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A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

A newly discovered vascular brain barrier that blocks the passage of inflammatory molecules triggered by gut bacteria may be why patients with inflammatory bowel disease (IBD) are at increased risk for certain mental health disorders, including anxiety and depression, early research suggests.

The discovery, which was based on a preclinical model, could lead to new therapeutic targets that could have applications for both gastrointestinal and psychiatric conditions, investigators note.

The research team, which was led by immunologist Maria Rescigno, PhD, and neuroscientist Simona Lodato, PhD, both from Humanitas University, Milan, notes that the barrier resides in the choroid plexus, a region of the brain that is involved in filtering cerebrospinal fluid. The researchers found that the region closes in response to inflammatory molecules produced in reaction to the presence of intestinal bacteria in patients with gut disorders.

Dr. Lodato said in an interview that the brain’s choroid plexus vascular barrier, along with another barrier between the gut and liver, known as the gut vascular barrier, appear to control the movement of molecules along the gut-brain axis.

“We show that in addition to the epithelial barrier in the choroid plexus, there is a functional vascular barrier that only becomes evident in blocking entry of various inflammatory molecules under conditions of systemic inflammation,” Dr. Lodato said.

“This interruption of the gut-brain interaction has developed to protect the brain from inflammation. Why this happens is not yet known, but it is likely to prevent epileptic seizures and imbalanced neuronal activity,” added Dr. Rescigno.

The study was published online October 22 in Science.
 

The gut a root cause of mental illness?

Nearly 40% of patients with IBD also experience depression and anxiety. It was once thought that these conditions arose because of patients’ difficulties in coping with their disease, said Dr. Rescigno.

“People with these disorders conventionally thought to be caused by an imbalance in the brain may actually find the root cause is located in the intestine. This is the first time these symptoms have been associated with the choroid plexus vascular brain barrier and its closure,” she noted.

Dr. Rescigno added that subtle, rather than overt, inflammation may be all that’s required for closure of the choroid plexus and the subsequent effects on mental health.

In 2015, Dr. Rescigno’s group first described the gut vascular barrier that protects the systemic circulation from gut bacteria or associated bacteria-derived molecules. During intestinal inflammation, such as occurs in IBD, this barrier is compromised and becomes more permeable. This allows microbes to pass across the epithelium of the gut barrier and enter the systemic circulation, including the liver and spleen, explained Dr. Rescigno.

Dr. Rescigno and Dr. Lodato then explored whether this systemic inflammatory condition was connected to the brain along a gut-brain axis and found that it was.

The researchers tested the hypothesis that central nervous system symptoms may be due to vascular changes at the interface between the gut or the brain and elsewhere in the body.

“We set out to test whether opening of the gut vascular barrier would allow gut bacteria to trigger the release of inflammatory molecules that spread to more distant areas, possibly leading to a deficiency of certain nutrients and precipitating mental disorders,” they said.

An experimental preclinical model of the choroid plexus vascular barrier closure led to anxiety-like behavior, as well as short-term memory loss. That this behavior occurred independently of inflammation suggested that it was likely a response to closure itself, they note.

In the noninflammatory state, the epithelium of the choroid plexus filters molecules. Those that are ≤70 kDa are allowed to pass through to the brain. However, the investigators found that during systemic inflammation, this filtration stops, and the blood capillaries of the choroid plexus prevent entry of inflammatory molecules such as cytokines.

Dr. Lodato speculated that when the vascular barrier of the choroid plexus shuts off during the systemic inflammatory state, it responds by bathing the brain in cerebrospinal fluid.

“When the choroid plexus closes, like a door slamming shut, then communication between the brain and the rest of the body is halted. This means that the brain is deprived of certain nutrients and other beneficial molecules that usually enter via the cerebrospinal fluid or enriched of potentially dangerous ones, as drainage could also be affected,” she said.

If confirmed in further studies, these results may open the way to new interventions.
 

‘A significant leap forward’

Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”

Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.

“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.

“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.

“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.

Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”

This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”

To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.

