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Now USPSTF also suggests start CRC screening at age 45
that is open for public comment.
“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.
The recommendation is that all adults aged 45-75 years be screened for CRC.
This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.
For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.
Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
Mounting pressure
The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.
Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).
The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.
“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”
Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.
The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.
The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.
“The right test is the one a patient will do,” Dr. Barry commented.
Defining populations
CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.
“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”
Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
Limit screening to those at higher risk
In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.
As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.
The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”
Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
A version of this article originally appeared on Medscape.com.
Clinicians and researchers have actively debated the pros and cons of lowering the screening age to 45 years since 2018, when the American Cancer Society released its colorectal cancer (CRC) screening guidelines. The most compelling argument in support of lowering the screening age is that recent data from Surveillance Epidemiology and End Results (SEER) show that the CRC incidence rates in 45- to 50-year-olds are similar to rates seen in 50- to 54-year-olds about 20 years ago, when the first guidelines to initiate screening at age 50 were widely established. Termed early-onset CRC (EOCRC), the underlying reasons for this increase are not completely understood, and while the absolute numbers of EOCRC cases are smaller than in older age groups, modeling studies show that screening this age group is both efficient and effective.
Over the last 20 years we have made major strides in reducing the incidence and mortality from CRC in ages 50 years and older, and now we must rise to the challenge of delivering CRC screening to this younger group in order to see similar dividends over time and curb the rising incidence curve of EOCRC. And we must do so without direct evidence to guide us as to the magnitude of the benefit of screening this younger group, the best modality to use, or tools to risk stratify who is likely to benefit from screening in this group. We must also be careful not to worsen racial and geographic disparities in CRC screening, which already exist for African Americans, Native Americans, and other minorities and rural residents. Finally, even though the goal posts are changing, our target remains to get to 80% screening rates for all age groups, and not neglect the currently underscreened 50- to 75-year-olds, who are at a much higher risk of CRC than their younger counterparts.
Aasma Shaukat, MD, MPH, is an investigator, Center for Care Delivery and Outcomes Research, section chief and staff physician, GI section, Minneapolis VA Health Care System; staff physician, Fairview University of Minnesota Medical Center, Minneapolis; and professor, University of Minnesota department of medicine, division of gastroenterology, Minneapolis. She has no conflicts of interest.
Clinicians and researchers have actively debated the pros and cons of lowering the screening age to 45 years since 2018, when the American Cancer Society released its colorectal cancer (CRC) screening guidelines. The most compelling argument in support of lowering the screening age is that recent data from Surveillance Epidemiology and End Results (SEER) show that the CRC incidence rates in 45- to 50-year-olds are similar to rates seen in 50- to 54-year-olds about 20 years ago, when the first guidelines to initiate screening at age 50 were widely established. Termed early-onset CRC (EOCRC), the underlying reasons for this increase are not completely understood, and while the absolute numbers of EOCRC cases are smaller than in older age groups, modeling studies show that screening this age group is both efficient and effective.
Over the last 20 years we have made major strides in reducing the incidence and mortality from CRC in ages 50 years and older, and now we must rise to the challenge of delivering CRC screening to this younger group in order to see similar dividends over time and curb the rising incidence curve of EOCRC. And we must do so without direct evidence to guide us as to the magnitude of the benefit of screening this younger group, the best modality to use, or tools to risk stratify who is likely to benefit from screening in this group. We must also be careful not to worsen racial and geographic disparities in CRC screening, which already exist for African Americans, Native Americans, and other minorities and rural residents. Finally, even though the goal posts are changing, our target remains to get to 80% screening rates for all age groups, and not neglect the currently underscreened 50- to 75-year-olds, who are at a much higher risk of CRC than their younger counterparts.
Aasma Shaukat, MD, MPH, is an investigator, Center for Care Delivery and Outcomes Research, section chief and staff physician, GI section, Minneapolis VA Health Care System; staff physician, Fairview University of Minnesota Medical Center, Minneapolis; and professor, University of Minnesota department of medicine, division of gastroenterology, Minneapolis. She has no conflicts of interest.
Clinicians and researchers have actively debated the pros and cons of lowering the screening age to 45 years since 2018, when the American Cancer Society released its colorectal cancer (CRC) screening guidelines. The most compelling argument in support of lowering the screening age is that recent data from Surveillance Epidemiology and End Results (SEER) show that the CRC incidence rates in 45- to 50-year-olds are similar to rates seen in 50- to 54-year-olds about 20 years ago, when the first guidelines to initiate screening at age 50 were widely established. Termed early-onset CRC (EOCRC), the underlying reasons for this increase are not completely understood, and while the absolute numbers of EOCRC cases are smaller than in older age groups, modeling studies show that screening this age group is both efficient and effective.
