Federal Practitioner

Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.

Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.

However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.

In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.

The primary outcome was the time from the date of a diagnosis or first treatment of a severe physical health condition to a death by suicide. The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.

The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.

The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.

For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.

The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.

The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.

The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.

The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.

“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.

However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.

The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.

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

Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.

Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.

However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.

In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.

The primary outcome was the time from the date of a diagnosis or first treatment of a severe physical health condition to a death by suicide. The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.

The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.

The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.

For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.

The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.

The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.

The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.

The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.

“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.

However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.

The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.

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

Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.

Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.

However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.

In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.

The primary outcome was the time from the date of a diagnosis or first treatment of a severe physical health condition to a death by suicide. The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.

The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.

The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.

For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.

The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.

The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.

The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.

The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.

“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.

However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.

The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.

“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”

Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.

“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”

According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.

For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.

Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).

Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.

Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.

Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”

In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”

Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”

As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”

The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.

In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.

“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”

The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”

The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.

A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.

“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”

Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.

“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”

According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.

For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.

Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).

Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.

Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.

Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”

In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”

Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”

As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”

The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.

In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.

“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”

The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”

The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.

A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.

“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”

Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.

“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”

According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.

For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.

Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).

Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.

Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.

Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”

In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”

Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”

As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”

The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.

In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.

“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”

The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”

The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.

In 2020, the rapid spread of the newly identified SARS-CoV-2 coronavirus led various global public health institutions to establish strategies to stop transmission and reduce mortality. Nonpharmacological measures – including social distancing, regular hand washing, and the use of face masks – contributed to reducing the impact of the COVID-19 pandemic on health systems in different regions of the world. However, because of the implementation of these measures, the transmission of other infectious agents also experienced a marked reduction.

Approximately 3 years after the start of the pandemic, it is evident that SARS-COV-2 has also affected the dynamic of other infectious agents, generating phenomena ranging from an immunity gap, which favors the increase in some diseases, to the apparent disappearance of an influenza virus lineage.
 

Understanding the phenomenon

In mid-2021, doctors and researchers around the world began to share their opinions about the side effect of the strict measures implemented to contain COVID-19.

In May 2021, along with some coresearchers, Emmanuel Grimprel, MD, of the Pediatric Infectious Pathology Group in Créteil, France, wrote for Infectious Disease Now, “The transmission of some pathogens is often similar to that of SARS-CoV-2, essentially large droplets, aerosols, and direct hand contact, often with lower transmissibility. The lack of immune system stimulation due to nonpharmaceutical measures induces an ‘immune debt’ that may have negative consequences when the pandemic is under control.” According to the authors, mathematical models evaluated up to that point were already suggesting that the respiratory syncytial virus (RSV) and influenza A epidemics would be more serious in subsequent years.

In July 2022, a commentary in The Lancet led by Kevin Messacar, MD, of the University of Colorado at Denver, Aurora, grew in relevance and gave prominence to the phenomenon. In the commentary, Dr. Messacar and a group of experts explained how the decrease in exposure to endemic viruses had given rise to an immunity gap.

“The immunity gap phenomenon that has been reported in articles such as The Lancet publication is mainly due to the isolation that took place to prevent SARS-CoV-2 infections. Although this distancing was a good response to combat infections, or at least delay them while coronavirus research advanced, what we are now experiencing is the increase in cases of respiratory diseases caused by other agents such as respiratory syncytial virus and influenza due to lack of exposure,” as explained to this news organization by Erandeni Martínez Jiménez, biomedicine graduate and member of the Medical Virology Laboratory of the Mexican Institute of Social Security, at the Zone No. 5 General Hospital in Metepec-Atlixco, Mexico.

“This phenomenon occurs in all age groups. However, it is more evident in children and babies, since at their age, they have been exposed to fewer pathogens and, when added to isolation, makes this immunity gap more evident. Many immunologists compare this to hygiene theory in which it is explained that a ‘sterile’ environment will cause children to avoid the everyday and common pathogens required to be able to develop an adequate immune system,” added Martínez Jimenez.

“In addition, due to the isolation, the vaccination rate in children decreased, since many parents did not risk their children going out. This causes the immunity gap to grow even further as these children are not protected against common pathogens. While a mother passes antibodies to the child through the uterus via her placenta, the mother will only pass on those antibodies to which she has been exposed and as expected due to the lockdown, exposure to other pathogens has been greatly reduced.”

On the other hand, Andreu Comas, MD, PhD, MHS, of the Center for Research in Health Sciences and Biomedicine of the Autonomous University of San Luis Potosí (Mexico), considered that there are other immunity gaps that are not limited to respiratory infections and that are related to the fall in vaccination coverage. “Children are going to experience several immunity gaps. In the middle of the previous 6-year term, we had a vaccination schedule coverage of around 70% for children. Now that vaccination coverage has fallen to 30%, today we have an immunity gap for measles, rubella, mumps, tetanus, diphtheria, whooping cough, and meningeal tuberculosis. We have a significant growth or risk for other diseases.”
 

Lineage extinction

Three types of influenza viruses – A, B, and C – cause infections in humans. Although influenza A virus is the main type associated with infections during seasonal periods, as of 2020, influenza B virus was considered the causative agent of about a quarter of annual influenza cases.

During the onset of the COVID-19 pandemic, cocirculation of the two distinct lineages of influenza B viruses, B/Victoria/2/1987 (B/Victoria) and B/Yamagata/16/1988 (B/Yamagata), decreased significantly. According to data from the FluNet tool, which is coordinated by the World Health Organization, since March 2020 the isolation or sequencing of viruses belonging to the Yamagata lineage was not conclusively carried out.

Specialists like John Paget, PhD, from the Netherlands Institute for Health Services Research (Nivel) in Utrecht, have indicated that determining the extinction of the B/Yamagata lineage is critical. There is the possibility of a reintroduction of the lineage, as has occurred in the past with the reemergence of influenza A (H1N1) in 1997, which could represent a risk in subsequent years.

“In the next few years, research related to viruses such as influenza B and the impact on population immunity will be important. Let’s remember that influenza changes every year due to its characteristics, so a lack of exposure will also have an impact on the development of the disease,” said Martínez Jiménez.
 

Vaccination is essential

According to Dr. Comas, the only way to overcome the immunity gap phenomenon is through vaccination campaigns. “There is no other way to overcome the phenomenon, and how fast it is done will depend on the effort,” he said.

“In the case of COVID-19, it is not planned to vaccinate children under 5 years of age, and if we do not vaccinate children under 5 years of age, that gap will exist. In addition, this winter season will be important to know whether we are already endemic or not. It will be the key point, and it will determine if we will have a peak or not in the summer.

