Tara Haelle

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.

For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.

MarianVejcik/Getty Images

Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.

“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”

The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.

The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.

“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”

For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:

• Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
• For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
• Patients younger than 65 should receive the pneumococcal vaccine.
• Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.

The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.

The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.

“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.

Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”

“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”

For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.

Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.

Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.

For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.

For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.

For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.

To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.

“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”

Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.

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

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

A simple blood test that looks for a combination of specific RNA snippets may become a novel way to screen for early-onset colorectal cancer, suggests a new study published online in Gastroenterology.

Researchers identified four microRNAs that together comprise a signature biomarker that can be used to detect and diagnose the presence of colorectal cancer from a liquid biopsy in a younger population.

MicroRNAs, or miRNAs, are small RNA molecules that do not encode proteins but are used instead to regulate gene expression. The study authors developed and validated a panel that detects four miRNAs occurring at higher levels in plasma samples from patients with early-onset colorectal cancer, with high sensitivity and specificity.

“The point would be to use this test as a routine part of annual healthcare, or for people in high-risk families every 6 months,” study senior author Ajay Goel, PhD, MS, chair of the department of molecular diagnostics and experimental therapeutics at the City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

“It’s affordable, it can be done easily from a small tube of blood, and as long as that test stays negative, you’re good,” Dr. Goel said, because even if patients miss a test, the next one, whether it’s 6 months or a year later, will catch any potential cancer.

“Colon cancer is not going to kill somebody overnight, so this should be used as a precursor to colonoscopy. As long as that test is negative, you can postpone a colonoscopy,” he said.

Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital, both in Boston, who was not involved in the research, said in an interview that the findings are exciting.

“It would be really value-added to have a blood-based screening test,” Dr. Chan said, adding that researchers have pursued multiple different avenues in pursuit of one. “It’s very nice to see that area progress and to actually have some evidence that microRNAs could be a potential biomarker for colorectal cancer.”
 

Screening now insufficient for early-onset disease

The U.S. Preventive Services Task Force recently lowered the recommended age to 45 years to begin screening for colorectal cancer. Part of the rationale for the change came from the rising rates of early-onset colorectal cancer, a distinct clinical and molecular entity that tends to have poorer survival than late-onset disease, the authors noted.

Early-onset disease, occurring primarily in people under 50 without a family or genetic history of colorectal cancer, now makes up about 10%-15% of all new cases and continues to rise, they write.

“Early-onset colorectal cancer patients are more likely to exhibit an advanced stage tumor at initial presentation, distal tumor localization, signet ring histology, and a disease presentation with concurrent metastasis,” the authors wrote. “This raises the logistical clinical concern that, since the tumors in early-onset colorectal cancer patients are often more aggressive than those with late-onset colorectal cancer, a delayed diagnosis could have a significant adverse impact and can lead to early death.”

Yet current screening strategies are insufficient for detecting enough early-onset cases, the authors assert.

Colonoscopies are invasive, carry a risk for complications, and are cost- and time-prohibitive for people at average risk. Meanwhile, existing fecal and blood tests “lack adequate diagnostic performance for the early detection of colorectal cancer, especially early-onset colorectal cancer, as these assays have yet to be explored or developed in this population,” they wrote.

The ideal “diagnostic modality should preferably be acceptable to healthy individuals, inexpensive, rapid, and preferably noninvasive,” they note.
 

Finding and validating miRNA

The researchers therefore turned to the concept of a liquid biopsy, focusing on identifying miRNAs associated with colorectal cancer, because their expression tends to be stable in tissues, blood, stool, and other body fluids.

They first analyzed an miRNA expression profiling dataset from 1,061 individuals to look for miRNAs whose expression was higher in colorectal cancer patients. The dataset included 42 patients with stage 1-2 early-onset colorectal cancer, 370 patients with stage 1-2 late-onset colorectal cancer, 62 patients younger than 50 years without cancer, and 587 patients aged 50 years or older without cancer.

The researchers found 28 miRNAs that were significantly unregulated in early-onset colorectal cancer tissue samples, compared with cancer-free samples and 11 miRNAs unregulated specifically in only the early-onset colorectal cancer samples. Four of these 11 miRNAs were adequately distinct from one another and were detectable in the plasma samples that the researchers would use to train and validate them as a combination biomarker.

The researchers used 117 plasma samples from Japan, including 72 from people with early-onset colorectal cancer and 45 from healthy donors, to develop and train an assay detecting the four miRNAs. They then validated the assay using 142 plasma samples from Spain, including 77 with early-onset colorectal cancer and 65 healthy donors.

In the Japan cohort, the four-miRNA assay had a sensitivity of 90% and a specificity of 80%, with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 84%. In the Spain cohort used for validation, the assay performed with a sensitivity of 82%, a specificity of 86%, a PPV of 88%, and an NPV of 80%.

“Taken together, the genome-wide transcriptomic profiling approach was indeed robust, as it identified the biomarkers that were successfully trained and validated in plasma specimens from independent cohorts of patients with early-onset colorectal cancer, hence highlighting their translational potential in the clinic for the detection of this malignancy in early stages,” the authors wrote.

By disease stage, the four-miRNA panel identified both early-stage (stage 1-2; sensitivity, 92%; specificity, 80%) and late-stage (stage 3-4; sensitivity, 79%; specificity, 86%) early-onset colorectal cancer in the validation cohort.
 

Clinical benefit of blood test

The researchers also assessed the benefit-harm trade-off of this liquid biopsy assay compared with other screening modalities, taking into consideration the risk for false positives and false negatives.

A decision curve analysis “revealed that the miRNA panel achieved a higher net benefit regardless of threshold probability in comparison to intervention for all patients or none of the patients,” the researchers reported. “These findings suggest that this miRNA panel might offer more clinical benefit with regards to the avoidance of physical harm and misdiagnosis.”

They also found that expression levels of these four miRNAs significantly decreased after surgical removal of the colorectal cancer, strongly suggesting that the miRNAs do originate with the tumor.

“To have a relatively inexpensive and noninvasive means of screening a younger population is a very important unmet need,” said Dr. Chan.

It’s not feasible to recommend colonoscopies in people younger than 45 years because of resource constraints, he said, so “this is a wonderful new development to actually have the possibility of a blood-based screening test for younger individuals, especially given that rising incidence of young-onset colorectal cancer.”

Dr. Goel pointed out that only half of those recommended to get screened for colorectal cancer actually undergo screening, and a large reason for that is the desire to avoid colonoscopy, a concern echoed in the findings of a recent study by Christopher V. Almario, MD, MSHPM, and colleagues.

Dr. Goel expects that this strategy would increase compliance with screening because it’s less invasive and more affordable, particularly for younger patients. He estimates that a commercial assay using this panel, if approved by the Food and Drug Administration, should cost less than $100.

Dr. Almario, an assistant professor of medicine at the Cedars-Sinai Karsh Division of Gastroenterology and Hepatology in Los Angeles, agreed that an FDA-approved blood-based screening test would be a “game-changer,” as long as it’s accurate and effective.

Though Dr. Almario did not review the data in Goel’s study, he said in an interview that a blood test for colorectal cancer screening would be “the holy grail, so to speak, in terms of really moving the needle on screening uptake.”
 

Next steps

Dr. Chan noted that one caveat to consider with this study is that it was done in a relatively small population of individuals, even though the test was validated in a second set of plasma samples.

“Additional validation needs to be done in larger numbers of patients to really understand the performance characteristics because it is possible that some of these signatures may, when they’re using a broader group of individuals, not perform as well,” Dr. Chan said.

Dr. Goel said he is working with several companies right now to develop and further test a commercial product. He anticipates it may be shelf-ready in 2-5 years.

“The take-home message is that clinicians need to be more cognizant of the fact that incidence of this disease is rising, and we need to do something about it,” Dr. Goel said, particularly for those younger than 45 years who currently don’t have a screening option.

“Now we have at least a sliver of hope for those who might be suffering from this disease, for those for whom we have zero screening or diagnostic tests,” he said.

The research was funded by the National Cancer Institute and Fundación MAPFRE Guanarteme. Dr. Goel, Dr. Chan, and Dr. Almario reported no conflicts of interest.

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

A simple blood test that looks for a combination of specific RNA snippets may become a novel way to screen for early-onset colorectal cancer, suggests a new study published online in Gastroenterology.

Researchers identified four microRNAs that together comprise a signature biomarker that can be used to detect and diagnose the presence of colorectal cancer from a liquid biopsy in a younger population.

MicroRNAs, or miRNAs, are small RNA molecules that do not encode proteins but are used instead to regulate gene expression. The study authors developed and validated a panel that detects four miRNAs occurring at higher levels in plasma samples from patients with early-onset colorectal cancer, with high sensitivity and specificity.

“The point would be to use this test as a routine part of annual healthcare, or for people in high-risk families every 6 months,” study senior author Ajay Goel, PhD, MS, chair of the department of molecular diagnostics and experimental therapeutics at the City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

“It’s affordable, it can be done easily from a small tube of blood, and as long as that test stays negative, you’re good,” Dr. Goel said, because even if patients miss a test, the next one, whether it’s 6 months or a year later, will catch any potential cancer.

“Colon cancer is not going to kill somebody overnight, so this should be used as a precursor to colonoscopy. As long as that test is negative, you can postpone a colonoscopy,” he said.

Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital, both in Boston, who was not involved in the research, said in an interview that the findings are exciting.

“It would be really value-added to have a blood-based screening test,” Dr. Chan said, adding that researchers have pursued multiple different avenues in pursuit of one. “It’s very nice to see that area progress and to actually have some evidence that microRNAs could be a potential biomarker for colorectal cancer.”
 

Screening now insufficient for early-onset disease

The U.S. Preventive Services Task Force recently lowered the recommended age to 45 years to begin screening for colorectal cancer. Part of the rationale for the change came from the rising rates of early-onset colorectal cancer, a distinct clinical and molecular entity that tends to have poorer survival than late-onset disease, the authors noted.

Early-onset disease, occurring primarily in people under 50 without a family or genetic history of colorectal cancer, now makes up about 10%-15% of all new cases and continues to rise, they write.

“Early-onset colorectal cancer patients are more likely to exhibit an advanced stage tumor at initial presentation, distal tumor localization, signet ring histology, and a disease presentation with concurrent metastasis,” the authors wrote. “This raises the logistical clinical concern that, since the tumors in early-onset colorectal cancer patients are often more aggressive than those with late-onset colorectal cancer, a delayed diagnosis could have a significant adverse impact and can lead to early death.”