Over the last 20 years we have made major strides in reducing the incidence and mortality from CRC in ages 50 years and older, and now we must rise to the challenge of delivering CRC screening to this younger group in order to see similar dividends over time and curb the rising incidence curve of EOCRC. And we must do so without direct evidence to guide us as to the magnitude of the benefit of screening this younger group, the best modality to use, or tools to risk stratify who is likely to benefit from screening in this group. We must also be careful not to worsen racial and geographic disparities in CRC screening, which already exist for African Americans, Native Americans, and other minorities and rural residents. Finally, even though the goal posts are changing, our target remains to get to 80% screening rates for all age groups, and not neglect the currently underscreened 50- to 75-year-olds, who are at a much higher risk of CRC than their younger counterparts.
Aasma Shaukat, MD, MPH, is an investigator, Center for Care Delivery and Outcomes Research, section chief and staff physician, GI section, Minneapolis VA Health Care System; staff physician, Fairview University of Minnesota Medical Center, Minneapolis; and professor, University of Minnesota department of medicine, division of gastroenterology, Minneapolis. She has no conflicts of interest.
that is open for public comment.
“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.
The recommendation is that all adults aged 45-75 years be screened for CRC.
This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.
For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.
Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
Mounting pressure
The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.
Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).
The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.
“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”
Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.
The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.
The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.
“The right test is the one a patient will do,” Dr. Barry commented.
Defining populations
CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.
“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”
Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
Limit screening to those at higher risk
In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.
As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.
The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”
Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
A version of this article originally appeared on Medscape.com.
that is open for public comment.
“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.
The recommendation is that all adults aged 45-75 years be screened for CRC.
This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.
For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.
Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
Mounting pressure
The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.
Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).
The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.
“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”
Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.
The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.
The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.
“The right test is the one a patient will do,” Dr. Barry commented.
Defining populations
CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.
“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”
Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
Limit screening to those at higher risk
In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.
As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.
The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”
Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
A version of this article originally appeared on Medscape.com.
Few women hospitalized for influenza have been vaccinated
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Acute HIV cases double in ED. Is COVID-19 responsible?
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
Tofacitinib retreatment effective for ulcerative colitis
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Trump signs CR with Medicare loan relief
President Trump on Oct. 1 signed a bill to keep the federal government running through Dec. 11. This “continuing resolution” (CR), which was approved by the House by a 359-57 vote and the Senate by a 84-10 vote, includes provisions to delay repayment by physicians of pandemic-related Medicare loans and to reduce the loans’ interest rate.
In an earlier news release, the American Medical Association reported that Congress and the White House had agreed to include the provisions on Medicare loans in the CR.
Under Medicare’s Accelerated and Advance Payments (AAP) Program, the Centers for Medicare & Medicaid Services (CMS) advanced funds to physicians who were financially impacted by the pandemic.
Revisions were made under the Coronavirus Aid, Relief, and Economic Security (CARES) Act to broaden the existing program to supply provider relief related to the public health emergency. The program was revised in March but suspended accepting new applications related to the pandemic in late April.
Physicians who received APP loans were required to begin repayment within 120 days after the loan disbursement. CMS planned to recoup the advances by offsetting them against Medicare claims payments due to physicians. Practices had up to 210 days (7 months) to repay the loans through this process before being asked to repay them directly with a 10.25 % interest rate.
For practices that received these advances, their Medicare cash flow was scheduled to dry up, starting in August. However, CMS quietly abstained from collecting these payments when they came due, according to Modern Healthcare.
New terms
Under the new loan repayment terms in the CR, repayment of the disbursed funds is postponed until 365 days after the date on which a practice received the money. The balance is due by September 2022.
The amount to be recouped from each claim is reduced from 100% to 25% of the claim for the first 11 months and to 50% of claims withheld for an additional 6 months. If the loan is not repaid in full by then, the provider must pay the balance with an interest rate of 4%.
More than 80% of the $100 billion that CMS loaned to health care providers through May 2 went to hospitals, Modern Healthcare calculated. Of the remainder, specialty or multispecialty practices received $3.5 billion, internal medicine specialists got $24 million, family physicians were loaned $15 million, and federally qualified health centers received $20 million.