“In the case of the rest of the diseases, we need to correct what has been deficient in different governments, and we are going to have the resurgence of other infectious diseases that had already been forgotten. We have the example of poliomyelitis, the increase in meningeal tuberculosis, and we will have an increase in whooping cough and pertussislike syndrome. In this sense, we are going back to the point where Mexico and the world were around the ‘60s and ‘70s, and we have to be very alert to detect, isolate, and revaccinate.”

Finally, Dr. Comas called for continuing precautionary measures before the arrival of the sixth wave. “At a national level, the sixth wave of COVID-19 has already begun, and an increase in cases is expected in January. Regarding vaccines, if you are over 18 years of age and have not had any vaccine dose, you can get Abdala, however, there are no studies on this vaccine as a booster, and it is not authorized by the Mexican government for this purpose. Therefore, it is necessary to continue with measures such as the use of face masks in crowded places or with poor ventilation, and in the event of having symptoms, avoid going out and encourage ventilation at work and schools. If we do this, at least in the case of diseases that are transmitted by the respiratory route, the impact will be minimal.”

Martínez Jiménez and Dr. Comas have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish Edition.

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

In 2020, the rapid spread of the newly identified SARS-CoV-2 coronavirus led various global public health institutions to establish strategies to stop transmission and reduce mortality. Nonpharmacological measures – including social distancing, regular hand washing, and the use of face masks – contributed to reducing the impact of the COVID-19 pandemic on health systems in different regions of the world. However, because of the implementation of these measures, the transmission of other infectious agents also experienced a marked reduction.

Approximately 3 years after the start of the pandemic, it is evident that SARS-COV-2 has also affected the dynamic of other infectious agents, generating phenomena ranging from an immunity gap, which favors the increase in some diseases, to the apparent disappearance of an influenza virus lineage.
 

Understanding the phenomenon

In mid-2021, doctors and researchers around the world began to share their opinions about the side effect of the strict measures implemented to contain COVID-19.

In May 2021, along with some coresearchers, Emmanuel Grimprel, MD, of the Pediatric Infectious Pathology Group in Créteil, France, wrote for Infectious Disease Now, “The transmission of some pathogens is often similar to that of SARS-CoV-2, essentially large droplets, aerosols, and direct hand contact, often with lower transmissibility. The lack of immune system stimulation due to nonpharmaceutical measures induces an ‘immune debt’ that may have negative consequences when the pandemic is under control.” According to the authors, mathematical models evaluated up to that point were already suggesting that the respiratory syncytial virus (RSV) and influenza A epidemics would be more serious in subsequent years.

In July 2022, a commentary in The Lancet led by Kevin Messacar, MD, of the University of Colorado at Denver, Aurora, grew in relevance and gave prominence to the phenomenon. In the commentary, Dr. Messacar and a group of experts explained how the decrease in exposure to endemic viruses had given rise to an immunity gap.

“The immunity gap phenomenon that has been reported in articles such as The Lancet publication is mainly due to the isolation that took place to prevent SARS-CoV-2 infections. Although this distancing was a good response to combat infections, or at least delay them while coronavirus research advanced, what we are now experiencing is the increase in cases of respiratory diseases caused by other agents such as respiratory syncytial virus and influenza due to lack of exposure,” as explained to this news organization by Erandeni Martínez Jiménez, biomedicine graduate and member of the Medical Virology Laboratory of the Mexican Institute of Social Security, at the Zone No. 5 General Hospital in Metepec-Atlixco, Mexico.

“This phenomenon occurs in all age groups. However, it is more evident in children and babies, since at their age, they have been exposed to fewer pathogens and, when added to isolation, makes this immunity gap more evident. Many immunologists compare this to hygiene theory in which it is explained that a ‘sterile’ environment will cause children to avoid the everyday and common pathogens required to be able to develop an adequate immune system,” added Martínez Jimenez.

“In addition, due to the isolation, the vaccination rate in children decreased, since many parents did not risk their children going out. This causes the immunity gap to grow even further as these children are not protected against common pathogens. While a mother passes antibodies to the child through the uterus via her placenta, the mother will only pass on those antibodies to which she has been exposed and as expected due to the lockdown, exposure to other pathogens has been greatly reduced.”

On the other hand, Andreu Comas, MD, PhD, MHS, of the Center for Research in Health Sciences and Biomedicine of the Autonomous University of San Luis Potosí (Mexico), considered that there are other immunity gaps that are not limited to respiratory infections and that are related to the fall in vaccination coverage. “Children are going to experience several immunity gaps. In the middle of the previous 6-year term, we had a vaccination schedule coverage of around 70% for children. Now that vaccination coverage has fallen to 30%, today we have an immunity gap for measles, rubella, mumps, tetanus, diphtheria, whooping cough, and meningeal tuberculosis. We have a significant growth or risk for other diseases.”
 

Lineage extinction

Three types of influenza viruses – A, B, and C – cause infections in humans. Although influenza A virus is the main type associated with infections during seasonal periods, as of 2020, influenza B virus was considered the causative agent of about a quarter of annual influenza cases.

During the onset of the COVID-19 pandemic, cocirculation of the two distinct lineages of influenza B viruses, B/Victoria/2/1987 (B/Victoria) and B/Yamagata/16/1988 (B/Yamagata), decreased significantly. According to data from the FluNet tool, which is coordinated by the World Health Organization, since March 2020 the isolation or sequencing of viruses belonging to the Yamagata lineage was not conclusively carried out.

Specialists like John Paget, PhD, from the Netherlands Institute for Health Services Research (Nivel) in Utrecht, have indicated that determining the extinction of the B/Yamagata lineage is critical. There is the possibility of a reintroduction of the lineage, as has occurred in the past with the reemergence of influenza A (H1N1) in 1997, which could represent a risk in subsequent years.

“In the next few years, research related to viruses such as influenza B and the impact on population immunity will be important. Let’s remember that influenza changes every year due to its characteristics, so a lack of exposure will also have an impact on the development of the disease,” said Martínez Jiménez.
 

Vaccination is essential

According to Dr. Comas, the only way to overcome the immunity gap phenomenon is through vaccination campaigns. “There is no other way to overcome the phenomenon, and how fast it is done will depend on the effort,” he said.

“In the case of COVID-19, it is not planned to vaccinate children under 5 years of age, and if we do not vaccinate children under 5 years of age, that gap will exist. In addition, this winter season will be important to know whether we are already endemic or not. It will be the key point, and it will determine if we will have a peak or not in the summer.

“In the case of the rest of the diseases, we need to correct what has been deficient in different governments, and we are going to have the resurgence of other infectious diseases that had already been forgotten. We have the example of poliomyelitis, the increase in meningeal tuberculosis, and we will have an increase in whooping cough and pertussislike syndrome. In this sense, we are going back to the point where Mexico and the world were around the ‘60s and ‘70s, and we have to be very alert to detect, isolate, and revaccinate.”