Yet current screening strategies are insufficient for detecting enough early-onset cases, the authors assert.

Colonoscopies are invasive, carry a risk for complications, and are cost- and time-prohibitive for people at average risk. Meanwhile, existing fecal and blood tests “lack adequate diagnostic performance for the early detection of colorectal cancer, especially early-onset colorectal cancer, as these assays have yet to be explored or developed in this population,” they wrote.

The ideal “diagnostic modality should preferably be acceptable to healthy individuals, inexpensive, rapid, and preferably noninvasive,” they note.
 

Finding and validating miRNA

The researchers therefore turned to the concept of a liquid biopsy, focusing on identifying miRNAs associated with colorectal cancer, because their expression tends to be stable in tissues, blood, stool, and other body fluids.

They first analyzed an miRNA expression profiling dataset from 1,061 individuals to look for miRNAs whose expression was higher in colorectal cancer patients. The dataset included 42 patients with stage 1-2 early-onset colorectal cancer, 370 patients with stage 1-2 late-onset colorectal cancer, 62 patients younger than 50 years without cancer, and 587 patients aged 50 years or older without cancer.

The researchers found 28 miRNAs that were significantly unregulated in early-onset colorectal cancer tissue samples, compared with cancer-free samples and 11 miRNAs unregulated specifically in only the early-onset colorectal cancer samples. Four of these 11 miRNAs were adequately distinct from one another and were detectable in the plasma samples that the researchers would use to train and validate them as a combination biomarker.

The researchers used 117 plasma samples from Japan, including 72 from people with early-onset colorectal cancer and 45 from healthy donors, to develop and train an assay detecting the four miRNAs. They then validated the assay using 142 plasma samples from Spain, including 77 with early-onset colorectal cancer and 65 healthy donors.

In the Japan cohort, the four-miRNA assay had a sensitivity of 90% and a specificity of 80%, with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 84%. In the Spain cohort used for validation, the assay performed with a sensitivity of 82%, a specificity of 86%, a PPV of 88%, and an NPV of 80%.

“Taken together, the genome-wide transcriptomic profiling approach was indeed robust, as it identified the biomarkers that were successfully trained and validated in plasma specimens from independent cohorts of patients with early-onset colorectal cancer, hence highlighting their translational potential in the clinic for the detection of this malignancy in early stages,” the authors wrote.

By disease stage, the four-miRNA panel identified both early-stage (stage 1-2; sensitivity, 92%; specificity, 80%) and late-stage (stage 3-4; sensitivity, 79%; specificity, 86%) early-onset colorectal cancer in the validation cohort.
 

Clinical benefit of blood test

The researchers also assessed the benefit-harm trade-off of this liquid biopsy assay compared with other screening modalities, taking into consideration the risk for false positives and false negatives.

A decision curve analysis “revealed that the miRNA panel achieved a higher net benefit regardless of threshold probability in comparison to intervention for all patients or none of the patients,” the researchers reported. “These findings suggest that this miRNA panel might offer more clinical benefit with regards to the avoidance of physical harm and misdiagnosis.”

They also found that expression levels of these four miRNAs significantly decreased after surgical removal of the colorectal cancer, strongly suggesting that the miRNAs do originate with the tumor.

“To have a relatively inexpensive and noninvasive means of screening a younger population is a very important unmet need,” said Dr. Chan.

It’s not feasible to recommend colonoscopies in people younger than 45 years because of resource constraints, he said, so “this is a wonderful new development to actually have the possibility of a blood-based screening test for younger individuals, especially given that rising incidence of young-onset colorectal cancer.”

Dr. Goel pointed out that only half of those recommended to get screened for colorectal cancer actually undergo screening, and a large reason for that is the desire to avoid colonoscopy, a concern echoed in the findings of a recent study by Christopher V. Almario, MD, MSHPM, and colleagues.

Dr. Goel expects that this strategy would increase compliance with screening because it’s less invasive and more affordable, particularly for younger patients. He estimates that a commercial assay using this panel, if approved by the Food and Drug Administration, should cost less than $100.

Dr. Almario, an assistant professor of medicine at the Cedars-Sinai Karsh Division of Gastroenterology and Hepatology in Los Angeles, agreed that an FDA-approved blood-based screening test would be a “game-changer,” as long as it’s accurate and effective.

Though Dr. Almario did not review the data in Goel’s study, he said in an interview that a blood test for colorectal cancer screening would be “the holy grail, so to speak, in terms of really moving the needle on screening uptake.”
 

Next steps

Dr. Chan noted that one caveat to consider with this study is that it was done in a relatively small population of individuals, even though the test was validated in a second set of plasma samples.

“Additional validation needs to be done in larger numbers of patients to really understand the performance characteristics because it is possible that some of these signatures may, when they’re using a broader group of individuals, not perform as well,” Dr. Chan said.

Dr. Goel said he is working with several companies right now to develop and further test a commercial product. He anticipates it may be shelf-ready in 2-5 years.

“The take-home message is that clinicians need to be more cognizant of the fact that incidence of this disease is rising, and we need to do something about it,” Dr. Goel said, particularly for those younger than 45 years who currently don’t have a screening option.

“Now we have at least a sliver of hope for those who might be suffering from this disease, for those for whom we have zero screening or diagnostic tests,” he said.

The research was funded by the National Cancer Institute and Fundación MAPFRE Guanarteme. Dr. Goel, Dr. Chan, and Dr. Almario reported no conflicts of interest.

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

A simple blood test that looks for a combination of specific RNA snippets may become a novel way to screen for early-onset colorectal cancer, suggests a new study published online in Gastroenterology.

Researchers identified four microRNAs that together comprise a signature biomarker that can be used to detect and diagnose the presence of colorectal cancer from a liquid biopsy in a younger population.

MicroRNAs, or miRNAs, are small RNA molecules that do not encode proteins but are used instead to regulate gene expression. The study authors developed and validated a panel that detects four miRNAs occurring at higher levels in plasma samples from patients with early-onset colorectal cancer, with high sensitivity and specificity.

“The point would be to use this test as a routine part of annual healthcare, or for people in high-risk families every 6 months,” study senior author Ajay Goel, PhD, MS, chair of the department of molecular diagnostics and experimental therapeutics at the City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

“It’s affordable, it can be done easily from a small tube of blood, and as long as that test stays negative, you’re good,” Dr. Goel said, because even if patients miss a test, the next one, whether it’s 6 months or a year later, will catch any potential cancer.

“Colon cancer is not going to kill somebody overnight, so this should be used as a precursor to colonoscopy. As long as that test is negative, you can postpone a colonoscopy,” he said.

Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital, both in Boston, who was not involved in the research, said in an interview that the findings are exciting.

“It would be really value-added to have a blood-based screening test,” Dr. Chan said, adding that researchers have pursued multiple different avenues in pursuit of one. “It’s very nice to see that area progress and to actually have some evidence that microRNAs could be a potential biomarker for colorectal cancer.”
 

Screening now insufficient for early-onset disease

The U.S. Preventive Services Task Force recently lowered the recommended age to 45 years to begin screening for colorectal cancer. Part of the rationale for the change came from the rising rates of early-onset colorectal cancer, a distinct clinical and molecular entity that tends to have poorer survival than late-onset disease, the authors noted.

Early-onset disease, occurring primarily in people under 50 without a family or genetic history of colorectal cancer, now makes up about 10%-15% of all new cases and continues to rise, they write.

“Early-onset colorectal cancer patients are more likely to exhibit an advanced stage tumor at initial presentation, distal tumor localization, signet ring histology, and a disease presentation with concurrent metastasis,” the authors wrote. “This raises the logistical clinical concern that, since the tumors in early-onset colorectal cancer patients are often more aggressive than those with late-onset colorectal cancer, a delayed diagnosis could have a significant adverse impact and can lead to early death.”

Yet current screening strategies are insufficient for detecting enough early-onset cases, the authors assert.

Colonoscopies are invasive, carry a risk for complications, and are cost- and time-prohibitive for people at average risk. Meanwhile, existing fecal and blood tests “lack adequate diagnostic performance for the early detection of colorectal cancer, especially early-onset colorectal cancer, as these assays have yet to be explored or developed in this population,” they wrote.

The ideal “diagnostic modality should preferably be acceptable to healthy individuals, inexpensive, rapid, and preferably noninvasive,” they note.
 

Finding and validating miRNA

The researchers therefore turned to the concept of a liquid biopsy, focusing on identifying miRNAs associated with colorectal cancer, because their expression tends to be stable in tissues, blood, stool, and other body fluids.

They first analyzed an miRNA expression profiling dataset from 1,061 individuals to look for miRNAs whose expression was higher in colorectal cancer patients. The dataset included 42 patients with stage 1-2 early-onset colorectal cancer, 370 patients with stage 1-2 late-onset colorectal cancer, 62 patients younger than 50 years without cancer, and 587 patients aged 50 years or older without cancer.

The researchers found 28 miRNAs that were significantly unregulated in early-onset colorectal cancer tissue samples, compared with cancer-free samples and 11 miRNAs unregulated specifically in only the early-onset colorectal cancer samples. Four of these 11 miRNAs were adequately distinct from one another and were detectable in the plasma samples that the researchers would use to train and validate them as a combination biomarker.

The researchers used 117 plasma samples from Japan, including 72 from people with early-onset colorectal cancer and 45 from healthy donors, to develop and train an assay detecting the four miRNAs. They then validated the assay using 142 plasma samples from Spain, including 77 with early-onset colorectal cancer and 65 healthy donors.

In the Japan cohort, the four-miRNA assay had a sensitivity of 90% and a specificity of 80%, with a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 84%. In the Spain cohort used for validation, the assay performed with a sensitivity of 82%, a specificity of 86%, a PPV of 88%, and an NPV of 80%.

“Taken together, the genome-wide transcriptomic profiling approach was indeed robust, as it identified the biomarkers that were successfully trained and validated in plasma specimens from independent cohorts of patients with early-onset colorectal cancer, hence highlighting their translational potential in the clinic for the detection of this malignancy in early stages,” the authors wrote.