“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.

Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”

Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

The use of race/ethnicity in medicine to explain and interpret pulmonary function test (PFT) differences between individuals may contribute to biased medical care and research. Furthermore, it may perpetuate health disparities and structural racism, according to a study published in the journal CHEST®.

Current practices of PFT measurement and interpretation, are imperfect in their ability to accurately describe the relationship between function and health outcomes, according to Nirav R. Bhakta, MD, University of California,San Francisco, and colleagues.

The authors summarized arguments against using race-specific equations, while voicing genuine concerns about removing race from PFT interpretations, and described knowledge gaps and critical questions needing to be addressed for remediation of health disparities.

“Leaving out the perspectives of practicing pulmonologists and physiologists has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain,” Dr. Bhakta said in an interview.
 

A lesson in history

Tracing the history of spirometry, the authors stated that observations about vital lung capacity showing differences attributable to height, age, sex, and occupation (e.g., typesetter vs. firefighter) were then extended to include social classes and ultimately race. Whites showed greater average vital capacity for the same sex, height, and age than non-Whites.

While some investigators pointed to environmental sources (such as early life nutrition, respiratory illness, air pollution, exercise, and altitude), research into their mechanisms and magnitudes of effect was not pursued, but rather “a narrative of innate differences took hold,” Dr. Bhakta and colleagues reported.

That sort of narrative risks comparison with those used to uphold slavery and structural racism in the past. More recently, such a narrative was used to deny disability claims of Welsh versus English White miners, and was expanded to interpret algorithms designed to predict expected lung function.
 

Use of standing height questioned

The current practice of using normalized standard height for lung function comparisons misses racial and ethnic differences in the proportion of sitting height to standing height shown in multiple studies, the authors stated. These comparisons may ignore effects on standing height of early-life nutrition, genetics, lung-specific factors such as respiratory infections and exposures to indoor and outdoor pollution, physical activity, and high altitude. Using sitting height instead of standing height reduces lung volume differences up to 50% between White and Black populations, they noted, and socioeconomic variables, such as poverty and immigration status, accounted further for the differences seen. Population differences disappeared by as much as 90% when chest measurements used to estimate surface area or volume were more finely detailed.

The researchers warned, however, that, “because current clinical and policy algorithms rely so heavily on the comparison of an individual’s observed lung function to that which is expected for similar people without typical respiratory disease, an abrupt change to not using race/ethnicity, if not paired with education and a reform of existing algorithms and policies, is also expected to have risks on average to groups of non-White individuals.”

That could lead to potential challenges for some groups ranging from the ability to obtain employment in certain occupations, to being considered for potentially curative lung resections, or having access to home assisted ventilation and rehabilitation programs. “An abrupt change to not using race/ethnicity and taking a society’s overall average as the reference range also has the potential to lead to delayed care, denial of disability benefits, and higher life insurance premiums to White individuals.”
 

Evidence base is limited

“Although evidence demonstrates differences in lung function between racial/ethnic groups, the premise that dividing lung function interpretation up by racial/ethnic background is helpful in the clinical setting is not a proven one.” The authors cited some evidence that lung function interpretation without consideration of race/ethnicity has superior prognostic ability. In addition, research has shown only a weak relationship between lung function and work ability, according to the authors. More appropriate ways of assessing expected lung function for an individual in the absence of a diagnoses are under study.

Offering an alternative

As an alternative to race, Dr. Bhakta and colleagues proposed using a range of values that include individuals across many global populations while still adjusting for sex, age, and height. The resultant value would represent a diverse population average and widen the limits of normal that can be expected in otherwise-healthy people.

The approach would include PFTs with other factors for clinical decision-making, but would allow clinicians and patients to appreciate the limitations of interpretation based on comparison to reference values. However, such an approach may miss pathophysiologically reduced lung function in some individuals, in which case lifesaving therapies, such as chemotherapy, lung cancer resection, and bone marrow transplantation could be withheld. In other instances the consequence would be overtesting and diagnosis, they acknowledged.

