the study.

The current study provides new evidence that infection with RSV can be far more serious than often recognized and a major potential source of both hospitalization and morbidity, Manoff said. In fact, data published in Morbidity and Mortality Weekly Report in 2023 showed that the risks of needing oxygen, intensive care unit (ICU) admission, intubation, and death were actually higher in patients hospitalized with RSV infections than in those hospitalized with influenza or COVID-19. “

Understanding which population is hospitalized in the first place is vital to targeting prevention measures,” he added.

The new data are consistent with previous studies showing that most patients with RSV infection have primarily upper respiratory tract infection–type symptoms, but that a minority will develop lower respiratory tract disease, Manoff noted.

The findings add to the argument for implementation of RSV vaccination, especially in high-risk individuals, and support the need for RSV testing when patients present for care, he said.

However, more research is needed to reflect recent numbers, Manoff said. The study timeframe of 2016-2022 not only precedes commercially available RSV vaccines but also includes the period of increased isolation and masking seen during the COVID-19 pandemic years of 2020-2021. “We need to see if the same trends continue in the post-pandemic era.” 

Additionally, the studies leading to approval of the RSV vaccine showed a reduction in hospitalization with RSV, and it is important to see how this reduction translates in real-world data and whether the RSV vaccines are reducing need for ICU admission, intubation, and death, Manoff said.

The study was funded by Pfizer, and Swan is a Pfizer employee. Manoff had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Approximately 1 in 20 adults with outpatient respiratory syncytial virus (RSV) infections were readmitted to the hospital within 28 days, based on new data from more than 67,000 cases.

RSV remains a top cause of acute respiratory tract infections among adults in the United States, with an estimated 159,000 hospitalizations in those aged 65 years or older, wrote Suzanne N. Landi, MPH, PhD, of Pfizer in New York City, and colleagues in a study published in JAMA Network Open.

“Currently, limited estimates exist to determine the risk of hospitalization following outpatient RSV disease diagnoses in the United States,” said corresponding author Joshua T. Swan, PharmD, MPH, in an interview.

The current study was conducted to inform development of clinical trials, said Swan, senior director and category clinician in internal medicine and disease development at Pfizer, the sponsor of the study. These trials would assess the efficacy of an outpatient RSV antiviral treatment in preventing RSV-related hospitalization within 28 days among adults at a high risk for progression to severe illness, he said.

The authors reviewed data from 67,239 adults aged 18 years or older with medically attended RSV infections between October 1, 2016, and September 30, 2022. The data came from three databases: Optum (2771 patients), TriNetX (7442 patients), and Veradigm Network Electronic Health Record (VNEHR; 57,026 patients).

The primary outcome was all-cause hospitalization within 28 days of medically attended RSV.

Overall, the proportions of patients hospitalized within 28 days of infection were 6.2%, 6.0%, and 4.5% in Optum, TriNetX, and VNEHR databases, respectively.

Approximately two thirds of the patients (62%-67% across the three databases) were women, and 14.0%-54.5% were aged 65 years or older. The researchers also identified comorbidity prevalences of 20.0%-30.5% for chronic obstructive pulmonary disease (COPD), 14.6%-24.4% for heart failure (HF), and 14.6%-24.4% for asthma.

A majority of the patients (ranging from 74.5% to 90.6% across the three databases) fell into a high-risk subgroup, defined as age 65 years or older with asthma, COPD, and HF. In this high-risk group, the proportions of hospitalizations were 7.6%, 8.5%, and 6.5% for Optum, TriNetX, and VNEHR, respectively.

The findings were limited by several factors, including the use only of data from outpatient settings, which cannot be used to estimate the RSV burden in the general population, and the reliance only on diagnosis or procedure codes to identify comorbidities, the researchers noted.

However, “the absolute risk of hospitalization of 1 out of 20 patients observed in our study represents significant and meaningful risk for vulnerable adults, in a disease where much of the public’s attention has historically focused on risk of hospitalization for young children,” Swan said. “These results highlight the unmet medical need for outpatient interventions and preventive measures that can reduce hospitalizations.” 

 

Don’t Underestimate RSV Impact

The current study highlights the fact that RSV is a major cause of respiratory viral illness, said David R. Manoff, MD, associate professor of clinical thoracic medicine and surgery at Temple University, Philadelphia, in an interview.