By disease stage, the four-miRNA panel identified both early-stage (stage 1-2; sensitivity, 92%; specificity, 80%) and late-stage (stage 3-4; sensitivity, 79%; specificity, 86%) early-onset colorectal cancer in the validation cohort.
 

Clinical benefit of blood test

The researchers also assessed the benefit-harm trade-off of this liquid biopsy assay compared with other screening modalities, taking into consideration the risk for false positives and false negatives.

A decision curve analysis “revealed that the miRNA panel achieved a higher net benefit regardless of threshold probability in comparison to intervention for all patients or none of the patients,” the researchers reported. “These findings suggest that this miRNA panel might offer more clinical benefit with regards to the avoidance of physical harm and misdiagnosis.”

They also found that expression levels of these four miRNAs significantly decreased after surgical removal of the colorectal cancer, strongly suggesting that the miRNAs do originate with the tumor.

“To have a relatively inexpensive and noninvasive means of screening a younger population is a very important unmet need,” said Dr. Chan.

It’s not feasible to recommend colonoscopies in people younger than 45 years because of resource constraints, he said, so “this is a wonderful new development to actually have the possibility of a blood-based screening test for younger individuals, especially given that rising incidence of young-onset colorectal cancer.”

Dr. Goel pointed out that only half of those recommended to get screened for colorectal cancer actually undergo screening, and a large reason for that is the desire to avoid colonoscopy, a concern echoed in the findings of a recent study by Christopher V. Almario, MD, MSHPM, and colleagues.

Dr. Goel expects that this strategy would increase compliance with screening because it’s less invasive and more affordable, particularly for younger patients. He estimates that a commercial assay using this panel, if approved by the Food and Drug Administration, should cost less than $100.

Dr. Almario, an assistant professor of medicine at the Cedars-Sinai Karsh Division of Gastroenterology and Hepatology in Los Angeles, agreed that an FDA-approved blood-based screening test would be a “game-changer,” as long as it’s accurate and effective.

Though Dr. Almario did not review the data in Goel’s study, he said in an interview that a blood test for colorectal cancer screening would be “the holy grail, so to speak, in terms of really moving the needle on screening uptake.”
 

Next steps

Dr. Chan noted that one caveat to consider with this study is that it was done in a relatively small population of individuals, even though the test was validated in a second set of plasma samples.

“Additional validation needs to be done in larger numbers of patients to really understand the performance characteristics because it is possible that some of these signatures may, when they’re using a broader group of individuals, not perform as well,” Dr. Chan said.

Dr. Goel said he is working with several companies right now to develop and further test a commercial product. He anticipates it may be shelf-ready in 2-5 years.

“The take-home message is that clinicians need to be more cognizant of the fact that incidence of this disease is rising, and we need to do something about it,” Dr. Goel said, particularly for those younger than 45 years who currently don’t have a screening option.

“Now we have at least a sliver of hope for those who might be suffering from this disease, for those for whom we have zero screening or diagnostic tests,” he said.

The research was funded by the National Cancer Institute and Fundación MAPFRE Guanarteme. Dr. Goel, Dr. Chan, and Dr. Almario reported no conflicts of interest.

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

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

"When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory panel with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

This article was updated on Aug. 18, 2022.

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

"When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory panel with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

This article was updated on Aug. 18, 2022.

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

"When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory panel with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

This article was updated on Aug. 18, 2022.

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

”When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory board with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

”When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory board with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Patients said they’d prefer fecal immunochemical test (FIT)–fecal DNA tests over any of the other colorectal cancer screening (CRC) modalities currently recommended by the U.S. Multi-Society Task Force, according to a study published in Clinical Gastroenterology and Hepatology.

Just over a third of American adults aged 40 and older who hadn’t yet been screened for CRC preferred the FIT–fecal DNA test every 3 years, whereas just one in seven respondents preferred a colonoscopy – considered the gold standard in colorectal cancer screening – every 10 years.

”When you talk to patients and to your friends and family members, people tend to think colonoscopy is synonymous with colon cancer screening, but we have lots of different tests,” senior author Christopher V. Almario, MD, MSHPM, of the department of medicine at the Karsh division of gastroenterology and hepatology, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Most people in general tend to prefer noninvasive stool tests, and when we try to predict who would prefer what, we actually couldn’t, so this is a very personal decision,” Dr. Almario said. “It’s important for clinicians to offer multiple choices to their patients, not to mention just colonoscopy. We have data from observing clinician-patient interactions showing that, a lot of times, colonoscopy is the only test that’s offered, despite there being multiple options.”

At the very least, Dr. Almario said, providers should offer patients a colonoscopy along with a noninvasive test, particularly a stool test, and discuss the two options, getting the patient’s input in terms of what they prefer. “The best test is the test that actually gets done,” he said.
 

Offering patients options

Reid M. Ness, MD, MPH, an associate professor of medicine in the division of gastroenterology, hepatology and nutrition at Vanderbilt University Medical Center in Nashville, was not involved with the study but wasn’t surprised at the findings since “most people wisely prefer to avoid invasive procedures,” he said in an interview. He agreed that many patients aren’t necessarily informed of all their options for screening.

“Many people who are now being offered colonoscopy as their only screening option may prefer a noninvasive option, such as FIT or multitarget stool DNA testing,” Dr. Ness said. “Also, people now refusing colonoscopy for colorectal cancer screening may instead accept FIT or multitarget stool DNA testing. It is difficult to know how many people now refusing colorectal cancer screening may have accepted screening if it had been offered differently.”

That’s precisely what Dr. Almario and his colleagues wanted to find out. They surveyed 1,000 people aged 40 and older who were at average risk for colorectal cancer to find out their preferences for different screening modalities and what features of different screening types they most valued. The researchers asked about the following screening tests recommended by the U.S. Multi-Society Task Force:

• FIT every year.
• FIT–fecal DNA every 3 years.
• Colon video capsule every 5 years.
• CT colonography every 5 years.
• Colonoscopy every 10 years.

The respondents who completed the online survey were recruited from a sample of more than 20 million people across the United States who have agreed to receive survey invitations. Respondents were excluded if they had a first-degree relative with colorectal cancer, had already undergone colorectal cancer screening or had been diagnosed with colon polyps, Crohn’s disease, or ulcerative colitis.

The respondents were split into those aged 40-49 (61% of the sample) who had not yet discussed colorectal cancer screening with their providers and those aged 50 and older, who might have already discussed it and declined. Eighty percent of the respondents were White, 6% were Black, 6% were Hispanic, 4% were Asian, and 3% reported another race/ethnicity. Just over half (52%) had at least two comorbidities. A quarter (25%) reported one comorbidity, and 22% reported none.



In thinking about the decision to get screened, respondents ranked the test type as the most important consideration, followed by the reduction in their chance of developing colorectal cancer and then frequency of the test. Lower priority on the list of considerations were their chances of a complication, bowel prep before the test, and required diet changes before the test.

The test preferred by the highest proportion of respondents was the FIT–fecal DNA test every 3 years, preferred by 35% of respondents, followed by the colon capsule video test every 5 years (28%). About one in seven respondents (14%) preferred a colonoscopy every 10 years, followed by the annual FIT (12%) and CT colonography every 5 years (11%). When limited only to the two tier 1–option tests – the annual FIT or a colonoscopy every 10 years – a substantial majority of the younger (69%) and older (77%) groups preferred the annual FIT.

”This finding is discordant with current CRC screening utilization in the United States where colonoscopy is the most commonly performed test, and this may partially explain our suboptimal screening rates,” the authors wrote. “Our findings suggest that screening programs should strongly consider a sequential-based strategy where FIT is offered first, and if declined then colonoscopy.”
 

Underlying factors

Dr. Ness said that many primary care providers might prefer to offer colonoscopies instead of annual FIT tests because it’s easier to track a test given every 10 years instead of every year or every 3 years.

“Providers across most of the U.S. are incentivized to recommend colonoscopy as the primary screening modality because the burden of follow-up on them is less,” Dr. Ness said. “They are able to justify this choice given colonoscopy remains the most accurate screening modality.”

Dr. Ness pointed to the programmatic screening program at Kaiser Permanente of Northern California health care system as a model for a program that utilizes FIT tests more often.

“The only way to accomplish an efficient and equitable colorectal cancer screening program is within the context of a national health service or plan,” Dr. Ness added. “Otherwise, the uninsured and underinsured will remain excluded from the benefits of colorectal cancer screening.”

Preferences did not differ a great deal between the age groups, with 35% of the younger group and 37% of the older group both preferring the FIT–fecal DNA tests every 3 years. Slightly more people in the 50+ age group preferred an annual fit (19% vs. 12%) as opposed to the colon capsule video every 5 years (28% of younger group vs. 23%) or colon CT scan every 5 years (11% of younger group vs. 8%), but the differences were statistically significant (P = .019).

In fact, “sociodemographic, clinical characteristics, and colorectal cancer screening knowledge, attitudes, and beliefs were not predictive of selecting FIT or colonoscopy,” the authors found. ”This demonstrates the individualized nature of decision making on colorectal cancer screening tests. Moreover, as most individuals preferred FIT, it again emphasizes the importance of sequential or choice-based strategies for colorectal cancer screening.”

However, one of the study’s notable limitations was its high proportion of White patients relative to other racial/ethnic groups, so additional research may illuminate whether different sociodemographic groups do have slight preferences for one test over another, Dr. Almario said. The advantage to colonoscopies, he noted, is that they only occur every 10 years and if polyps are discovered, they can be taken care of right away.

”You don’t have to think about it for a decade, which is certainly a pro for the colonoscopy,” Dr. Almario said. “The FIT test is obviously less invasive, but you have to do it every year for it to be an effective screening test.” He noted that some data have shown a drop-off in compliance over multiple years. “We certainly need more systems in place to remind patients and providers to do it annually so that we can see the ultimate screening benefit from doing that test specifically.”

“The most important point from the clinical perspective is, when we’re talking to patients about colon cancer screening, make sure to give them a choice,” Dr. Almario said. “We just can’t look at someone’s chart, their clinical characteristics or demographics, and predict what tests they would prefer. We need to ask them. We need to present them with the options, go over the pros and cons of colonoscopy, the pros and cons of the stool test, and ask the patient what they would prefer to do.”

The research was funded by the National Cancer Institute and the National Institutes of Health. One author served on an advisory board with Exact Sciences. The other authors and Dr. Ness had no disclosures.