The authors further discussed general concerns about the use of race in interpretation of PFTs, addressing limits/considerations as well as knowledge and practice gaps.

For example, one particular concern involves the fact that race does not capture acculturation and mixed ancestry. The limit/consideration is the need to discover mechanisms for differences and to suggest societal interventions, and the knowledge gap pertains to ignorance regarding mechanisms leading to differences in lung function.

For the concern that race is not a proxy for an individual’s genetics, the limit/consideration is that race captures only some genetics and the gap is the need for better genetic information. As an antidote to over reliance on lung function thresholds (without supporting data), they urged outcomes-based standards rather than comparisons with reference populations.
 

New thinking needed

Dr. Bhakta and colleagues pointed out that the forced expiratory volume in 1 second/forced vital capacity ratios important for diagnosis of obstructive lung disease are similar between racial/ethnic categories, underscoring the need for education about limitations of thresholds and reference values with regard to race, particularly as they are used to detect mild disease.

Ignoring race, on the other hand, can lead to unnecessary testing and treatment (with concomitant side effects), and anxiety.

“Reporting through race-based algorithms in the PFT laboratory risks portraying racial disparities as innate and immutable. By anchoring on the improved prediction of lung function from racial/ethnic-specific reference equations, we miss how the significant residual variation still leaves much uncertainty about the expected value for an individual,” the authors concluded. “Given their origin and historical and current use in society, these racial/ethnic labels are better used to identify the effects of structural racism on respiratory health in research and ensure adequate representation in research, rather than in clinical algorithms.”

One of the authors is a speaker for MGC Diagnostics. The others indicated that they had no relevant disclosures.

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

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

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

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

The Biden administration on Nov. 4 unveiled its rule to require most of the country’s larger employers to mandate workers be fully vaccinated against COVID-19, but set a Jan. 4 deadline, avoiding the busy holiday season.

The White House also shifted the time lines for earlier mandates applying to federal workers and contractors to Jan. 4. And the same deadline applies to a new separate rule for health care workers.

The new rules are meant to preempt “any inconsistent state or local laws,” including bans and limits on employers’ authority to require vaccination, masks, or testing, the White House said in a statement.

The rule on employers from the Occupational Safety and Health Administration will apply to organizations with 100 or more employees. These employers will need to make sure each worker is fully vaccinated or tests for COVID-19 on at least a weekly basis. The OSHA rule will also require that employers provide paid time for employees to get vaccinated and ensure that all unvaccinated workers wear a face mask in the workplace. This rule will cover 84 million employees. The OSHA rule will not apply to workplaces covered by either the Centers for Medicare & Medicaid Services rule or the federal contractor vaccination requirement

“The virus will not go away by itself, or because we wish it away: We have to act,” President Joe Biden said in a statement. “Vaccination is the single best pathway out of this pandemic.”

Mandates were not the preferred route to managing the pandemic, he said.

“Too many people remain unvaccinated for us to get out of this pandemic for good,” he said. “So I instituted requirements – and they are working.”

The White House said 70% percent of U.S. adults are now fully vaccinated – up from less than 1% when Mr. Biden took office in January.

The CMS vaccine rule is meant to cover more than 17 million workers and about 76,000 medical care sites, including hospitals, ambulatory surgery centers, nursing homes, dialysis facilities, home health agencies, and long-term care facilities. The rule will apply to employees whether their positions involve patient care or not.

Unlike the OSHA mandate, the one for health care workers will not offer the option of frequent COVID-19 testing instead of vaccination. There is a “higher bar” for health care workers, given their role in treating patients, so the mandate allows only for vaccination or limited exemptions, a senior administration official said on Nov. 3 during a call with reporters.

The CMS rule includes a “range of remedies,” including penalties and denial of payment for health care facilities that fail to meet the vaccine mandate. CMS could theoretically cut off hospitals and other medical organizations for failure to comply, but that would be a “last resort,” a senior administration official said. CMS will instead work with health care facilities to help them comply with the federal rule on vaccination of medical workers.