Finally, Dr. Comas called for continuing precautionary measures before the arrival of the sixth wave. “At a national level, the sixth wave of COVID-19 has already begun, and an increase in cases is expected in January. Regarding vaccines, if you are over 18 years of age and have not had any vaccine dose, you can get Abdala, however, there are no studies on this vaccine as a booster, and it is not authorized by the Mexican government for this purpose. Therefore, it is necessary to continue with measures such as the use of face masks in crowded places or with poor ventilation, and in the event of having symptoms, avoid going out and encourage ventilation at work and schools. If we do this, at least in the case of diseases that are transmitted by the respiratory route, the impact will be minimal.”

Martínez Jiménez and Dr. Comas have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish Edition.

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

In 2020, the rapid spread of the newly identified SARS-CoV-2 coronavirus led various global public health institutions to establish strategies to stop transmission and reduce mortality. Nonpharmacological measures – including social distancing, regular hand washing, and the use of face masks – contributed to reducing the impact of the COVID-19 pandemic on health systems in different regions of the world. However, because of the implementation of these measures, the transmission of other infectious agents also experienced a marked reduction.

Approximately 3 years after the start of the pandemic, it is evident that SARS-COV-2 has also affected the dynamic of other infectious agents, generating phenomena ranging from an immunity gap, which favors the increase in some diseases, to the apparent disappearance of an influenza virus lineage.
 

Understanding the phenomenon

In mid-2021, doctors and researchers around the world began to share their opinions about the side effect of the strict measures implemented to contain COVID-19.

In May 2021, along with some coresearchers, Emmanuel Grimprel, MD, of the Pediatric Infectious Pathology Group in Créteil, France, wrote for Infectious Disease Now, “The transmission of some pathogens is often similar to that of SARS-CoV-2, essentially large droplets, aerosols, and direct hand contact, often with lower transmissibility. The lack of immune system stimulation due to nonpharmaceutical measures induces an ‘immune debt’ that may have negative consequences when the pandemic is under control.” According to the authors, mathematical models evaluated up to that point were already suggesting that the respiratory syncytial virus (RSV) and influenza A epidemics would be more serious in subsequent years.

In July 2022, a commentary in The Lancet led by Kevin Messacar, MD, of the University of Colorado at Denver, Aurora, grew in relevance and gave prominence to the phenomenon. In the commentary, Dr. Messacar and a group of experts explained how the decrease in exposure to endemic viruses had given rise to an immunity gap.

“The immunity gap phenomenon that has been reported in articles such as The Lancet publication is mainly due to the isolation that took place to prevent SARS-CoV-2 infections. Although this distancing was a good response to combat infections, or at least delay them while coronavirus research advanced, what we are now experiencing is the increase in cases of respiratory diseases caused by other agents such as respiratory syncytial virus and influenza due to lack of exposure,” as explained to this news organization by Erandeni Martínez Jiménez, biomedicine graduate and member of the Medical Virology Laboratory of the Mexican Institute of Social Security, at the Zone No. 5 General Hospital in Metepec-Atlixco, Mexico.

“This phenomenon occurs in all age groups. However, it is more evident in children and babies, since at their age, they have been exposed to fewer pathogens and, when added to isolation, makes this immunity gap more evident. Many immunologists compare this to hygiene theory in which it is explained that a ‘sterile’ environment will cause children to avoid the everyday and common pathogens required to be able to develop an adequate immune system,” added Martínez Jimenez.

“In addition, due to the isolation, the vaccination rate in children decreased, since many parents did not risk their children going out. This causes the immunity gap to grow even further as these children are not protected against common pathogens. While a mother passes antibodies to the child through the uterus via her placenta, the mother will only pass on those antibodies to which she has been exposed and as expected due to the lockdown, exposure to other pathogens has been greatly reduced.”

On the other hand, Andreu Comas, MD, PhD, MHS, of the Center for Research in Health Sciences and Biomedicine of the Autonomous University of San Luis Potosí (Mexico), considered that there are other immunity gaps that are not limited to respiratory infections and that are related to the fall in vaccination coverage. “Children are going to experience several immunity gaps. In the middle of the previous 6-year term, we had a vaccination schedule coverage of around 70% for children. Now that vaccination coverage has fallen to 30%, today we have an immunity gap for measles, rubella, mumps, tetanus, diphtheria, whooping cough, and meningeal tuberculosis. We have a significant growth or risk for other diseases.”
 

Lineage extinction

Three types of influenza viruses – A, B, and C – cause infections in humans. Although influenza A virus is the main type associated with infections during seasonal periods, as of 2020, influenza B virus was considered the causative agent of about a quarter of annual influenza cases.

During the onset of the COVID-19 pandemic, cocirculation of the two distinct lineages of influenza B viruses, B/Victoria/2/1987 (B/Victoria) and B/Yamagata/16/1988 (B/Yamagata), decreased significantly. According to data from the FluNet tool, which is coordinated by the World Health Organization, since March 2020 the isolation or sequencing of viruses belonging to the Yamagata lineage was not conclusively carried out.

Specialists like John Paget, PhD, from the Netherlands Institute for Health Services Research (Nivel) in Utrecht, have indicated that determining the extinction of the B/Yamagata lineage is critical. There is the possibility of a reintroduction of the lineage, as has occurred in the past with the reemergence of influenza A (H1N1) in 1997, which could represent a risk in subsequent years.

“In the next few years, research related to viruses such as influenza B and the impact on population immunity will be important. Let’s remember that influenza changes every year due to its characteristics, so a lack of exposure will also have an impact on the development of the disease,” said Martínez Jiménez.
 

Vaccination is essential

According to Dr. Comas, the only way to overcome the immunity gap phenomenon is through vaccination campaigns. “There is no other way to overcome the phenomenon, and how fast it is done will depend on the effort,” he said.

“In the case of COVID-19, it is not planned to vaccinate children under 5 years of age, and if we do not vaccinate children under 5 years of age, that gap will exist. In addition, this winter season will be important to know whether we are already endemic or not. It will be the key point, and it will determine if we will have a peak or not in the summer.

“In the case of the rest of the diseases, we need to correct what has been deficient in different governments, and we are going to have the resurgence of other infectious diseases that had already been forgotten. We have the example of poliomyelitis, the increase in meningeal tuberculosis, and we will have an increase in whooping cough and pertussislike syndrome. In this sense, we are going back to the point where Mexico and the world were around the ‘60s and ‘70s, and we have to be very alert to detect, isolate, and revaccinate.”