Marital status is a relevant risk factor in considering the prognosis of patients with gastric cancer, according to research published in the Journal of Investigative Medicine.

Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.

“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”

The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.

“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
 

Exploring the marital status–cancer survival connection

Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.

Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”

In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.

Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.

Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.

Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.

“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
 

What long-term relationships reveal

These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.

“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.

If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”

Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.

Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.

Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.

A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.

“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.

“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.

“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”

The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.

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

Marital status is a relevant risk factor in considering the prognosis of patients with gastric cancer, according to research published in the Journal of Investigative Medicine.

Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.

“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”

The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.

“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
 

Exploring the marital status–cancer survival connection

Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.

Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”

In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.

Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.

Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.

Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.

“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
 

What long-term relationships reveal

These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.

“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.

If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”

Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.

Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.

Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.

A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.

“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.

“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.

“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”

The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.

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

Marital status is a relevant risk factor in considering the prognosis of patients with gastric cancer, according to research published in the Journal of Investigative Medicine.

Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.

“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”

The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.

“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
 

Exploring the marital status–cancer survival connection

Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.

Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”

In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.

Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.

Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.

Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.

“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
 

What long-term relationships reveal

These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.

“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.

If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”

Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.

Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.

Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.

A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.

“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.

“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.

“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”

The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.

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

Adults younger than 55 years were least likely to get screened for colorectal cancer over the past 2 decades, particularly if they were Hispanic or Asian or had a low income, lower education level, or no health insurance, according to a new study published online in Cancer Epidemiology, Biomarkers & Prevention.

The findings have raised concerns that disparities in screening rates will be even greater in adults aged 45-49 years, prompting the need for increased awareness and outreach to ensure that underserved groups have access to screenings.

“Differences in prevalence of screening by race and ethnicity, educational attainment, household income, and health insurance were most pronounced for those ages 50-54 years, whereas older adults experienced larger increases in prevalence across these groups,” wrote Po-Hong Liu, MD, MPH, a clinical investigator at Harvard University, Boston, and his colleagues. “The persistent and worsening disparities we observed in adults 50-54 years may extend to those ages 45-49 as they become eligible for screening.”

The U.S. Preventive Services Task Force shifted their recommendation for colorectal cancer screening in May 2021 to 5 years earlier, advising people to start screenings at 45 instead of 50, which aligns with the recommendations the American Cancer Society made 3 years earlier.

Both organizations made the change because of increasing rates of colorectal cancer in adults under age 50 and research indicating that beginning screenings at age 45 results in fewer cases, fewer deaths, and more life years gained.

“Across all age groups, colorectal cancer screening participation remains below national goals, and the benefits of screening are not equally realized across populations,” senior author Caitlin Murphy, PhD, MPH, associate professor, UTHealth School of Public Health, Houston, said in a prepared statement. “Extra care must be taken to ensure that expanding screening to younger ages does not negatively impact efforts to eliminate disparities in colorectal screening and outcomes nor jeopardize efforts to increase screening initiation among older adults who remain unscreened.”
 

Data analyzed from 8 years over 2 decades

The researchers analyzed data from the CDC’s cross-sectional National Health Interview Survey during 8 years over the past 2 decades: 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018.

The number of participants each year ranged from a low of 21,781 in 2008 to a high of 34,557 in 2013. After excluding participants with a history of colorectal cancer or missing information on screenings, the total population sample included 80,220 participants 50-75 years old.

The researchers considered a person as having been screened if they received at least one recommended screening test within the year covered by the survey, regardless of why they underwent the test.

Recommended tests included sigmoidoscopy, colonoscopy, and stool-based tests for all survey years. In addition, the surveys for 2010, 2015, and 2018 included CT colonography, and the 2018 survey included FIT-DNA.
 

Screening across population groups

Colorectal cancer screening rates have doubled in the past 2 decades, from 36.7% in 2000 to 66.1% in 2018.

Rates are considerably lower, however, for several key groups, including the youngest group. Less than half (47.6%) of those aged 50-54 years received screenings in 2018, though this was still a nearly 20-point improvement over the 28.2% in this age group who were screened in 2000.

Separate from age, several other groups continue to have low screening rates in general, including Hispanics (56.5%, up from 25.9% in 2000), Asians (57.1%, up from 22.6% in 2000), those who have not received a high school degree (53.6%, up from 26.8% in 2000), and those from low income families (56.6%, up from 30.2% in 2000).

The group with the greatest need for more outreach and screenings are people without insurance, only 39.7% of whom were screened in 2018, a modest increase from 30.2% in 2000.

The biggest increase in screenings over time occurred in those aged 70-75 years, from 46.4% in 2000 to 78% in 2018 overall.

Racial/ethnic, economic, education, and insurance-based disparities were particularly evident the younger people were, including in terms of progress made over time.

For example, screenings of non-Hispanic White people aged 50-54 years improved 21 points (30.3% to 51%) between 2000 and 2018, compared with 19 points in Hispanics (16.7% to 35.5%) and 15 points in Asians (17.3% to 32.3%). Fortunately, Black Americans made even greater strides than White Americans with a 27-point increase during that time (23.4% to 50%). 

Similarly, income correlated with expansion in screening rates for 50- to 54-year-olds: Those earning at least 400% over the federal poverty line improved 20 points (from 33.5% to 53.8%), compared with a 16-point improvement in those earning less than 200% above the poverty line (from 19.3% to 35%).

Those with private insurance likewise improved 21 points (from 30.7% to 51.7%), while those in this age group without insurance declined, with just 21.2% getting screened in 2018, compared with 28.2% in 2000. Those on public insurance saw a 15-point improvement, from 27.8% in 2000 to 43.1% in 2018.

“The individual and societal burden of colorectal cancer is especially great among younger adults,” the authors wrote.

The reasons for the much lower prevalence of screening in those under 55, the authors suggested, is likely due to less concern about colorectal cancer, less access to medical care (including being underinsured or uninsured), and the barriers created by competing priorities, such as work schedules, family responsibilities, and caregiving. The latter may be particularly true in underserved populations, the authors noted.

“Screening programs must consider the barriers unique to younger adults, ensuring the benefits of screening are equally realized by all population groups,” the authors concluded.

The research was funded by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. One author reported grants from Epigenomics and Freenome and personal fees from Guardant Health. Another author reported personal fees from Freenome, and a third author reported personal fees from Exact Sciences. No other authors had industry disclosures.

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

Adults younger than 55 years were least likely to get screened for colorectal cancer over the past 2 decades, particularly if they were Hispanic or Asian or had a low income, lower education level, or no health insurance, according to a new study published online in Cancer Epidemiology, Biomarkers & Prevention.

The findings have raised concerns that disparities in screening rates will be even greater in adults aged 45-49 years, prompting the need for increased awareness and outreach to ensure that underserved groups have access to screenings.

“Differences in prevalence of screening by race and ethnicity, educational attainment, household income, and health insurance were most pronounced for those ages 50-54 years, whereas older adults experienced larger increases in prevalence across these groups,” wrote Po-Hong Liu, MD, MPH, a clinical investigator at Harvard University, Boston, and his colleagues. “The persistent and worsening disparities we observed in adults 50-54 years may extend to those ages 45-49 as they become eligible for screening.”

The U.S. Preventive Services Task Force shifted their recommendation for colorectal cancer screening in May 2021 to 5 years earlier, advising people to start screenings at 45 instead of 50, which aligns with the recommendations the American Cancer Society made 3 years earlier.

Both organizations made the change because of increasing rates of colorectal cancer in adults under age 50 and research indicating that beginning screenings at age 45 results in fewer cases, fewer deaths, and more life years gained.

“Across all age groups, colorectal cancer screening participation remains below national goals, and the benefits of screening are not equally realized across populations,” senior author Caitlin Murphy, PhD, MPH, associate professor, UTHealth School of Public Health, Houston, said in a prepared statement. “Extra care must be taken to ensure that expanding screening to younger ages does not negatively impact efforts to eliminate disparities in colorectal screening and outcomes nor jeopardize efforts to increase screening initiation among older adults who remain unscreened.”
 

Data analyzed from 8 years over 2 decades

The researchers analyzed data from the CDC’s cross-sectional National Health Interview Survey during 8 years over the past 2 decades: 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018.

The number of participants each year ranged from a low of 21,781 in 2008 to a high of 34,557 in 2013. After excluding participants with a history of colorectal cancer or missing information on screenings, the total population sample included 80,220 participants 50-75 years old.

The researchers considered a person as having been screened if they received at least one recommended screening test within the year covered by the survey, regardless of why they underwent the test.

Recommended tests included sigmoidoscopy, colonoscopy, and stool-based tests for all survey years. In addition, the surveys for 2010, 2015, and 2018 included CT colonography, and the 2018 survey included FIT-DNA.
 

Screening across population groups

Colorectal cancer screening rates have doubled in the past 2 decades, from 36.7% in 2000 to 66.1% in 2018.

Rates are considerably lower, however, for several key groups, including the youngest group. Less than half (47.6%) of those aged 50-54 years received screenings in 2018, though this was still a nearly 20-point improvement over the 28.2% in this age group who were screened in 2000.

Separate from age, several other groups continue to have low screening rates in general, including Hispanics (56.5%, up from 25.9% in 2000), Asians (57.1%, up from 22.6% in 2000), those who have not received a high school degree (53.6%, up from 26.8% in 2000), and those from low income families (56.6%, up from 30.2% in 2000).

The group with the greatest need for more outreach and screenings are people without insurance, only 39.7% of whom were screened in 2018, a modest increase from 30.2% in 2000.

The biggest increase in screenings over time occurred in those aged 70-75 years, from 46.4% in 2000 to 78% in 2018 overall.

Racial/ethnic, economic, education, and insurance-based disparities were particularly evident the younger people were, including in terms of progress made over time.

For example, screenings of non-Hispanic White people aged 50-54 years improved 21 points (30.3% to 51%) between 2000 and 2018, compared with 19 points in Hispanics (16.7% to 35.5%) and 15 points in Asians (17.3% to 32.3%). Fortunately, Black Americans made even greater strides than White Americans with a 27-point increase during that time (23.4% to 50%). 

Similarly, income correlated with expansion in screening rates for 50- to 54-year-olds: Those earning at least 400% over the federal poverty line improved 20 points (from 33.5% to 53.8%), compared with a 16-point improvement in those earning less than 200% above the poverty line (from 19.3% to 35%).