The new CMS rules apply only to Medicare- and Medicaid-certified centers and organizations. The rule does not directly apply to other health care entities, such as doctor’s offices, that are not regulated by CMS.

“Most states have separate licensing requirements for health care staff and health care providers that would be applicable to physician office staff and other staff in small health care entities that are not subject to vaccination requirements under this IFC,” CMS said in the rule.

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

Oral drug administration was significantly associated with a shorter length of stay for patients treated for headache in the emergency department setting, based on data from approximately 7,000 patients.

Headache is the fourth-most common chief complaint in the ED, accounting for approximately 3% of all ED visits, said Philip Wang, a medical student at the Cleveland Clinic, in a presentation at the annual meeting of the American College of Emergency Physicians.

A variety of pharmacotherapies are used to manage headache, which leads to a range of resource use, he said.

To understand the association between route of drug administration and length of ED stay, Mr. Wang and colleagues reviewed data from 7,233 visits by 6,715 patients at any of the 21 Cleveland Clinic Health System EDs in 2018 with headache as the primary discharge diagnosis. Patients admitted to the hospital were excluded; those treated with opioids, antiemetics, and/or NSAIDs were included. The average age of the study population was 31 years, 57% were White, and approximately half were Medicaid or Medicare patients.

Approximately 68% of patients received antiemetics, 66.8% received NSAIDs, and 9.8% received opioids. Approximately 42% of patients received parenteral-only treatment and 42% received oral-only treatment; 15% received mixed treatment. The average length of ED stay was 202 minutes.

In a multivariate analysis adjusted for sex, age, income, race, insurance status, ED type, and arrival time, treatment with oral drugs only was associated with an 11% reduction of length of stay, compared with treatment with parenteral medication only (P < .001). However, the length of stay for patients treated with mixed route of administration was 10% longer, compared with parenteral only (P < .001).

In terms of drug class (a secondary outcome), patients treated with opioids had a 10% increase in length of stay (P < .01) and those treated with antiemetics had a 14% increase in length of stay; however, patients treated with NSAIDs had a 7% decrease in length of stay.

The study findings were limited in part by the challenge of isolating patients presenting with a primary headache diagnosis, Mr. Wang noted in the presentation.

The challenge of controlling for all the potential factors impacting length of stay, which is “provider, resource, and situation dependent,” is an additional limitation, he said.

However, the results show that route of administration has a significant impact on length of ED stay in patients presenting with headache, he concluded.

The study received no outside funding. The researchers disclosed no relevant financial relationships.

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

Oral drug administration was significantly associated with a shorter length of stay for patients treated for headache in the emergency department setting, based on data from approximately 7,000 patients.

Headache is the fourth-most common chief complaint in the ED, accounting for approximately 3% of all ED visits, said Philip Wang, a medical student at the Cleveland Clinic, in a presentation at the annual meeting of the American College of Emergency Physicians.

A variety of pharmacotherapies are used to manage headache, which leads to a range of resource use, he said.

To understand the association between route of drug administration and length of ED stay, Mr. Wang and colleagues reviewed data from 7,233 visits by 6,715 patients at any of the 21 Cleveland Clinic Health System EDs in 2018 with headache as the primary discharge diagnosis. Patients admitted to the hospital were excluded; those treated with opioids, antiemetics, and/or NSAIDs were included. The average age of the study population was 31 years, 57% were White, and approximately half were Medicaid or Medicare patients.

Approximately 68% of patients received antiemetics, 66.8% received NSAIDs, and 9.8% received opioids. Approximately 42% of patients received parenteral-only treatment and 42% received oral-only treatment; 15% received mixed treatment. The average length of ED stay was 202 minutes.

In a multivariate analysis adjusted for sex, age, income, race, insurance status, ED type, and arrival time, treatment with oral drugs only was associated with an 11% reduction of length of stay, compared with treatment with parenteral medication only (P < .001). However, the length of stay for patients treated with mixed route of administration was 10% longer, compared with parenteral only (P < .001).