“Historically, influenza, and, more recently, COVID-19 infection have generally been thought of as more likely to cause harm and, thus, have been more emphasized in terms of both vaccination and treatment,” said Manoff, who was not involved in the study.

The current study provides new evidence that infection with RSV can be far more serious than often recognized and a major potential source of both hospitalization and morbidity, Manoff said. In fact, data published in Morbidity and Mortality Weekly Report in 2023 showed that the risks of needing oxygen, intensive care unit (ICU) admission, intubation, and death were actually higher in patients hospitalized with RSV infections than in those hospitalized with influenza or COVID-19. “

Understanding which population is hospitalized in the first place is vital to targeting prevention measures,” he added.

The new data are consistent with previous studies showing that most patients with RSV infection have primarily upper respiratory tract infection–type symptoms, but that a minority will develop lower respiratory tract disease, Manoff noted.

The findings add to the argument for implementation of RSV vaccination, especially in high-risk individuals, and support the need for RSV testing when patients present for care, he said.

However, more research is needed to reflect recent numbers, Manoff said. The study timeframe of 2016-2022 not only precedes commercially available RSV vaccines but also includes the period of increased isolation and masking seen during the COVID-19 pandemic years of 2020-2021. “We need to see if the same trends continue in the post-pandemic era.” 

Additionally, the studies leading to approval of the RSV vaccine showed a reduction in hospitalization with RSV, and it is important to see how this reduction translates in real-world data and whether the RSV vaccines are reducing need for ICU admission, intubation, and death, Manoff said.

The study was funded by Pfizer, and Swan is a Pfizer employee. Manoff had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Approximately 1 in 20 adults with outpatient respiratory syncytial virus (RSV) infections were readmitted to the hospital within 28 days, based on new data from more than 67,000 cases.

RSV remains a top cause of acute respiratory tract infections among adults in the United States, with an estimated 159,000 hospitalizations in those aged 65 years or older, wrote Suzanne N. Landi, MPH, PhD, of Pfizer in New York City, and colleagues in a study published in JAMA Network Open.

“Currently, limited estimates exist to determine the risk of hospitalization following outpatient RSV disease diagnoses in the United States,” said corresponding author Joshua T. Swan, PharmD, MPH, in an interview.

The current study was conducted to inform development of clinical trials, said Swan, senior director and category clinician in internal medicine and disease development at Pfizer, the sponsor of the study. These trials would assess the efficacy of an outpatient RSV antiviral treatment in preventing RSV-related hospitalization within 28 days among adults at a high risk for progression to severe illness, he said.

The authors reviewed data from 67,239 adults aged 18 years or older with medically attended RSV infections between October 1, 2016, and September 30, 2022. The data came from three databases: Optum (2771 patients), TriNetX (7442 patients), and Veradigm Network Electronic Health Record (VNEHR; 57,026 patients).

The primary outcome was all-cause hospitalization within 28 days of medically attended RSV.

Overall, the proportions of patients hospitalized within 28 days of infection were 6.2%, 6.0%, and 4.5% in Optum, TriNetX, and VNEHR databases, respectively.

Approximately two thirds of the patients (62%-67% across the three databases) were women, and 14.0%-54.5% were aged 65 years or older. The researchers also identified comorbidity prevalences of 20.0%-30.5% for chronic obstructive pulmonary disease (COPD), 14.6%-24.4% for heart failure (HF), and 14.6%-24.4% for asthma.

A majority of the patients (ranging from 74.5% to 90.6% across the three databases) fell into a high-risk subgroup, defined as age 65 years or older with asthma, COPD, and HF. In this high-risk group, the proportions of hospitalizations were 7.6%, 8.5%, and 6.5% for Optum, TriNetX, and VNEHR, respectively.

The findings were limited by several factors, including the use only of data from outpatient settings, which cannot be used to estimate the RSV burden in the general population, and the reliance only on diagnosis or procedure codes to identify comorbidities, the researchers noted.

However, “the absolute risk of hospitalization of 1 out of 20 patients observed in our study represents significant and meaningful risk for vulnerable adults, in a disease where much of the public’s attention has historically focused on risk of hospitalization for young children,” Swan said. “These results highlight the unmet medical need for outpatient interventions and preventive measures that can reduce hospitalizations.” 

 

Don’t Underestimate RSV Impact

The current study highlights the fact that RSV is a major cause of respiratory viral illness, said David R. Manoff, MD, associate professor of clinical thoracic medicine and surgery at Temple University, Philadelphia, in an interview.