Those with private insurance likewise improved 21 points (from 30.7% to 51.7%), while those in this age group without insurance declined, with just 21.2% getting screened in 2018, compared with 28.2% in 2000. Those on public insurance saw a 15-point improvement, from 27.8% in 2000 to 43.1% in 2018.

“The individual and societal burden of colorectal cancer is especially great among younger adults,” the authors wrote.

The reasons for the much lower prevalence of screening in those under 55, the authors suggested, is likely due to less concern about colorectal cancer, less access to medical care (including being underinsured or uninsured), and the barriers created by competing priorities, such as work schedules, family responsibilities, and caregiving. The latter may be particularly true in underserved populations, the authors noted.

“Screening programs must consider the barriers unique to younger adults, ensuring the benefits of screening are equally realized by all population groups,” the authors concluded.

The research was funded by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. One author reported grants from Epigenomics and Freenome and personal fees from Guardant Health. Another author reported personal fees from Freenome, and a third author reported personal fees from Exact Sciences. No other authors had industry disclosures.

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

Adults younger than 55 years were least likely to get screened for colorectal cancer over the past 2 decades, particularly if they were Hispanic or Asian or had a low income, lower education level, or no health insurance, according to a new study published online in Cancer Epidemiology, Biomarkers & Prevention.

The findings have raised concerns that disparities in screening rates will be even greater in adults aged 45-49 years, prompting the need for increased awareness and outreach to ensure that underserved groups have access to screenings.

“Differences in prevalence of screening by race and ethnicity, educational attainment, household income, and health insurance were most pronounced for those ages 50-54 years, whereas older adults experienced larger increases in prevalence across these groups,” wrote Po-Hong Liu, MD, MPH, a clinical investigator at Harvard University, Boston, and his colleagues. “The persistent and worsening disparities we observed in adults 50-54 years may extend to those ages 45-49 as they become eligible for screening.”

The U.S. Preventive Services Task Force shifted their recommendation for colorectal cancer screening in May 2021 to 5 years earlier, advising people to start screenings at 45 instead of 50, which aligns with the recommendations the American Cancer Society made 3 years earlier.

Both organizations made the change because of increasing rates of colorectal cancer in adults under age 50 and research indicating that beginning screenings at age 45 results in fewer cases, fewer deaths, and more life years gained.

“Across all age groups, colorectal cancer screening participation remains below national goals, and the benefits of screening are not equally realized across populations,” senior author Caitlin Murphy, PhD, MPH, associate professor, UTHealth School of Public Health, Houston, said in a prepared statement. “Extra care must be taken to ensure that expanding screening to younger ages does not negatively impact efforts to eliminate disparities in colorectal screening and outcomes nor jeopardize efforts to increase screening initiation among older adults who remain unscreened.”
 

Data analyzed from 8 years over 2 decades

The researchers analyzed data from the CDC’s cross-sectional National Health Interview Survey during 8 years over the past 2 decades: 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018.

The number of participants each year ranged from a low of 21,781 in 2008 to a high of 34,557 in 2013. After excluding participants with a history of colorectal cancer or missing information on screenings, the total population sample included 80,220 participants 50-75 years old.

The researchers considered a person as having been screened if they received at least one recommended screening test within the year covered by the survey, regardless of why they underwent the test.

Recommended tests included sigmoidoscopy, colonoscopy, and stool-based tests for all survey years. In addition, the surveys for 2010, 2015, and 2018 included CT colonography, and the 2018 survey included FIT-DNA.
 

Screening across population groups

Colorectal cancer screening rates have doubled in the past 2 decades, from 36.7% in 2000 to 66.1% in 2018.

Rates are considerably lower, however, for several key groups, including the youngest group. Less than half (47.6%) of those aged 50-54 years received screenings in 2018, though this was still a nearly 20-point improvement over the 28.2% in this age group who were screened in 2000.

Separate from age, several other groups continue to have low screening rates in general, including Hispanics (56.5%, up from 25.9% in 2000), Asians (57.1%, up from 22.6% in 2000), those who have not received a high school degree (53.6%, up from 26.8% in 2000), and those from low income families (56.6%, up from 30.2% in 2000).

The group with the greatest need for more outreach and screenings are people without insurance, only 39.7% of whom were screened in 2018, a modest increase from 30.2% in 2000.

The biggest increase in screenings over time occurred in those aged 70-75 years, from 46.4% in 2000 to 78% in 2018 overall.

Racial/ethnic, economic, education, and insurance-based disparities were particularly evident the younger people were, including in terms of progress made over time.

For example, screenings of non-Hispanic White people aged 50-54 years improved 21 points (30.3% to 51%) between 2000 and 2018, compared with 19 points in Hispanics (16.7% to 35.5%) and 15 points in Asians (17.3% to 32.3%). Fortunately, Black Americans made even greater strides than White Americans with a 27-point increase during that time (23.4% to 50%). 

Similarly, income correlated with expansion in screening rates for 50- to 54-year-olds: Those earning at least 400% over the federal poverty line improved 20 points (from 33.5% to 53.8%), compared with a 16-point improvement in those earning less than 200% above the poverty line (from 19.3% to 35%).

Those with private insurance likewise improved 21 points (from 30.7% to 51.7%), while those in this age group without insurance declined, with just 21.2% getting screened in 2018, compared with 28.2% in 2000. Those on public insurance saw a 15-point improvement, from 27.8% in 2000 to 43.1% in 2018.

“The individual and societal burden of colorectal cancer is especially great among younger adults,” the authors wrote.

The reasons for the much lower prevalence of screening in those under 55, the authors suggested, is likely due to less concern about colorectal cancer, less access to medical care (including being underinsured or uninsured), and the barriers created by competing priorities, such as work schedules, family responsibilities, and caregiving. The latter may be particularly true in underserved populations, the authors noted.

“Screening programs must consider the barriers unique to younger adults, ensuring the benefits of screening are equally realized by all population groups,” the authors concluded.

The research was funded by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. One author reported grants from Epigenomics and Freenome and personal fees from Guardant Health. Another author reported personal fees from Freenome, and a third author reported personal fees from Exact Sciences. No other authors had industry disclosures.

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

Kami, a mother of one daughter in central Texas, lost three pregnancies in 2008. The third one nearly killed her.

The embryo became implanted in one of the fallopian tubes connecting her ovaries to her uterus. Because fallopian tubes can’t stretch to accommodate a fetus, patients must undergo surgery to remove the embryo before the tube ruptures. Failure to do so can result in internal bleeding and death.

But when Kami – who did not want to use her last name to avoid harassment – underwent an ultrasound to start the process of extracting the embryo, her doctor miscalculated how far along in the pregnancy she was and told her to come back in a few weeks.

She eventually did return, but only after passing out in the bathtub and waking up in a pool of her own blood. The tube had ruptured, and to remove it, emergency surgery was necessary.

Stories such as Kami’s could become more common in the aftermath of the U.S. Supreme Court’s decision to overturn Roe v. Wade, the 1973 case that created a right to an abortion.

Experts fear that antiabortion laws that take effect in the United States following the court’s decision will lead to a medical and legal limbo for thousands of people like Kami – people with uncommon reproductive conditions whose treatments involve the termination of pregnancies or the destruction of embryos.
 

Vague exceptions prompt concerns

According to the Guttmacher Institute, a nonprofit group for reproductive health, 13 states currently have trigger laws on the books that make abortion illegal in the absence of Roe. Nine other states have laws that would outlaw or severely restrict abortion without a federal right to the procedure.

Each of these laws carves out exceptions that allow the termination of a pregnancy to prevent the death of the pregnant individual. But the language of the provisions is not always precise in describing what those exceptions mean in practice, according to Elizabeth Nash, the principal policy associate for state issues at the Guttmacher Institute.

“These exceptions are designed to be extraordinarily narrow. These aren’t really designed to be usable exceptions,” Ms. Nash said. “There’s so much misinformation about abortion that there are probably legislators out there who think that it’s never needed to save a life.”
 

Tubal pregnancies

One of the best examples of a pregnancy termination that’s necessary to avoid death is in the case of an ectopic pregnancy such as Kami experienced. Without treatment to end the pregnancy, the embryo will eventually grow so large that the tube ruptures, causing massive bleeding that can kill the mother.

Most state laws regarding abortion exclude treatment of ectopic pregnancy, according to Ms. Nash. But, “if the state does not exclude ectopic pregnancy from all the regulations, then people might not be able to get the care that they need when they need it.”

The current abortion law in Texas, for example, prohibits ending a pregnancy after 6 weeks, or after cardiac activity becomes present. Cardiac activity can be present in cases of ectopic pregnancies, which account for between 1% and 2% of all pregnancies and are the leading cause of maternal deaths in the first trimester. And treatment definitely ends the life of the embryo or fetus in the fallopian tube, said Lisa Harris, MD, PhD, an ob.gyn. and medical ethicist at the University of Michigan, Ann Arbor.

Dr. Harris said she has never doubted that an ectopic pregnancy cannot possibly result in a live birth. But she recalled an encounter with another clinician on a surgical team for an ectopic pregnancy who said: “So you’re going to take it out of the tube and put it in the uterus, right?”

“It was a startling moment,” Dr. Harris recalled. She regarded the procedure as a “lifesaving, obvious surgery,” but her colleague, whose suggestion was a medical impossibility since the window of implantation is very brief after fertilization, viewed it “as an abortion, as killing an embryo or fetus.”

Dr. Harris said she isn’t concerned that physicians would stop treating ectopic pregnancies in a post-Roe world. Rather, she worries about two other possibilities: an overzealous prosecutor might not believe it was an ectopic pregnancy and press charges; or laws will cause physicians to second guess their clinical decisions for patients.

“What it means, in the middle of the night, when someone comes in with a 10-week ectopic pregnancy with a heartbeat, is the doctor may hesitate,” Dr. Harris said. Despite knowing the appropriate treatment, the doctor may want to speak with a lawyer or ethicist first to ensure they are covered legally. “And as that process unfolds, which could take hours or days, the person might have a complication.” s

Not treating an ectopic pregnancy would be malpractice, but “some doctors may not provide the standard of care that they would have ordinarily provided because they don’t want to risk breaking the law,” she said.