In terms of drug class (a secondary outcome), patients treated with opioids had a 10% increase in length of stay (P < .01) and those treated with antiemetics had a 14% increase in length of stay; however, patients treated with NSAIDs had a 7% decrease in length of stay.

The study findings were limited in part by the challenge of isolating patients presenting with a primary headache diagnosis, Mr. Wang noted in the presentation.

The challenge of controlling for all the potential factors impacting length of stay, which is “provider, resource, and situation dependent,” is an additional limitation, he said.

However, the results show that route of administration has a significant impact on length of ED stay in patients presenting with headache, he concluded.

The study received no outside funding. The researchers disclosed no relevant financial relationships.

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

Oral drug administration was significantly associated with a shorter length of stay for patients treated for headache in the emergency department setting, based on data from approximately 7,000 patients.

Headache is the fourth-most common chief complaint in the ED, accounting for approximately 3% of all ED visits, said Philip Wang, a medical student at the Cleveland Clinic, in a presentation at the annual meeting of the American College of Emergency Physicians.

A variety of pharmacotherapies are used to manage headache, which leads to a range of resource use, he said.

To understand the association between route of drug administration and length of ED stay, Mr. Wang and colleagues reviewed data from 7,233 visits by 6,715 patients at any of the 21 Cleveland Clinic Health System EDs in 2018 with headache as the primary discharge diagnosis. Patients admitted to the hospital were excluded; those treated with opioids, antiemetics, and/or NSAIDs were included. The average age of the study population was 31 years, 57% were White, and approximately half were Medicaid or Medicare patients.

Approximately 68% of patients received antiemetics, 66.8% received NSAIDs, and 9.8% received opioids. Approximately 42% of patients received parenteral-only treatment and 42% received oral-only treatment; 15% received mixed treatment. The average length of ED stay was 202 minutes.

In a multivariate analysis adjusted for sex, age, income, race, insurance status, ED type, and arrival time, treatment with oral drugs only was associated with an 11% reduction of length of stay, compared with treatment with parenteral medication only (P < .001). However, the length of stay for patients treated with mixed route of administration was 10% longer, compared with parenteral only (P < .001).

In terms of drug class (a secondary outcome), patients treated with opioids had a 10% increase in length of stay (P < .01) and those treated with antiemetics had a 14% increase in length of stay; however, patients treated with NSAIDs had a 7% decrease in length of stay.

The study findings were limited in part by the challenge of isolating patients presenting with a primary headache diagnosis, Mr. Wang noted in the presentation.

The challenge of controlling for all the potential factors impacting length of stay, which is “provider, resource, and situation dependent,” is an additional limitation, he said.

However, the results show that route of administration has a significant impact on length of ED stay in patients presenting with headache, he concluded.

The study received no outside funding. The researchers disclosed no relevant financial relationships.

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

The Food and Drug Administration on Oct. 27 announced stronger safety requirements for breast implants, restricting sales of implants only to providers and health facilities that review potential risks of the devices with patients before surgery, via a “Patient Decision Checklist.” The agency also placed a boxed warning – the strongest warning that the FDA requires – on all legally marketed breast implants.

“Protecting patients’ health when they are treated with a medical device is our most important priority,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in a press release. “In recent years, the FDA has sought more ways to increase patients’ access to clear and understandable information about the benefits and risks of breast implants. By strengthening the safety requirements for manufacturers, the FDA is working to close information gaps for anyone who may be considering breast implant surgery.”

This announcement comes 10 years after the FDA issued a comprehensive safety update on silicone gel–filled implants, which reported a possible association between these devices and anaplastic large cell lymphoma (ALCL). The studies reviewed in the 2011 document also noted that a “significant percentage of women who receive silicone gel–filled breast implants experience complications and adverse outcomes,” the most common being repeat operation, implant removal, rupture, or capsular contracture (scar tissue tightening around the implant).

Breast augmentation has been one of the top five cosmetic procedures in the United States since 2006, according to the American Society for Plastic Surgery, with more than 400,000 people getting breast implants in 2019. Nearly 300,000 were for cosmetic reasons, and more than 100,000 were for breast reconstruction after mastectomies.