Finally, Dr. Comas called for continuing precautionary measures before the arrival of the sixth wave. “At a national level, the sixth wave of COVID-19 has already begun, and an increase in cases is expected in January. Regarding vaccines, if you are over 18 years of age and have not had any vaccine dose, you can get Abdala, however, there are no studies on this vaccine as a booster, and it is not authorized by the Mexican government for this purpose. Therefore, it is necessary to continue with measures such as the use of face masks in crowded places or with poor ventilation, and in the event of having symptoms, avoid going out and encourage ventilation at work and schools. If we do this, at least in the case of diseases that are transmitted by the respiratory route, the impact will be minimal.”

Martínez Jiménez and Dr. Comas have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish Edition.

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

Exercise helps patients with knee osteoarthritis, but more isn’t necessarily better, new research shows.

A low-dose exercise regimen helped patients with knee OA about as much as a more intense workout plan, according to trial results published online in Annals of Internal Medicine.

kali9/Getty Images

Both high and low doses of exercise reduced pain and improved function and quality of life.

The improvements with the lower-dose plan and its 98% adherence rate are encouraging, said Nick Trasolini, MD, assistant professor of orthopedic surgery at Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, N.C.

“This is a very doable amount of medical exercise therapy for patients with knee osteoarthritis, and one that makes a big difference in patient-reported symptoms,” Dr. Trasolini, who was not involved in the study, said in an interview.
 

What’s the right dose?

Exercise is a go-to treatment for knee OA, but the precise dose to recommend has been unclear. To study this question, Tom Arild Torstensen, MSc, RPT, with Karolinska Institutet, Huddinge, Sweden, and Holten Institute, Stockholm, and colleagues conducted a trial at four centers in Sweden and Norway.

The study included 189 men and women with knee OA. Participants were randomly assigned to low- or high-dose exercise plans, which they performed three times per week for 12 weeks under the supervision of a physiotherapist.

Participants in the high-dose group performed 11 exercises during each session, which lasted 70-90 minutes.

The low-dose regimen consisted of five exercises – cycling, squats, step-ups, step-downs, and knee extensions – performed for 20–30 minutes.

The researchers measured outcomes using the Knee Injury and Osteoarthritis Outcome Score, which assesses pain, other symptoms, function in daily living, function in sports and recreation, and knee-related quality of life.

“Patients in both groups improved significantly over time, but high-dose exercise was not superior to low-dose exercise in most comparisons,” the study investigators reported

High-dose exercise was associated with better function in sports and recreational activity and knee-related quality of life at 6 months. Those differences did not persist at 1 year, however. The researchers reported no safety concerns with either intervention.

Adherence was “nearly perfect” in the low-dose group. It was slightly lower in the high-dose group, the researchers said.

“Interestingly, it seems that high-dose treatment could be preferable to low-dose treatment in the long run for people who lead active lives,” they wrote. “This should be the subject of future studies.”

All clinical practice guidelines for knee OA recommend exercise, but “we do not know the optimal dose,” Kim Bennell, PhD, a research physiotherapist at the University of Melbourne, said in an interview.

Dose has components, including number of times per week, number of exercises, sets and repetitions, intensity, and duration of exercise sessions, Dr. Bennell said.

“These results suggest that an exercise program that involves less time and fewer exercises can still offer benefits and may be easier for patients to undertake and stick at than one that involves greater time and effort,” she said.

The study was supported by the Swedish Rheumatic Fund. Dr. Trasolini and Dr. Bennell have disclosed no relevant financial relationships.

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

Exercise helps patients with knee osteoarthritis, but more isn’t necessarily better, new research shows.

A low-dose exercise regimen helped patients with knee OA about as much as a more intense workout plan, according to trial results published online in Annals of Internal Medicine.

kali9/Getty Images

Both high and low doses of exercise reduced pain and improved function and quality of life.

The improvements with the lower-dose plan and its 98% adherence rate are encouraging, said Nick Trasolini, MD, assistant professor of orthopedic surgery at Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, N.C.

“This is a very doable amount of medical exercise therapy for patients with knee osteoarthritis, and one that makes a big difference in patient-reported symptoms,” Dr. Trasolini, who was not involved in the study, said in an interview.
 

What’s the right dose?

Exercise is a go-to treatment for knee OA, but the precise dose to recommend has been unclear. To study this question, Tom Arild Torstensen, MSc, RPT, with Karolinska Institutet, Huddinge, Sweden, and Holten Institute, Stockholm, and colleagues conducted a trial at four centers in Sweden and Norway.

The study included 189 men and women with knee OA. Participants were randomly assigned to low- or high-dose exercise plans, which they performed three times per week for 12 weeks under the supervision of a physiotherapist.

Participants in the high-dose group performed 11 exercises during each session, which lasted 70-90 minutes.

The low-dose regimen consisted of five exercises – cycling, squats, step-ups, step-downs, and knee extensions – performed for 20–30 minutes.

The researchers measured outcomes using the Knee Injury and Osteoarthritis Outcome Score, which assesses pain, other symptoms, function in daily living, function in sports and recreation, and knee-related quality of life.

“Patients in both groups improved significantly over time, but high-dose exercise was not superior to low-dose exercise in most comparisons,” the study investigators reported

High-dose exercise was associated with better function in sports and recreational activity and knee-related quality of life at 6 months. Those differences did not persist at 1 year, however. The researchers reported no safety concerns with either intervention.

Adherence was “nearly perfect” in the low-dose group. It was slightly lower in the high-dose group, the researchers said.

“Interestingly, it seems that high-dose treatment could be preferable to low-dose treatment in the long run for people who lead active lives,” they wrote. “This should be the subject of future studies.”

All clinical practice guidelines for knee OA recommend exercise, but “we do not know the optimal dose,” Kim Bennell, PhD, a research physiotherapist at the University of Melbourne, said in an interview.

Dose has components, including number of times per week, number of exercises, sets and repetitions, intensity, and duration of exercise sessions, Dr. Bennell said.

“These results suggest that an exercise program that involves less time and fewer exercises can still offer benefits and may be easier for patients to undertake and stick at than one that involves greater time and effort,” she said.

The study was supported by the Swedish Rheumatic Fund. Dr. Trasolini and Dr. Bennell have disclosed no relevant financial relationships.

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

Exercise helps patients with knee osteoarthritis, but more isn’t necessarily better, new research shows.

A low-dose exercise regimen helped patients with knee OA about as much as a more intense workout plan, according to trial results published online in Annals of Internal Medicine.

kali9/Getty Images

Both high and low doses of exercise reduced pain and improved function and quality of life.

The improvements with the lower-dose plan and its 98% adherence rate are encouraging, said Nick Trasolini, MD, assistant professor of orthopedic surgery at Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, N.C.

“This is a very doable amount of medical exercise therapy for patients with knee osteoarthritis, and one that makes a big difference in patient-reported symptoms,” Dr. Trasolini, who was not involved in the study, said in an interview.
 

What’s the right dose?