“Historically, influenza, and, more recently, COVID-19 infection have generally been thought of as more likely to cause harm and, thus, have been more emphasized in terms of both vaccination and treatment,” said Manoff, who was not involved in the study.

The current study provides new evidence that infection with RSV can be far more serious than often recognized and a major potential source of both hospitalization and morbidity, Manoff said. In fact, data published in Morbidity and Mortality Weekly Report in 2023 showed that the risks of needing oxygen, intensive care unit (ICU) admission, intubation, and death were actually higher in patients hospitalized with RSV infections than in those hospitalized with influenza or COVID-19. “

Understanding which population is hospitalized in the first place is vital to targeting prevention measures,” he added.

The new data are consistent with previous studies showing that most patients with RSV infection have primarily upper respiratory tract infection–type symptoms, but that a minority will develop lower respiratory tract disease, Manoff noted.

The findings add to the argument for implementation of RSV vaccination, especially in high-risk individuals, and support the need for RSV testing when patients present for care, he said.

However, more research is needed to reflect recent numbers, Manoff said. The study timeframe of 2016-2022 not only precedes commercially available RSV vaccines but also includes the period of increased isolation and masking seen during the COVID-19 pandemic years of 2020-2021. “We need to see if the same trends continue in the post-pandemic era.” 

Additionally, the studies leading to approval of the RSV vaccine showed a reduction in hospitalization with RSV, and it is important to see how this reduction translates in real-world data and whether the RSV vaccines are reducing need for ICU admission, intubation, and death, Manoff said.

The study was funded by Pfizer, and Swan is a Pfizer employee. Manoff had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

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Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.

Key Takeaways:

• Many physicians struggle to identify burnout due to stigma and self-blame.
• Awareness of burnout symptoms is essential for early intervention and healthy coping.
• Seeking support can prevent burnout from worsening and improve quality of life.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.

Key Takeaways:

• Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
• Practicing self-compassion can improve long-term resilience and prevent burnout.
• The changing landscape of healthcare supports a more balanced approach to physician well-being.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations. 

Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

Summary and Key Highlights

Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.

Key Takeaways:

• Relying solely on external validation can deepen burnout and affect well-being.
• Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
• Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.

Our Editors Also Recommend: 

Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’

Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance 

Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance 

A Transformative Rx for Burnout, Grief, and Illness: Dance 

 

Next Medscape Masters Event:

Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.

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

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created 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.

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created 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.

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created 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.

Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.

Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.

“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.

We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead. 

 

You Won’t Know Everything, and That’s Okay

When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.

“No one expects you to know it all,” she explained. “What’s important is to cultivate curiosity and a willingness to ask for help when needed.” 

David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”

Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.

 

You’ll Take Your Work Home With You

Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan. 

“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”

When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”

Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home. 

“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”

 

Burnout Is Real — Make Self-Care a Priority 

As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said. 

The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”

That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”

 

Avoid Relying Too Heavily on Tech

Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”

It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.

“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.

 

Partner With Your Patients, Even When It’s Difficult

Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.

“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”

Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”

Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”

At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.

“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”

 

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

Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.

Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.

“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.

We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead. 

 

You Won’t Know Everything, and That’s Okay

When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.

“No one expects you to know it all,” she explained. “What’s important is to cultivate curiosity and a willingness to ask for help when needed.” 

David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”

Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.

 

You’ll Take Your Work Home With You

Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan. 

“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”

When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”

Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home. 

“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”

 

Burnout Is Real — Make Self-Care a Priority 

As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said. 

The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”

That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”

 

Avoid Relying Too Heavily on Tech

Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”

It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.

“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.

 

Partner With Your Patients, Even When It’s Difficult

Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.

“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”

Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”

Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”

At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.

“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”

 

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

Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.

Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.

“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.

We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead. 

 

You Won’t Know Everything, and That’s Okay

When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.

“No one expects you to know it all,” she explained. “What’s important is to cultivate curiosity and a willingness to ask for help when needed.” 

David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”

Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.

 

You’ll Take Your Work Home With You

Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan. 

“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”

When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”

Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home. 

“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”

 

Burnout Is Real — Make Self-Care a Priority 

As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said. 

The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”

That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”

 

Avoid Relying Too Heavily on Tech

Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”

It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.

“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.

 

Partner With Your Patients, Even When It’s Difficult

Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.

“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”

Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”

Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”

At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.

“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”

 

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

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

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

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

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

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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