In 2019, the FDA proposed adding a boxed warning for breast implants, stating that the devices do not last an entire lifetime; that over time the risk for complications increases; and that breast implants have been associated with ALCL, and also may be associated with systemic symptoms such as fatigue, joint pain, and brain fog. The Oct. 27 FDA action now requires that manufacturers update breast implant packaging to include that information in a boxed warning, as well as the following:

• A patient-decision checklist
• Updated silicone gel–filled breast implant rupture screening recommendations
• A device description including materials used in the device
• Patient device ID cards

The updated label changes must be present on manufacturers’ websites in 30 days, the FDA said.

The new requirements have received largely positive reactions from both physicians and patient organizations. In an emailed statement to this news organization, Lynn Jeffers, MD, MBA, the immediate past president of the American Society of Plastic Surgeons, said that “ASPS has always supported patients being fully informed about their choices and the risks, benefits, and alternatives of the options available. “We look forward to our continued collaboration with the FDA on the safety of implants and other devices.”

Maria Gmitro, president and cofounder of the Breast Implant Safety Alliance, an all-volunteer nonprofit based in Charleston, S.C., said that some of the language in the patient checklist could be stronger, especially when referring to breast implant–associated ALCL.

To inform patients of risks more clearly, “it’s the words like ‘associated with’ that we feel need to be stronger” she said in an interview. She also noted that women who already have breast implants may not be aware of these potential complications, which these new FDA requirements do not address.

But overall, the nonprofit was “thrilled” with the announcement, Ms. Gmitro said. “Placing restrictions on breast implants is a really big step, and we applaud the FDA’s efforts. This is information that every patient considering breast implants should know, and we’ve been advocating for better informed consent.”

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

The Food and Drug Administration on Oct. 27 announced stronger safety requirements for breast implants, restricting sales of implants only to providers and health facilities that review potential risks of the devices with patients before surgery, via a “Patient Decision Checklist.” The agency also placed a boxed warning – the strongest warning that the FDA requires – on all legally marketed breast implants.

“Protecting patients’ health when they are treated with a medical device is our most important priority,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in a press release. “In recent years, the FDA has sought more ways to increase patients’ access to clear and understandable information about the benefits and risks of breast implants. By strengthening the safety requirements for manufacturers, the FDA is working to close information gaps for anyone who may be considering breast implant surgery.”

This announcement comes 10 years after the FDA issued a comprehensive safety update on silicone gel–filled implants, which reported a possible association between these devices and anaplastic large cell lymphoma (ALCL). The studies reviewed in the 2011 document also noted that a “significant percentage of women who receive silicone gel–filled breast implants experience complications and adverse outcomes,” the most common being repeat operation, implant removal, rupture, or capsular contracture (scar tissue tightening around the implant).

Breast augmentation has been one of the top five cosmetic procedures in the United States since 2006, according to the American Society for Plastic Surgery, with more than 400,000 people getting breast implants in 2019. Nearly 300,000 were for cosmetic reasons, and more than 100,000 were for breast reconstruction after mastectomies.

In 2019, the FDA proposed adding a boxed warning for breast implants, stating that the devices do not last an entire lifetime; that over time the risk for complications increases; and that breast implants have been associated with ALCL, and also may be associated with systemic symptoms such as fatigue, joint pain, and brain fog. The Oct. 27 FDA action now requires that manufacturers update breast implant packaging to include that information in a boxed warning, as well as the following:

• A patient-decision checklist
• Updated silicone gel–filled breast implant rupture screening recommendations
• A device description including materials used in the device
• Patient device ID cards

The updated label changes must be present on manufacturers’ websites in 30 days, the FDA said.

The new requirements have received largely positive reactions from both physicians and patient organizations. In an emailed statement to this news organization, Lynn Jeffers, MD, MBA, the immediate past president of the American Society of Plastic Surgeons, said that “ASPS has always supported patients being fully informed about their choices and the risks, benefits, and alternatives of the options available. “We look forward to our continued collaboration with the FDA on the safety of implants and other devices.”