In the AMA’s news release, AMA President Susan Bailey, MD, who assumed the post in June, called the original loan repayment plan an “economic sword hanging over physician practices.”
The American Gastroenterological Association has been advocating for more flexibility for the financial assistance programs, such as the Accelerated and Advanced Payment Program and the Paycheck Protection Program, that physicians have utilized. It is critical to give physicians leeway on these loans given that many practices are still not operating at full capacity.
Based on reporting from Medscape.com.
President Trump on Oct. 1 signed a bill to keep the federal government running through Dec. 11. This “continuing resolution” (CR), which was approved by the House by a 359-57 vote and the Senate by a 84-10 vote, includes provisions to delay repayment by physicians of pandemic-related Medicare loans and to reduce the loans’ interest rate.
In an earlier news release, the American Medical Association reported that Congress and the White House had agreed to include the provisions on Medicare loans in the CR.
Under Medicare’s Accelerated and Advance Payments (AAP) Program, the Centers for Medicare & Medicaid Services (CMS) advanced funds to physicians who were financially impacted by the pandemic.
Revisions were made under the Coronavirus Aid, Relief, and Economic Security (CARES) Act to broaden the existing program to supply provider relief related to the public health emergency. The program was revised in March but suspended accepting new applications related to the pandemic in late April.
Physicians who received APP loans were required to begin repayment within 120 days after the loan disbursement. CMS planned to recoup the advances by offsetting them against Medicare claims payments due to physicians. Practices had up to 210 days (7 months) to repay the loans through this process before being asked to repay them directly with a 10.25 % interest rate.
For practices that received these advances, their Medicare cash flow was scheduled to dry up, starting in August. However, CMS quietly abstained from collecting these payments when they came due, according to Modern Healthcare.
New terms
Under the new loan repayment terms in the CR, repayment of the disbursed funds is postponed until 365 days after the date on which a practice received the money. The balance is due by September 2022.
The amount to be recouped from each claim is reduced from 100% to 25% of the claim for the first 11 months and to 50% of claims withheld for an additional 6 months. If the loan is not repaid in full by then, the provider must pay the balance with an interest rate of 4%.
More than 80% of the $100 billion that CMS loaned to health care providers through May 2 went to hospitals, Modern Healthcare calculated. Of the remainder, specialty or multispecialty practices received $3.5 billion, internal medicine specialists got $24 million, family physicians were loaned $15 million, and federally qualified health centers received $20 million.
In the AMA’s news release, AMA President Susan Bailey, MD, who assumed the post in June, called the original loan repayment plan an “economic sword hanging over physician practices.”
The American Gastroenterological Association has been advocating for more flexibility for the financial assistance programs, such as the Accelerated and Advanced Payment Program and the Paycheck Protection Program, that physicians have utilized. It is critical to give physicians leeway on these loans given that many practices are still not operating at full capacity.
Based on reporting from Medscape.com.
President Trump on Oct. 1 signed a bill to keep the federal government running through Dec. 11. This “continuing resolution” (CR), which was approved by the House by a 359-57 vote and the Senate by a 84-10 vote, includes provisions to delay repayment by physicians of pandemic-related Medicare loans and to reduce the loans’ interest rate.
In an earlier news release, the American Medical Association reported that Congress and the White House had agreed to include the provisions on Medicare loans in the CR.
Under Medicare’s Accelerated and Advance Payments (AAP) Program, the Centers for Medicare & Medicaid Services (CMS) advanced funds to physicians who were financially impacted by the pandemic.
Revisions were made under the Coronavirus Aid, Relief, and Economic Security (CARES) Act to broaden the existing program to supply provider relief related to the public health emergency. The program was revised in March but suspended accepting new applications related to the pandemic in late April.
Physicians who received APP loans were required to begin repayment within 120 days after the loan disbursement. CMS planned to recoup the advances by offsetting them against Medicare claims payments due to physicians. Practices had up to 210 days (7 months) to repay the loans through this process before being asked to repay them directly with a 10.25 % interest rate.
For practices that received these advances, their Medicare cash flow was scheduled to dry up, starting in August. However, CMS quietly abstained from collecting these payments when they came due, according to Modern Healthcare.
New terms
Under the new loan repayment terms in the CR, repayment of the disbursed funds is postponed until 365 days after the date on which a practice received the money. The balance is due by September 2022.