Exercise is a go-to treatment for knee OA, but the precise dose to recommend has been unclear. To study this question, Tom Arild Torstensen, MSc, RPT, with Karolinska Institutet, Huddinge, Sweden, and Holten Institute, Stockholm, and colleagues conducted a trial at four centers in Sweden and Norway.

The study included 189 men and women with knee OA. Participants were randomly assigned to low- or high-dose exercise plans, which they performed three times per week for 12 weeks under the supervision of a physiotherapist.

Participants in the high-dose group performed 11 exercises during each session, which lasted 70-90 minutes.

The low-dose regimen consisted of five exercises – cycling, squats, step-ups, step-downs, and knee extensions – performed for 20–30 minutes.

The researchers measured outcomes using the Knee Injury and Osteoarthritis Outcome Score, which assesses pain, other symptoms, function in daily living, function in sports and recreation, and knee-related quality of life.

“Patients in both groups improved significantly over time, but high-dose exercise was not superior to low-dose exercise in most comparisons,” the study investigators reported

High-dose exercise was associated with better function in sports and recreational activity and knee-related quality of life at 6 months. Those differences did not persist at 1 year, however. The researchers reported no safety concerns with either intervention.

Adherence was “nearly perfect” in the low-dose group. It was slightly lower in the high-dose group, the researchers said.

“Interestingly, it seems that high-dose treatment could be preferable to low-dose treatment in the long run for people who lead active lives,” they wrote. “This should be the subject of future studies.”

All clinical practice guidelines for knee OA recommend exercise, but “we do not know the optimal dose,” Kim Bennell, PhD, a research physiotherapist at the University of Melbourne, said in an interview.

Dose has components, including number of times per week, number of exercises, sets and repetitions, intensity, and duration of exercise sessions, Dr. Bennell said.

“These results suggest that an exercise program that involves less time and fewer exercises can still offer benefits and may be easier for patients to undertake and stick at than one that involves greater time and effort,” she said.

The study was supported by the Swedish Rheumatic Fund. Dr. Trasolini and Dr. Bennell have disclosed no relevant financial relationships.

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

Current depression guidelines offer incomplete guidance for clinicians to identify antidepressant withdrawal, based on data from a review of 21 guidelines.

Previous research suggests that approximately half of patients who discontinue or decrease dosage of antidepressants experience withdrawal symptoms, wrote Anders Sørensen, MD, of Copenhagen University Hospital, and colleagues. These symptoms are diverse and may include flulike symptoms, fatigue, anxiety, and sensations of electric shock, they noted. Most withdrawal effects last for a few weeks, but some persist for months or years, sometimes described as persistent postwithdrawal disorder, they added.

“Symptoms of withdrawal and depression overlap considerably but constitute two fundamentally different clinical conditions, which makes it important to distinguish between the two,” the researchers emphasized.

In a study published in the Journal of Affective Disorders, the researchers identified 21 clinical practice guidelines (CPGs) for depression published between 1998 and 2022. The guidelines were published in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland, and New Zealand. They compared descriptions of withdrawal from antidepressants and calculated the proportion of CPGs with different information.

Overall, 15 of the 21 studies in the review (71%) noted that antidepressants are associated with withdrawal symptoms, but less than half (43%) used the term “withdrawal symptoms,” or similar. Of the nine guidelines that mentioned withdrawal symptoms, five used the term interchangeably with “discontinuation symptoms” and six used the term “discontinuation symptoms” only when discussing antidepressant withdrawal. In addition, six CPGs specifically stated that patients who stop antidepressants can experience withdrawal symptoms, and five stated that these symptoms also can occur in patients who are reducing or tapering their doses.

The type of withdrawal symptoms was mentioned in 10 CPGs, and the other 11 had no information on potential withdrawal symptoms, the researchers noted. Of the CPGs that mentioned symptoms specifically associated with withdrawal, the number of potential symptoms ranged from 4 to 39.

“None of the CPGs provided an exhaustive list of the potential withdrawal symptoms identified in the research literature,” the researchers wrote in their discussion.

Only four of the guidelines (19%) mentioned the overlap in symptoms between withdrawal from antidepressants and depression relapse, and only one provided guidance on distinguishing between the two conditions. Most of the symptoms of withdrawal, when described, were characterized as mild, brief, or self-limiting, the researchers noted.

“Being in withdrawal is a fundamentally different clinical situation than experiencing relapse, requiring two distinctly different treatment approaches,” the researchers emphasized. “Withdrawal reactions that are more severe and longer lasting than currently defined in the CPGs could risk getting misinterpreted as relapse, potentially leading to resumed unnecessary long-term antidepressant treatment in some patients,” they added.

The findings were limited by several factors including the inclusion only of guidelines from English-speaking countries, which may limit generalizability, the researchers noted. Other potential limitations include the subjective judgments involved in creating different guidelines, they said.

However, the results support the need for improved CPGs that help clinicians distinguish potential withdrawal reactions from depression relapse, and the need for more research on optimal dose reduction strategies for antidepressants, they concluded.

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

Current depression guidelines offer incomplete guidance for clinicians to identify antidepressant withdrawal, based on data from a review of 21 guidelines.

Previous research suggests that approximately half of patients who discontinue or decrease dosage of antidepressants experience withdrawal symptoms, wrote Anders Sørensen, MD, of Copenhagen University Hospital, and colleagues. These symptoms are diverse and may include flulike symptoms, fatigue, anxiety, and sensations of electric shock, they noted. Most withdrawal effects last for a few weeks, but some persist for months or years, sometimes described as persistent postwithdrawal disorder, they added.

“Symptoms of withdrawal and depression overlap considerably but constitute two fundamentally different clinical conditions, which makes it important to distinguish between the two,” the researchers emphasized.

In a study published in the Journal of Affective Disorders, the researchers identified 21 clinical practice guidelines (CPGs) for depression published between 1998 and 2022. The guidelines were published in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland, and New Zealand. They compared descriptions of withdrawal from antidepressants and calculated the proportion of CPGs with different information.

Overall, 15 of the 21 studies in the review (71%) noted that antidepressants are associated with withdrawal symptoms, but less than half (43%) used the term “withdrawal symptoms,” or similar. Of the nine guidelines that mentioned withdrawal symptoms, five used the term interchangeably with “discontinuation symptoms” and six used the term “discontinuation symptoms” only when discussing antidepressant withdrawal. In addition, six CPGs specifically stated that patients who stop antidepressants can experience withdrawal symptoms, and five stated that these symptoms also can occur in patients who are reducing or tapering their doses.

The type of withdrawal symptoms was mentioned in 10 CPGs, and the other 11 had no information on potential withdrawal symptoms, the researchers noted. Of the CPGs that mentioned symptoms specifically associated with withdrawal, the number of potential symptoms ranged from 4 to 39.