Even more ambiguous are cornual ectopic pregnancies, in which the implantation occurs at the junction of a fallopian tube and the uterus. These pregnancies, which make up 2%-4% of all tubal pregnancies, are immediately adjacent to the uterus. If an abortion is defined as the termination of an embryo or fetus in the womb, how such a legal definition would apply to these pregnancies is unclear.

An ob.gyn. wouldn’t regard ending an ectopic pregnancy as an abortion, but “this is not about logic or clinical meaning,” Dr. Harris said. “This is people outside of medicine making determinations that all pregnancies must continue, and when you think of a ban that way, you could see why a doctor would be frightened to end a pregnancy, whether it might be viable in the future or not.”

That’s true even if the pregnancy is located fully in the uterus. Dr. Harris described a pregnant patient she saw who had traveled from Texas to Michigan with a fetus that had a lethal defect.

The fetus had “an anomaly where the lungs couldn’t develop, where there were no kidneys. There was no chance this baby could be born and live. Her doctors were very clear that there will never be a baby that [she could] take home at the end of this pregnancy, yet they would not end her pregnancy because that would be an abortion,” Dr. Harris said.

Texas law “doesn’t make any allowances for whether a pregnancy will ever actually result in a baby or not,” Dr. Harris said. “The law, in effect, just says all pregnancies must continue.”
 

Selective reduction

How abortion laws in different states might affect selective reduction, which is used in some pregnancies to reduce the total number of fetuses a person is carrying, is even more ambiguous. The goal of selective reduction is to decrease health risks to the pregnant individual and increase the likelihood of survival for the remaining fetuses. Current Texas law prohibits these procedures.

Someone pregnant with quintuplets, for example, might seek selection reduction to reduce the pregnancy outcome to triplets or twins. A related procedure, selective termination, is used to terminate the life of a fetus with abnormalities while the pregnancy of the fetus’ in utero siblings continues.

The advent of assisted reproduction methods, such as in vitro fertilization (IVF), greatly increased the incidence of higher-order multiples, those with three or more fetuses. The first IVF baby was born in 1978. By 1998, the rate of higher-order multiple births was 1.9 per 1,000 births, five times the figure in 1980. The rate has since decreased by nearly half, to 1 per 1,000 births, but with 3.75 million live births a year, that’s still a lot of pregnancies with higher-order multiples.

The American College of Obstetricians and Gynecologists does not provide explicit guidance on when selective reduction is warranted, but its committee opinion on multifetal pregnancy reduction provides an ethical framework for providers to use when counseling people with pregnancies of three or more fetuses. How would various state laws that outlaw abortion affect these decisions? No one knows.

“Selective reduction ends the life of a fetus or embryo, but it doesn’t end the pregnancy,” Dr. Harris said. “So, if the pregnancy continues but it kills an embryo or fetus, is that an abortion?”
 

‘The question of the hour’

Dr. Harris and other doctors are haunted by potential medical cases in which continuing a pregnancy may result in the death of the person carrying the fetus but in which such death may not be so imminent that the law would allow immediate termination of the pregnancy.

Michael Northrup, MD, an intensive care pediatrician in Winston-Salem, N.C., recalled a particularly harrowing case that illustrates the peril in deciding when someone’s life is “enough” in danger to qualify as an exception to abortion bans.

The 14-year-old girl had severe lupus and kidney failure that required treatment with methotrexate and immediate dialysis to replace her electrolytes. A standard pretreatment pregnancy test revealed that she had been carrying a child for at least 10 weeks. Her pregnancy presented two problems. Methotrexate is so severely toxic that it’s sometimes used to end pregnancies. Even at low doses, fetuses that survive usually have severe deformities. In addition, dialysis requires administration of a blood thinner. If the teen miscarried while taking a blood thinner during dialysis, she risked bleeding to death.

Treatment could be delayed until week 24 of pregnancy, at which time delivery could be attempted, but the patient likely wouldn’t have any kidney function left by then. In addition, at 24 weeks, it was unlikely that the baby would survive anyway.

Dr. Northrup said that, had she chosen that route, “I’m not sure she would have made it. This was a religious family, people who very much were believers. They had their head of church come in, who fairly quickly determined that the best thing for her health was to terminate this pregnancy immediately and get the treatment she needed for her body.”

Would such a situation qualify for an emergency termination? The girl wasn’t going to die within 24 or 48 hours, but it may not have been possible to pinpoint the time of death within a day or 2.

“The family was sad, but they made that choice, and I wonder, would we have to justify that with these new laws?” Dr. Northrup said. “You definitely worry, being in the hot seat, ‘Does this count enough? Is she close enough to death?’ ”

The same question comes up when someone’s water breaks early in the second trimester. Since a live-birth delivery would be highly unlikely, given the age of the fetus, the standard of care is to offer to terminate the pregnancy to avoid a serious infection, Dr. Harris said. But if the infection hasn’t yet developed – even if it’s likely to develop soon – doctors in a state that outlaws abortion would not be able to offer termination. But as providers wait for an infection to develop, the person’s risk of dying from infection rapidly increases.

“How likely does someone need to be to die for it to count to get a life-preserving abortion?” Dr. Harris asked. “That, I think, is the question of the hour.”

Different institutions may decide to determine their own risk thresholds. One hospital, for example, may decide that any health threat that is associated with a 10% risk of death qualifies for a lifesaving abortion. But for many people, a 1 in 10 chance of dying is quite high.

“Who gets to decide what’s meaningful?” Dr. Harris asked, especially if the patient is already a parent of living children and doesn’t want to take any risk at all of orphaning them for a pregnancy with severe complications.

“The point is that this is way more complicated than anybody really knows, way more complicated than any legislator or justice could possibly know, and it creates all kinds of complicated ambiguities, some of which could result in harm to women,” she said. “I’ve been a doctor almost 30 years, and every week, sometimes every day, I’m humbled by how complicated pregnancy is and how complicated people’s bodies and life situations are.”

That’s what makes it so dangerous for policymakers to “insert themselves into medical practice,” Ms. Nash said. She worries about the legal ramifications of overturning Roe, such as prosecution of people who illegally undergo an abortion or of physicians who perform a procedure that a judge deems to be in violation of abortion law.

“There are already local prosecutors who have misused the law to go after people who have managed their own abortions,” Ms. Nash said. “Criminal abortion law, fetal homicide, child neglect, practicing medicine without a license – these are things people have actually been arrested and convicted under.”

Some laws may target the person seeking an abortion, whereas others may target clinicians providing abortions, or even people who simply help someone obtain an abortion, as the Texas law does. In Dr. Harris’s own state of Michigan, a group of Republican lawmakers recently introduced a bill that would imprison abortion providers for up to 10 years and anyone creating or distributing abortion medication for up to 20 years.

Michigan Gov. Gretchen Whitmer, a Democrat who called the proposed legislation “disturbing” and “infuriating,” would almost certainly veto the bill, but it’s just one of dozens already filed or that are expected to be filed across the United States.

The antiabortion organization National Right to Life has published a “post-Roe model abortion law” for states to adopt. The model includes an exemption for abortions that, “based on reasonable medical judgment, [were] necessary to prevent the death of the pregnant woman” – but, again, it does not clarify what that means in practice.
 

Lectures from strangers

Four years after nearly dying, Kami gave birth to a healthy girl following an uncomplicated pregnancy. But her journey to having more children presented more challenges.

Two years after the birth of her child, she had another ectopic pregnancy. Her doctor sent her prescriptions for medication that would end this pregnancy, but a pharmacist refused to fill the prescription.

“Do you know these are very serious medications?” the pharmacist asked her. She did – she had taken them once before for another ectopic pregnancy. She was with her daughter, feeling devastated about losing yet another desired pregnancy. She simply wanted to get the medication and go home.

“‘So you’re trying to have a cheap abortion,’ he said, and 30 heads turned and looked at me. The whole pharmacy heard,” Kami said.

She told the pharmacist that she’d miscarried. She said he responded with: “So you have a dead baby in your body.”

Even after her doctor called to insist on filling the order, the man refused to fill it.

Kami left without the prescription, and her doctor performed a surgical dilation and curettage to remove the embryo from her fallopian tube for no fee.

Kami later tried again to have more children. She experienced another ruptured tube that she said nearly killed her.

“There was such a sense of pain knowing that I couldn’t have any more kids, but also the relief of knowing that I don’t have to go through this again,” Kami said. Now, however, with the Supreme Court having overturned Roe v. Wade, she has a new worry: “That my daughter will not have the same rights and access to health care that I did.”

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

Kami, a mother of one daughter in central Texas, lost three pregnancies in 2008. The third one nearly killed her.

The embryo became implanted in one of the fallopian tubes connecting her ovaries to her uterus. Because fallopian tubes can’t stretch to accommodate a fetus, patients must undergo surgery to remove the embryo before the tube ruptures. Failure to do so can result in internal bleeding and death.

But when Kami – who did not want to use her last name to avoid harassment – underwent an ultrasound to start the process of extracting the embryo, her doctor miscalculated how far along in the pregnancy she was and told her to come back in a few weeks.

She eventually did return, but only after passing out in the bathtub and waking up in a pool of her own blood. The tube had ruptured, and to remove it, emergency surgery was necessary.

Stories such as Kami’s could become more common in the aftermath of the U.S. Supreme Court’s decision to overturn Roe v. Wade, the 1973 case that created a right to an abortion.

Experts fear that antiabortion laws that take effect in the United States following the court’s decision will lead to a medical and legal limbo for thousands of people like Kami – people with uncommon reproductive conditions whose treatments involve the termination of pregnancies or the destruction of embryos.
 

Vague exceptions prompt concerns

According to the Guttmacher Institute, a nonprofit group for reproductive health, 13 states currently have trigger laws on the books that make abortion illegal in the absence of Roe. Nine other states have laws that would outlaw or severely restrict abortion without a federal right to the procedure.

Each of these laws carves out exceptions that allow the termination of a pregnancy to prevent the death of the pregnant individual. But the language of the provisions is not always precise in describing what those exceptions mean in practice, according to Elizabeth Nash, the principal policy associate for state issues at the Guttmacher Institute.

“These exceptions are designed to be extraordinarily narrow. These aren’t really designed to be usable exceptions,” Ms. Nash said. “There’s so much misinformation about abortion that there are probably legislators out there who think that it’s never needed to save a life.”
 