The amount to be recouped from each claim is reduced from 100% to 25% of the claim for the first 11 months and to 50% of claims withheld for an additional 6 months. If the loan is not repaid in full by then, the provider must pay the balance with an interest rate of 4%.
More than 80% of the $100 billion that CMS loaned to health care providers through May 2 went to hospitals, Modern Healthcare calculated. Of the remainder, specialty or multispecialty practices received $3.5 billion, internal medicine specialists got $24 million, family physicians were loaned $15 million, and federally qualified health centers received $20 million.
In the AMA’s news release, AMA President Susan Bailey, MD, who assumed the post in June, called the original loan repayment plan an “economic sword hanging over physician practices.”
The American Gastroenterological Association has been advocating for more flexibility for the financial assistance programs, such as the Accelerated and Advanced Payment Program and the Paycheck Protection Program, that physicians have utilized. It is critical to give physicians leeway on these loans given that many practices are still not operating at full capacity.
Based on reporting from Medscape.com.
Cannabis may improve liver function in patients with obesity
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
FROM ACG 2020
Menstrual irregularity appears to be predictor of early death
than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.
In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.
Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.
During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
Irregular cycles appear to bring risks
After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.
Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.
Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.
The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m2); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%
vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).
Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.
Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.
Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.
Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
Expert suggests a probable underlying link
“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”
Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.
“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.
“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.
The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.
SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.
than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.
In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.
Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.
During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
Irregular cycles appear to bring risks
After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.
Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.
Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.
The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m2); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%
vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).
Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.
Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.
Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.
Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
Expert suggests a probable underlying link
“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”
Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.
“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.
“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.
The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.
SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.
than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.
In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.
Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.
During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
Irregular cycles appear to bring risks
After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.
Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.
Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.
The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m2); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%
vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).
Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.
Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.
Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.
Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
Expert suggests a probable underlying link
“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”
Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.
“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.
“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.
The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.
SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.
FROM THE BMJ
‘Tour de force’ study reveals therapeutic targets in 38% of cancer patients
The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.
The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.
Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.
“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.
“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
Relapsed/refractory vs. primary tumors
The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.
The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.
“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
Multiple alterations and resistance
The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.
“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.
“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”
The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.
“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
Actionable mutations make a difference
Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.
“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.
“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”
From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.
“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”
Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”
Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”
Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.
NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.
SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.
The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.
The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.
Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.
“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.
“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
Relapsed/refractory vs. primary tumors
The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.
The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.
“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
Multiple alterations and resistance
The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.
“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.
“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”
The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.
“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
Actionable mutations make a difference
Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.
“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.
“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”
From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.
“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”
Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”
Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”
Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.
NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.
SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.
The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.
The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.
Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.
“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.
“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
Relapsed/refractory vs. primary tumors
The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.
The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.
“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
Multiple alterations and resistance
The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.
“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.
“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”
The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.
“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
Actionable mutations make a difference
Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.
“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.
“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”
From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.
“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”
Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”
Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”
Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.
NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.
SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
POP surgeries not tied to decreased sexual functioning
Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.
In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.
“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.*
POP surgeries positively impact sexual function, dyspareunia outcomes
The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.
Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.
Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.
The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
Menopausal status and other considerations
Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”
The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.
It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
Study provides preoperative counseling help
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”
In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).”
Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”
Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery. 
“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”
The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.
*This article was updated on 10/28.
Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.
In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.
“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.*
POP surgeries positively impact sexual function, dyspareunia outcomes
The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.
Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.
Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.
The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
Menopausal status and other considerations
Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”
The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.
It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
Study provides preoperative counseling help
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”
In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).”
Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”
Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery.
“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”
The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.
*This article was updated on 10/28.
Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.
In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.
“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.*
POP surgeries positively impact sexual function, dyspareunia outcomes
The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.
Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.
Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.
The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
Menopausal status and other considerations
Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”
The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.
It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
Study provides preoperative counseling help
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”
In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).”
Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”
Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery.
“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”
The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.
*This article was updated on 10/28.
FROM OBSTETRICS & GYNECOLOGY
COVID-19: Thromboembolic events high despite prophylaxis
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.
in a new large observational U.S. study.
“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview.
“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.
However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.
The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
Rates similar to other very sick patients
The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.
“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”
He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”
Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.
“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.
“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.
The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.
“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”
For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White.
Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.
Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.
Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.
Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.
“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.
“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”
Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.
“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
ARDS biggest risk factor
Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.
“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”
They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.
“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.
“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.
The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
Wait for randomized trials
In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.
Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.
“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”
He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.
“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.
This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.
A version of this article originally appeared on Medscape.com.