“None of the CPGs provided an exhaustive list of the potential withdrawal symptoms identified in the research literature,” the researchers wrote in their discussion.

Only four of the guidelines (19%) mentioned the overlap in symptoms between withdrawal from antidepressants and depression relapse, and only one provided guidance on distinguishing between the two conditions. Most of the symptoms of withdrawal, when described, were characterized as mild, brief, or self-limiting, the researchers noted.

“Being in withdrawal is a fundamentally different clinical situation than experiencing relapse, requiring two distinctly different treatment approaches,” the researchers emphasized. “Withdrawal reactions that are more severe and longer lasting than currently defined in the CPGs could risk getting misinterpreted as relapse, potentially leading to resumed unnecessary long-term antidepressant treatment in some patients,” they added.

The findings were limited by several factors including the inclusion only of guidelines from English-speaking countries, which may limit generalizability, the researchers noted. Other potential limitations include the subjective judgments involved in creating different guidelines, they said.

However, the results support the need for improved CPGs that help clinicians distinguish potential withdrawal reactions from depression relapse, and the need for more research on optimal dose reduction strategies for antidepressants, they concluded.

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

Current depression guidelines offer incomplete guidance for clinicians to identify antidepressant withdrawal, based on data from a review of 21 guidelines.

Previous research suggests that approximately half of patients who discontinue or decrease dosage of antidepressants experience withdrawal symptoms, wrote Anders Sørensen, MD, of Copenhagen University Hospital, and colleagues. These symptoms are diverse and may include flulike symptoms, fatigue, anxiety, and sensations of electric shock, they noted. Most withdrawal effects last for a few weeks, but some persist for months or years, sometimes described as persistent postwithdrawal disorder, they added.

“Symptoms of withdrawal and depression overlap considerably but constitute two fundamentally different clinical conditions, which makes it important to distinguish between the two,” the researchers emphasized.

In a study published in the Journal of Affective Disorders, the researchers identified 21 clinical practice guidelines (CPGs) for depression published between 1998 and 2022. The guidelines were published in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland, and New Zealand. They compared descriptions of withdrawal from antidepressants and calculated the proportion of CPGs with different information.

Overall, 15 of the 21 studies in the review (71%) noted that antidepressants are associated with withdrawal symptoms, but less than half (43%) used the term “withdrawal symptoms,” or similar. Of the nine guidelines that mentioned withdrawal symptoms, five used the term interchangeably with “discontinuation symptoms” and six used the term “discontinuation symptoms” only when discussing antidepressant withdrawal. In addition, six CPGs specifically stated that patients who stop antidepressants can experience withdrawal symptoms, and five stated that these symptoms also can occur in patients who are reducing or tapering their doses.

The type of withdrawal symptoms was mentioned in 10 CPGs, and the other 11 had no information on potential withdrawal symptoms, the researchers noted. Of the CPGs that mentioned symptoms specifically associated with withdrawal, the number of potential symptoms ranged from 4 to 39.

“None of the CPGs provided an exhaustive list of the potential withdrawal symptoms identified in the research literature,” the researchers wrote in their discussion.

Only four of the guidelines (19%) mentioned the overlap in symptoms between withdrawal from antidepressants and depression relapse, and only one provided guidance on distinguishing between the two conditions. Most of the symptoms of withdrawal, when described, were characterized as mild, brief, or self-limiting, the researchers noted.

“Being in withdrawal is a fundamentally different clinical situation than experiencing relapse, requiring two distinctly different treatment approaches,” the researchers emphasized. “Withdrawal reactions that are more severe and longer lasting than currently defined in the CPGs could risk getting misinterpreted as relapse, potentially leading to resumed unnecessary long-term antidepressant treatment in some patients,” they added.

The findings were limited by several factors including the inclusion only of guidelines from English-speaking countries, which may limit generalizability, the researchers noted. Other potential limitations include the subjective judgments involved in creating different guidelines, they said.

However, the results support the need for improved CPGs that help clinicians distinguish potential withdrawal reactions from depression relapse, and the need for more research on optimal dose reduction strategies for antidepressants, they concluded.

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

Clinicians generally regard major depressive disorder (MDD) and schizophrenia as 2 separate and distinct psychiatric brain disorders. However, despite some differences, those 2 psychiatric syndromes have numerous similarities across clinical features and neurobiologic parameters.

Biological similarities

Both disorders share the following variables:

• Highly genetic in etiology but with environmental influences and epigenetics
• Associated with childhood maltreatment, abuse, or neglect
• Disrupted neuroplasticity, especially shrinkage in hippocampal volume
• Significant drop in brain-derived neurotrophic factor resulting in decreased neurogenesis
• Extensive white matter pathology across interhemispheric and intrahemispheric bundles
• Increased levels of serum cortisol, a stress hormone and inflammatory biomarker
• Hypofrontal cerebral blood flow during acute episodes of both MDD and schizophrenia
• Reduced dendritic spines (in number and size) and impaired experiential neuroplasticity
• Neuroinflammation (eg, cytokines, tumor necrosis factor-alpha, C-reactive protein) during acute episodes
• Elevated oxidative stress biomarkers, indicating an increase in free radicals
• Overactive default mode network associated with ruminations in MDD and “daydreaming” in schizophrenia
• Decrease in gamma-aminobutyric acid (GABA) and its inhibitory activity, translating into dysregulation of glutamatergic pathways and other neurotransmitters
• Immune dysregulation and comorbid autoimmune disorders

Clinical similarities

• Psychotic symptoms, especially delusional thinking such as paranoia in schizophrenia and severe self-deprecation in MDD
• Significantly elevated lifetime suicide risk
• Cognitive impairment (more severe in schizophrenia across several cognitive functions)
• Similarity of depressive and negative symptoms (especially anhedonia, apathy, restricted facial expression, social withdrawal)
• Antidepressant medications im­-prove depressive and negative symptoms (though not completely in the case of negative symptoms of schizophrenia)
• Both have treatment-resistant subtypes that fail to respond to standard therapies
• Both are associated with comorbid generalized anxiety disorder
• Both are associated with comorbid obsessive-compulsive disorder
• Both are associated with serious alcohol and drug use
• Early mortality from general medical conditions, especially cardiovascular risks due to obesity, diabetes, hypertension, dyslipidemia
• Elevated risk of dementia with aging compared to the unaffected general population
• Opioids improve MDD and psychosis (buprenorphine in MDD and morphine in schizophrenia)
• Several second-generation antipsychotic medications are approved for both MDD and schizophrenia
• Electroconvulsive therapy is effective when pharmacotherapy fails in both MDD and schizophrenia