Tubal pregnancies

One of the best examples of a pregnancy termination that’s necessary to avoid death is in the case of an ectopic pregnancy such as Kami experienced. Without treatment to end the pregnancy, the embryo will eventually grow so large that the tube ruptures, causing massive bleeding that can kill the mother.

Most state laws regarding abortion exclude treatment of ectopic pregnancy, according to Ms. Nash. But, “if the state does not exclude ectopic pregnancy from all the regulations, then people might not be able to get the care that they need when they need it.”

The current abortion law in Texas, for example, prohibits ending a pregnancy after 6 weeks, or after cardiac activity becomes present. Cardiac activity can be present in cases of ectopic pregnancies, which account for between 1% and 2% of all pregnancies and are the leading cause of maternal deaths in the first trimester. And treatment definitely ends the life of the embryo or fetus in the fallopian tube, said Lisa Harris, MD, PhD, an ob.gyn. and medical ethicist at the University of Michigan, Ann Arbor.

Dr. Harris said she has never doubted that an ectopic pregnancy cannot possibly result in a live birth. But she recalled an encounter with another clinician on a surgical team for an ectopic pregnancy who said: “So you’re going to take it out of the tube and put it in the uterus, right?”

“It was a startling moment,” Dr. Harris recalled. She regarded the procedure as a “lifesaving, obvious surgery,” but her colleague, whose suggestion was a medical impossibility since the window of implantation is very brief after fertilization, viewed it “as an abortion, as killing an embryo or fetus.”

Dr. Harris said she isn’t concerned that physicians would stop treating ectopic pregnancies in a post-Roe world. Rather, she worries about two other possibilities: an overzealous prosecutor might not believe it was an ectopic pregnancy and press charges; or laws will cause physicians to second guess their clinical decisions for patients.

“What it means, in the middle of the night, when someone comes in with a 10-week ectopic pregnancy with a heartbeat, is the doctor may hesitate,” Dr. Harris said. Despite knowing the appropriate treatment, the doctor may want to speak with a lawyer or ethicist first to ensure they are covered legally. “And as that process unfolds, which could take hours or days, the person might have a complication.” s

Not treating an ectopic pregnancy would be malpractice, but “some doctors may not provide the standard of care that they would have ordinarily provided because they don’t want to risk breaking the law,” she said.

Even more ambiguous are cornual ectopic pregnancies, in which the implantation occurs at the junction of a fallopian tube and the uterus. These pregnancies, which make up 2%-4% of all tubal pregnancies, are immediately adjacent to the uterus. If an abortion is defined as the termination of an embryo or fetus in the womb, how such a legal definition would apply to these pregnancies is unclear.

An ob.gyn. wouldn’t regard ending an ectopic pregnancy as an abortion, but “this is not about logic or clinical meaning,” Dr. Harris said. “This is people outside of medicine making determinations that all pregnancies must continue, and when you think of a ban that way, you could see why a doctor would be frightened to end a pregnancy, whether it might be viable in the future or not.”

That’s true even if the pregnancy is located fully in the uterus. Dr. Harris described a pregnant patient she saw who had traveled from Texas to Michigan with a fetus that had a lethal defect.

The fetus had “an anomaly where the lungs couldn’t develop, where there were no kidneys. There was no chance this baby could be born and live. Her doctors were very clear that there will never be a baby that [she could] take home at the end of this pregnancy, yet they would not end her pregnancy because that would be an abortion,” Dr. Harris said.

Texas law “doesn’t make any allowances for whether a pregnancy will ever actually result in a baby or not,” Dr. Harris said. “The law, in effect, just says all pregnancies must continue.”
 

Selective reduction

How abortion laws in different states might affect selective reduction, which is used in some pregnancies to reduce the total number of fetuses a person is carrying, is even more ambiguous. The goal of selective reduction is to decrease health risks to the pregnant individual and increase the likelihood of survival for the remaining fetuses. Current Texas law prohibits these procedures.

Someone pregnant with quintuplets, for example, might seek selection reduction to reduce the pregnancy outcome to triplets or twins. A related procedure, selective termination, is used to terminate the life of a fetus with abnormalities while the pregnancy of the fetus’ in utero siblings continues.

The advent of assisted reproduction methods, such as in vitro fertilization (IVF), greatly increased the incidence of higher-order multiples, those with three or more fetuses. The first IVF baby was born in 1978. By 1998, the rate of higher-order multiple births was 1.9 per 1,000 births, five times the figure in 1980. The rate has since decreased by nearly half, to 1 per 1,000 births, but with 3.75 million live births a year, that’s still a lot of pregnancies with higher-order multiples.

The American College of Obstetricians and Gynecologists does not provide explicit guidance on when selective reduction is warranted, but its committee opinion on multifetal pregnancy reduction provides an ethical framework for providers to use when counseling people with pregnancies of three or more fetuses. How would various state laws that outlaw abortion affect these decisions? No one knows.

“Selective reduction ends the life of a fetus or embryo, but it doesn’t end the pregnancy,” Dr. Harris said. “So, if the pregnancy continues but it kills an embryo or fetus, is that an abortion?”
 

‘The question of the hour’

Dr. Harris and other doctors are haunted by potential medical cases in which continuing a pregnancy may result in the death of the person carrying the fetus but in which such death may not be so imminent that the law would allow immediate termination of the pregnancy.

Michael Northrup, MD, an intensive care pediatrician in Winston-Salem, N.C., recalled a particularly harrowing case that illustrates the peril in deciding when someone’s life is “enough” in danger to qualify as an exception to abortion bans.

The 14-year-old girl had severe lupus and kidney failure that required treatment with methotrexate and immediate dialysis to replace her electrolytes. A standard pretreatment pregnancy test revealed that she had been carrying a child for at least 10 weeks. Her pregnancy presented two problems. Methotrexate is so severely toxic that it’s sometimes used to end pregnancies. Even at low doses, fetuses that survive usually have severe deformities. In addition, dialysis requires administration of a blood thinner. If the teen miscarried while taking a blood thinner during dialysis, she risked bleeding to death.

Treatment could be delayed until week 24 of pregnancy, at which time delivery could be attempted, but the patient likely wouldn’t have any kidney function left by then. In addition, at 24 weeks, it was unlikely that the baby would survive anyway.

Dr. Northrup said that, had she chosen that route, “I’m not sure she would have made it. This was a religious family, people who very much were believers. They had their head of church come in, who fairly quickly determined that the best thing for her health was to terminate this pregnancy immediately and get the treatment she needed for her body.”

Would such a situation qualify for an emergency termination? The girl wasn’t going to die within 24 or 48 hours, but it may not have been possible to pinpoint the time of death within a day or 2.

“The family was sad, but they made that choice, and I wonder, would we have to justify that with these new laws?” Dr. Northrup said. “You definitely worry, being in the hot seat, ‘Does this count enough? Is she close enough to death?’ ”

The same question comes up when someone’s water breaks early in the second trimester. Since a live-birth delivery would be highly unlikely, given the age of the fetus, the standard of care is to offer to terminate the pregnancy to avoid a serious infection, Dr. Harris said. But if the infection hasn’t yet developed – even if it’s likely to develop soon – doctors in a state that outlaws abortion would not be able to offer termination. But as providers wait for an infection to develop, the person’s risk of dying from infection rapidly increases.

“How likely does someone need to be to die for it to count to get a life-preserving abortion?” Dr. Harris asked. “That, I think, is the question of the hour.”

Different institutions may decide to determine their own risk thresholds. One hospital, for example, may decide that any health threat that is associated with a 10% risk of death qualifies for a lifesaving abortion. But for many people, a 1 in 10 chance of dying is quite high.

“Who gets to decide what’s meaningful?” Dr. Harris asked, especially if the patient is already a parent of living children and doesn’t want to take any risk at all of orphaning them for a pregnancy with severe complications.

“The point is that this is way more complicated than anybody really knows, way more complicated than any legislator or justice could possibly know, and it creates all kinds of complicated ambiguities, some of which could result in harm to women,” she said. “I’ve been a doctor almost 30 years, and every week, sometimes every day, I’m humbled by how complicated pregnancy is and how complicated people’s bodies and life situations are.”

That’s what makes it so dangerous for policymakers to “insert themselves into medical practice,” Ms. Nash said. She worries about the legal ramifications of overturning Roe, such as prosecution of people who illegally undergo an abortion or of physicians who perform a procedure that a judge deems to be in violation of abortion law.

“There are already local prosecutors who have misused the law to go after people who have managed their own abortions,” Ms. Nash said. “Criminal abortion law, fetal homicide, child neglect, practicing medicine without a license – these are things people have actually been arrested and convicted under.”

Some laws may target the person seeking an abortion, whereas others may target clinicians providing abortions, or even people who simply help someone obtain an abortion, as the Texas law does. In Dr. Harris’s own state of Michigan, a group of Republican lawmakers recently introduced a bill that would imprison abortion providers for up to 10 years and anyone creating or distributing abortion medication for up to 20 years.

Michigan Gov. Gretchen Whitmer, a Democrat who called the proposed legislation “disturbing” and “infuriating,” would almost certainly veto the bill, but it’s just one of dozens already filed or that are expected to be filed across the United States.

The antiabortion organization National Right to Life has published a “post-Roe model abortion law” for states to adopt. The model includes an exemption for abortions that, “based on reasonable medical judgment, [were] necessary to prevent the death of the pregnant woman” – but, again, it does not clarify what that means in practice.
 

Lectures from strangers

Four years after nearly dying, Kami gave birth to a healthy girl following an uncomplicated pregnancy. But her journey to having more children presented more challenges.

Two years after the birth of her child, she had another ectopic pregnancy. Her doctor sent her prescriptions for medication that would end this pregnancy, but a pharmacist refused to fill the prescription.

“Do you know these are very serious medications?” the pharmacist asked her. She did – she had taken them once before for another ectopic pregnancy. She was with her daughter, feeling devastated about losing yet another desired pregnancy. She simply wanted to get the medication and go home.

“‘So you’re trying to have a cheap abortion,’ he said, and 30 heads turned and looked at me. The whole pharmacy heard,” Kami said.

She told the pharmacist that she’d miscarried. She said he responded with: “So you have a dead baby in your body.”

Even after her doctor called to insist on filling the order, the man refused to fill it.