Maria Gmitro, president and cofounder of the Breast Implant Safety Alliance, an all-volunteer nonprofit based in Charleston, S.C., said that some of the language in the patient checklist could be stronger, especially when referring to breast implant–associated ALCL.

To inform patients of risks more clearly, “it’s the words like ‘associated with’ that we feel need to be stronger” she said in an interview. She also noted that women who already have breast implants may not be aware of these potential complications, which these new FDA requirements do not address.

But overall, the nonprofit was “thrilled” with the announcement, Ms. Gmitro said. “Placing restrictions on breast implants is a really big step, and we applaud the FDA’s efforts. This is information that every patient considering breast implants should know, and we’ve been advocating for better informed consent.”

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

The Food and Drug Administration on Oct. 27 announced stronger safety requirements for breast implants, restricting sales of implants only to providers and health facilities that review potential risks of the devices with patients before surgery, via a “Patient Decision Checklist.” The agency also placed a boxed warning – the strongest warning that the FDA requires – on all legally marketed breast implants.

“Protecting patients’ health when they are treated with a medical device is our most important priority,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in a press release. “In recent years, the FDA has sought more ways to increase patients’ access to clear and understandable information about the benefits and risks of breast implants. By strengthening the safety requirements for manufacturers, the FDA is working to close information gaps for anyone who may be considering breast implant surgery.”

This announcement comes 10 years after the FDA issued a comprehensive safety update on silicone gel–filled implants, which reported a possible association between these devices and anaplastic large cell lymphoma (ALCL). The studies reviewed in the 2011 document also noted that a “significant percentage of women who receive silicone gel–filled breast implants experience complications and adverse outcomes,” the most common being repeat operation, implant removal, rupture, or capsular contracture (scar tissue tightening around the implant).

Breast augmentation has been one of the top five cosmetic procedures in the United States since 2006, according to the American Society for Plastic Surgery, with more than 400,000 people getting breast implants in 2019. Nearly 300,000 were for cosmetic reasons, and more than 100,000 were for breast reconstruction after mastectomies.

In 2019, the FDA proposed adding a boxed warning for breast implants, stating that the devices do not last an entire lifetime; that over time the risk for complications increases; and that breast implants have been associated with ALCL, and also may be associated with systemic symptoms such as fatigue, joint pain, and brain fog. The Oct. 27 FDA action now requires that manufacturers update breast implant packaging to include that information in a boxed warning, as well as the following:

• A patient-decision checklist
• Updated silicone gel–filled breast implant rupture screening recommendations
• A device description including materials used in the device
• Patient device ID cards

The updated label changes must be present on manufacturers’ websites in 30 days, the FDA said.

The new requirements have received largely positive reactions from both physicians and patient organizations. In an emailed statement to this news organization, Lynn Jeffers, MD, MBA, the immediate past president of the American Society of Plastic Surgeons, said that “ASPS has always supported patients being fully informed about their choices and the risks, benefits, and alternatives of the options available. “We look forward to our continued collaboration with the FDA on the safety of implants and other devices.”

Maria Gmitro, president and cofounder of the Breast Implant Safety Alliance, an all-volunteer nonprofit based in Charleston, S.C., said that some of the language in the patient checklist could be stronger, especially when referring to breast implant–associated ALCL.

To inform patients of risks more clearly, “it’s the words like ‘associated with’ that we feel need to be stronger” she said in an interview. She also noted that women who already have breast implants may not be aware of these potential complications, which these new FDA requirements do not address.

But overall, the nonprofit was “thrilled” with the announcement, Ms. Gmitro said. “Placing restrictions on breast implants is a really big step, and we applaud the FDA’s efforts. This is information that every patient considering breast implants should know, and we’ve been advocating for better informed consent.”

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

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

zoranm/Getty Images

The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

zoranm/Getty Images

The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

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The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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