Biological differences

• Glutamate N-methyl-D-aspar­tate receptor antagonists (eg, ketamine) improve MDD but worsen schizophrenia
• Muscarinic agonists improve psychosis but worsen depression
• High pain threshold in schizophrenia (pain insensitivity) and low threshold in MDD (in which pain is a common comorbidity)
• Cortical thinning more severe in schizophrenia
• Hippocampal atrophy is reversible with successful treatment in MDD but not in schizophrenia
• Hypofrontality is reversible with remission in MDD but not in schizophrenia

Clinical differences

• Auditory and visual hallucinations are more common in schizophrenia than in MDD
• Anosognosia is common in schizophrenia but not in MDD
• Implausible delusions are more common in schizophrenia than in MDD
• Mood-congruent delusions are more common in MDD than in schizophrenia
• Sadness, crying, pessimism, and self-deprecation are common in MDD but not in schizophrenia
• Achieving full remission is more common in MDD than in schizophrenia
• Long-acting injectable medications are available for schizophrenia but not for MDD
• Evidence-based psychotherapy, without pharmacotherapy, is more likely to be effective in MDD than in schizophrenia

A transdiagnostic model of psychopathology

The significant overlap between MDD and schizophrenia should not be surprising. They are both generated by the same organ, the human brain, with disrupted neurochemical and physiological circuits in the brain.

The overlap is also consistent with the emerging transdiagnostic model of psychopathology.^1-9 This model proposes that there is a “core” genetic risk for psychopathology with different iterations. The transdiagnostic model is in stark contrast to the prevailing DSM-5, which categorizes psychiatric disorders in “silos,” as if they are completely independent from each other despite many shared features. This is highly debatable according to the substantial evidence that multiple psychiatric disorders share many genes that influence brain development in utero and predispose individuals to a variety of clinical symptoms in adolescence and young adulthood.

The origin of mental illness is being disentangled by emerging research, which is identifying the common links among the various disorders currently listed in DSM-5.¹⁰ However, the evolution of psychiatric diagnosis has come full circle from a single entity before DSM, to multiple entities with DSM, and now back to a unified transdiagnostic model that is rapidly emerging.¹¹ This has implications for the FDA’s persistent dogma that clinical trials for new drugs must be targeted for 1 of the DSM-5 categories, a flawed and narrow assumption. Given the accelerating body of evidence for a unified, transdiagnostic model, it makes much more sense for the FDA to approve medications that target a psychiatric symptom that is shared by multiple psychiatric conditions within a transdiagnostic clinical system. When medications are approved for a symptom regardless of a DSM diagnosis, the term “off-label” and its “stigma” will then fade into history, along with the malignant preauthorization racket that was invented by greedy insurance companies that exploit the off-label use of medications (even when an FDA-approved medication for the patient’s condition does not yet exist) simply to deny coverage, lower their expenses, and fatten their profits.

Clinicians generally regard major depressive disorder (MDD) and schizophrenia as 2 separate and distinct psychiatric brain disorders. However, despite some differences, those 2 psychiatric syndromes have numerous similarities across clinical features and neurobiologic parameters.

Biological similarities

Both disorders share the following variables:

• Highly genetic in etiology but with environmental influences and epigenetics
• Associated with childhood maltreatment, abuse, or neglect
• Disrupted neuroplasticity, especially shrinkage in hippocampal volume
• Significant drop in brain-derived neurotrophic factor resulting in decreased neurogenesis
• Extensive white matter pathology across interhemispheric and intrahemispheric bundles
• Increased levels of serum cortisol, a stress hormone and inflammatory biomarker
• Hypofrontal cerebral blood flow during acute episodes of both MDD and schizophrenia
• Reduced dendritic spines (in number and size) and impaired experiential neuroplasticity
• Neuroinflammation (eg, cytokines, tumor necrosis factor-alpha, C-reactive protein) during acute episodes
• Elevated oxidative stress biomarkers, indicating an increase in free radicals
• Overactive default mode network associated with ruminations in MDD and “daydreaming” in schizophrenia
• Decrease in gamma-aminobutyric acid (GABA) and its inhibitory activity, translating into dysregulation of glutamatergic pathways and other neurotransmitters
• Immune dysregulation and comorbid autoimmune disorders

Clinical similarities

• Psychotic symptoms, especially delusional thinking such as paranoia in schizophrenia and severe self-deprecation in MDD
• Significantly elevated lifetime suicide risk
• Cognitive impairment (more severe in schizophrenia across several cognitive functions)
• Similarity of depressive and negative symptoms (especially anhedonia, apathy, restricted facial expression, social withdrawal)
• Antidepressant medications im­-prove depressive and negative symptoms (though not completely in the case of negative symptoms of schizophrenia)
• Both have treatment-resistant subtypes that fail to respond to standard therapies
• Both are associated with comorbid generalized anxiety disorder
• Both are associated with comorbid obsessive-compulsive disorder
• Both are associated with serious alcohol and drug use
• Early mortality from general medical conditions, especially cardiovascular risks due to obesity, diabetes, hypertension, dyslipidemia
• Elevated risk of dementia with aging compared to the unaffected general population
• Opioids improve MDD and psychosis (buprenorphine in MDD and morphine in schizophrenia)
• Several second-generation antipsychotic medications are approved for both MDD and schizophrenia
• Electroconvulsive therapy is effective when pharmacotherapy fails in both MDD and schizophrenia

Biological differences

• Glutamate N-methyl-D-aspar­tate receptor antagonists (eg, ketamine) improve MDD but worsen schizophrenia
• Muscarinic agonists improve psychosis but worsen depression
• High pain threshold in schizophrenia (pain insensitivity) and low threshold in MDD (in which pain is a common comorbidity)
• Cortical thinning more severe in schizophrenia
• Hippocampal atrophy is reversible with successful treatment in MDD but not in schizophrenia
• Hypofrontality is reversible with remission in MDD but not in schizophrenia

Clinical differences

• Auditory and visual hallucinations are more common in schizophrenia than in MDD
• Anosognosia is common in schizophrenia but not in MDD
• Implausible delusions are more common in schizophrenia than in MDD
• Mood-congruent delusions are more common in MDD than in schizophrenia
• Sadness, crying, pessimism, and self-deprecation are common in MDD but not in schizophrenia
• Achieving full remission is more common in MDD than in schizophrenia
• Long-acting injectable medications are available for schizophrenia but not for MDD
• Evidence-based psychotherapy, without pharmacotherapy, is more likely to be effective in MDD than in schizophrenia

A transdiagnostic model of psychopathology

The significant overlap between MDD and schizophrenia should not be surprising. They are both generated by the same organ, the human brain, with disrupted neurochemical and physiological circuits in the brain.

The overlap is also consistent with the emerging transdiagnostic model of psychopathology.^1-9 This model proposes that there is a “core” genetic risk for psychopathology with different iterations. The transdiagnostic model is in stark contrast to the prevailing DSM-5, which categorizes psychiatric disorders in “silos,” as if they are completely independent from each other despite many shared features. This is highly debatable according to the substantial evidence that multiple psychiatric disorders share many genes that influence brain development in utero and predispose individuals to a variety of clinical symptoms in adolescence and young adulthood.

The origin of mental illness is being disentangled by emerging research, which is identifying the common links among the various disorders currently listed in DSM-5.¹⁰ However, the evolution of psychiatric diagnosis has come full circle from a single entity before DSM, to multiple entities with DSM, and now back to a unified transdiagnostic model that is rapidly emerging.¹¹ This has implications for the FDA’s persistent dogma that clinical trials for new drugs must be targeted for 1 of the DSM-5 categories, a flawed and narrow assumption. Given the accelerating body of evidence for a unified, transdiagnostic model, it makes much more sense for the FDA to approve medications that target a psychiatric symptom that is shared by multiple psychiatric conditions within a transdiagnostic clinical system. When medications are approved for a symptom regardless of a DSM diagnosis, the term “off-label” and its “stigma” will then fade into history, along with the malignant preauthorization racket that was invented by greedy insurance companies that exploit the off-label use of medications (even when an FDA-approved medication for the patient’s condition does not yet exist) simply to deny coverage, lower their expenses, and fatten their profits.

Clinicians generally regard major depressive disorder (MDD) and schizophrenia as 2 separate and distinct psychiatric brain disorders. However, despite some differences, those 2 psychiatric syndromes have numerous similarities across clinical features and neurobiologic parameters.

Biological similarities

Both disorders share the following variables:

• Highly genetic in etiology but with environmental influences and epigenetics
• Associated with childhood maltreatment, abuse, or neglect
• Disrupted neuroplasticity, especially shrinkage in hippocampal volume
• Significant drop in brain-derived neurotrophic factor resulting in decreased neurogenesis
• Extensive white matter pathology across interhemispheric and intrahemispheric bundles
• Increased levels of serum cortisol, a stress hormone and inflammatory biomarker
• Hypofrontal cerebral blood flow during acute episodes of both MDD and schizophrenia
• Reduced dendritic spines (in number and size) and impaired experiential neuroplasticity
• Neuroinflammation (eg, cytokines, tumor necrosis factor-alpha, C-reactive protein) during acute episodes
• Elevated oxidative stress biomarkers, indicating an increase in free radicals
• Overactive default mode network associated with ruminations in MDD and “daydreaming” in schizophrenia
• Decrease in gamma-aminobutyric acid (GABA) and its inhibitory activity, translating into dysregulation of glutamatergic pathways and other neurotransmitters
• Immune dysregulation and comorbid autoimmune disorders

Clinical similarities

• Psychotic symptoms, especially delusional thinking such as paranoia in schizophrenia and severe self-deprecation in MDD
• Significantly elevated lifetime suicide risk
• Cognitive impairment (more severe in schizophrenia across several cognitive functions)
• Similarity of depressive and negative symptoms (especially anhedonia, apathy, restricted facial expression, social withdrawal)
• Antidepressant medications im­-prove depressive and negative symptoms (though not completely in the case of negative symptoms of schizophrenia)
• Both have treatment-resistant subtypes that fail to respond to standard therapies
• Both are associated with comorbid generalized anxiety disorder
• Both are associated with comorbid obsessive-compulsive disorder
• Both are associated with serious alcohol and drug use
• Early mortality from general medical conditions, especially cardiovascular risks due to obesity, diabetes, hypertension, dyslipidemia
• Elevated risk of dementia with aging compared to the unaffected general population
• Opioids improve MDD and psychosis (buprenorphine in MDD and morphine in schizophrenia)
• Several second-generation antipsychotic medications are approved for both MDD and schizophrenia
• Electroconvulsive therapy is effective when pharmacotherapy fails in both MDD and schizophrenia

Biological differences

• Glutamate N-methyl-D-aspar­tate receptor antagonists (eg, ketamine) improve MDD but worsen schizophrenia
• Muscarinic agonists improve psychosis but worsen depression
• High pain threshold in schizophrenia (pain insensitivity) and low threshold in MDD (in which pain is a common comorbidity)
• Cortical thinning more severe in schizophrenia
• Hippocampal atrophy is reversible with successful treatment in MDD but not in schizophrenia
• Hypofrontality is reversible with remission in MDD but not in schizophrenia

Clinical differences

• Auditory and visual hallucinations are more common in schizophrenia than in MDD
• Anosognosia is common in schizophrenia but not in MDD
• Implausible delusions are more common in schizophrenia than in MDD
• Mood-congruent delusions are more common in MDD than in schizophrenia
• Sadness, crying, pessimism, and self-deprecation are common in MDD but not in schizophrenia
• Achieving full remission is more common in MDD than in schizophrenia
• Long-acting injectable medications are available for schizophrenia but not for MDD
• Evidence-based psychotherapy, without pharmacotherapy, is more likely to be effective in MDD than in schizophrenia

A transdiagnostic model of psychopathology

The significant overlap between MDD and schizophrenia should not be surprising. They are both generated by the same organ, the human brain, with disrupted neurochemical and physiological circuits in the brain.

The overlap is also consistent with the emerging transdiagnostic model of psychopathology.^1-9 This model proposes that there is a “core” genetic risk for psychopathology with different iterations. The transdiagnostic model is in stark contrast to the prevailing DSM-5, which categorizes psychiatric disorders in “silos,” as if they are completely independent from each other despite many shared features. This is highly debatable according to the substantial evidence that multiple psychiatric disorders share many genes that influence brain development in utero and predispose individuals to a variety of clinical symptoms in adolescence and young adulthood.

The origin of mental illness is being disentangled by emerging research, which is identifying the common links among the various disorders currently listed in DSM-5.¹⁰ However, the evolution of psychiatric diagnosis has come full circle from a single entity before DSM, to multiple entities with DSM, and now back to a unified transdiagnostic model that is rapidly emerging.¹¹ This has implications for the FDA’s persistent dogma that clinical trials for new drugs must be targeted for 1 of the DSM-5 categories, a flawed and narrow assumption. Given the accelerating body of evidence for a unified, transdiagnostic model, it makes much more sense for the FDA to approve medications that target a psychiatric symptom that is shared by multiple psychiatric conditions within a transdiagnostic clinical system. When medications are approved for a symptom regardless of a DSM diagnosis, the term “off-label” and its “stigma” will then fade into history, along with the malignant preauthorization racket that was invented by greedy insurance companies that exploit the off-label use of medications (even when an FDA-approved medication for the patient’s condition does not yet exist) simply to deny coverage, lower their expenses, and fatten their profits.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.