Kami left without the prescription, and her doctor performed a surgical dilation and curettage to remove the embryo from her fallopian tube for no fee.

Kami later tried again to have more children. She experienced another ruptured tube that she said nearly killed her.

“There was such a sense of pain knowing that I couldn’t have any more kids, but also the relief of knowing that I don’t have to go through this again,” Kami said. Now, however, with the Supreme Court having overturned Roe v. Wade, she has a new worry: “That my daughter will not have the same rights and access to health care that I did.”

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

Kami, a mother of one daughter in central Texas, lost three pregnancies in 2008. The third one nearly killed her.

The embryo became implanted in one of the fallopian tubes connecting her ovaries to her uterus. Because fallopian tubes can’t stretch to accommodate a fetus, patients must undergo surgery to remove the embryo before the tube ruptures. Failure to do so can result in internal bleeding and death.

But when Kami – who did not want to use her last name to avoid harassment – underwent an ultrasound to start the process of extracting the embryo, her doctor miscalculated how far along in the pregnancy she was and told her to come back in a few weeks.

She eventually did return, but only after passing out in the bathtub and waking up in a pool of her own blood. The tube had ruptured, and to remove it, emergency surgery was necessary.

Stories such as Kami’s could become more common in the aftermath of the U.S. Supreme Court’s decision to overturn Roe v. Wade, the 1973 case that created a right to an abortion.

Experts fear that antiabortion laws that take effect in the United States following the court’s decision will lead to a medical and legal limbo for thousands of people like Kami – people with uncommon reproductive conditions whose treatments involve the termination of pregnancies or the destruction of embryos.
 

Vague exceptions prompt concerns

According to the Guttmacher Institute, a nonprofit group for reproductive health, 13 states currently have trigger laws on the books that make abortion illegal in the absence of Roe. Nine other states have laws that would outlaw or severely restrict abortion without a federal right to the procedure.

Each of these laws carves out exceptions that allow the termination of a pregnancy to prevent the death of the pregnant individual. But the language of the provisions is not always precise in describing what those exceptions mean in practice, according to Elizabeth Nash, the principal policy associate for state issues at the Guttmacher Institute.

“These exceptions are designed to be extraordinarily narrow. These aren’t really designed to be usable exceptions,” Ms. Nash said. “There’s so much misinformation about abortion that there are probably legislators out there who think that it’s never needed to save a life.”
 

Tubal pregnancies

One of the best examples of a pregnancy termination that’s necessary to avoid death is in the case of an ectopic pregnancy such as Kami experienced. Without treatment to end the pregnancy, the embryo will eventually grow so large that the tube ruptures, causing massive bleeding that can kill the mother.

Most state laws regarding abortion exclude treatment of ectopic pregnancy, according to Ms. Nash. But, “if the state does not exclude ectopic pregnancy from all the regulations, then people might not be able to get the care that they need when they need it.”

The current abortion law in Texas, for example, prohibits ending a pregnancy after 6 weeks, or after cardiac activity becomes present. Cardiac activity can be present in cases of ectopic pregnancies, which account for between 1% and 2% of all pregnancies and are the leading cause of maternal deaths in the first trimester. And treatment definitely ends the life of the embryo or fetus in the fallopian tube, said Lisa Harris, MD, PhD, an ob.gyn. and medical ethicist at the University of Michigan, Ann Arbor.

Dr. Harris said she has never doubted that an ectopic pregnancy cannot possibly result in a live birth. But she recalled an encounter with another clinician on a surgical team for an ectopic pregnancy who said: “So you’re going to take it out of the tube and put it in the uterus, right?”

“It was a startling moment,” Dr. Harris recalled. She regarded the procedure as a “lifesaving, obvious surgery,” but her colleague, whose suggestion was a medical impossibility since the window of implantation is very brief after fertilization, viewed it “as an abortion, as killing an embryo or fetus.”

Dr. Harris said she isn’t concerned that physicians would stop treating ectopic pregnancies in a post-Roe world. Rather, she worries about two other possibilities: an overzealous prosecutor might not believe it was an ectopic pregnancy and press charges; or laws will cause physicians to second guess their clinical decisions for patients.

“What it means, in the middle of the night, when someone comes in with a 10-week ectopic pregnancy with a heartbeat, is the doctor may hesitate,” Dr. Harris said. Despite knowing the appropriate treatment, the doctor may want to speak with a lawyer or ethicist first to ensure they are covered legally. “And as that process unfolds, which could take hours or days, the person might have a complication.” s

Not treating an ectopic pregnancy would be malpractice, but “some doctors may not provide the standard of care that they would have ordinarily provided because they don’t want to risk breaking the law,” she said.

Even more ambiguous are cornual ectopic pregnancies, in which the implantation occurs at the junction of a fallopian tube and the uterus. These pregnancies, which make up 2%-4% of all tubal pregnancies, are immediately adjacent to the uterus. If an abortion is defined as the termination of an embryo or fetus in the womb, how such a legal definition would apply to these pregnancies is unclear.

An ob.gyn. wouldn’t regard ending an ectopic pregnancy as an abortion, but “this is not about logic or clinical meaning,” Dr. Harris said. “This is people outside of medicine making determinations that all pregnancies must continue, and when you think of a ban that way, you could see why a doctor would be frightened to end a pregnancy, whether it might be viable in the future or not.”

That’s true even if the pregnancy is located fully in the uterus. Dr. Harris described a pregnant patient she saw who had traveled from Texas to Michigan with a fetus that had a lethal defect.

The fetus had “an anomaly where the lungs couldn’t develop, where there were no kidneys. There was no chance this baby could be born and live. Her doctors were very clear that there will never be a baby that [she could] take home at the end of this pregnancy, yet they would not end her pregnancy because that would be an abortion,” Dr. Harris said.

Texas law “doesn’t make any allowances for whether a pregnancy will ever actually result in a baby or not,” Dr. Harris said. “The law, in effect, just says all pregnancies must continue.”
 

Selective reduction

How abortion laws in different states might affect selective reduction, which is used in some pregnancies to reduce the total number of fetuses a person is carrying, is even more ambiguous. The goal of selective reduction is to decrease health risks to the pregnant individual and increase the likelihood of survival for the remaining fetuses. Current Texas law prohibits these procedures.

Someone pregnant with quintuplets, for example, might seek selection reduction to reduce the pregnancy outcome to triplets or twins. A related procedure, selective termination, is used to terminate the life of a fetus with abnormalities while the pregnancy of the fetus’ in utero siblings continues.

The advent of assisted reproduction methods, such as in vitro fertilization (IVF), greatly increased the incidence of higher-order multiples, those with three or more fetuses. The first IVF baby was born in 1978. By 1998, the rate of higher-order multiple births was 1.9 per 1,000 births, five times the figure in 1980. The rate has since decreased by nearly half, to 1 per 1,000 births, but with 3.75 million live births a year, that’s still a lot of pregnancies with higher-order multiples.

The American College of Obstetricians and Gynecologists does not provide explicit guidance on when selective reduction is warranted, but its committee opinion on multifetal pregnancy reduction provides an ethical framework for providers to use when counseling people with pregnancies of three or more fetuses. How would various state laws that outlaw abortion affect these decisions? No one knows.

“Selective reduction ends the life of a fetus or embryo, but it doesn’t end the pregnancy,” Dr. Harris said. “So, if the pregnancy continues but it kills an embryo or fetus, is that an abortion?”
 

‘The question of the hour’

Dr. Harris and other doctors are haunted by potential medical cases in which continuing a pregnancy may result in the death of the person carrying the fetus but in which such death may not be so imminent that the law would allow immediate termination of the pregnancy.

Michael Northrup, MD, an intensive care pediatrician in Winston-Salem, N.C., recalled a particularly harrowing case that illustrates the peril in deciding when someone’s life is “enough” in danger to qualify as an exception to abortion bans.

The 14-year-old girl had severe lupus and kidney failure that required treatment with methotrexate and immediate dialysis to replace her electrolytes. A standard pretreatment pregnancy test revealed that she had been carrying a child for at least 10 weeks. Her pregnancy presented two problems. Methotrexate is so severely toxic that it’s sometimes used to end pregnancies. Even at low doses, fetuses that survive usually have severe deformities. In addition, dialysis requires administration of a blood thinner. If the teen miscarried while taking a blood thinner during dialysis, she risked bleeding to death.

Treatment could be delayed until week 24 of pregnancy, at which time delivery could be attempted, but the patient likely wouldn’t have any kidney function left by then. In addition, at 24 weeks, it was unlikely that the baby would survive anyway.

Dr. Northrup said that, had she chosen that route, “I’m not sure she would have made it. This was a religious family, people who very much were believers. They had their head of church come in, who fairly quickly determined that the best thing for her health was to terminate this pregnancy immediately and get the treatment she needed for her body.”

Would such a situation qualify for an emergency termination? The girl wasn’t going to die within 24 or 48 hours, but it may not have been possible to pinpoint the time of death within a day or 2.

“The family was sad, but they made that choice, and I wonder, would we have to justify that with these new laws?” Dr. Northrup said. “You definitely worry, being in the hot seat, ‘Does this count enough? Is she close enough to death?’ ”

The same question comes up when someone’s water breaks early in the second trimester. Since a live-birth delivery would be highly unlikely, given the age of the fetus, the standard of care is to offer to terminate the pregnancy to avoid a serious infection, Dr. Harris said. But if the infection hasn’t yet developed – even if it’s likely to develop soon – doctors in a state that outlaws abortion would not be able to offer termination. But as providers wait for an infection to develop, the person’s risk of dying from infection rapidly increases.

“How likely does someone need to be to die for it to count to get a life-preserving abortion?” Dr. Harris asked. “That, I think, is the question of the hour.”

Different institutions may decide to determine their own risk thresholds. One hospital, for example, may decide that any health threat that is associated with a 10% risk of death qualifies for a lifesaving abortion. But for many people, a 1 in 10 chance of dying is quite high.

“Who gets to decide what’s meaningful?” Dr. Harris asked, especially if the patient is already a parent of living children and doesn’t want to take any risk at all of orphaning them for a pregnancy with severe complications.

“The point is that this is way more complicated than anybody really knows, way more complicated than any legislator or justice could possibly know, and it creates all kinds of complicated ambiguities, some of which could result in harm to women,” she said. “I’ve been a doctor almost 30 years, and every week, sometimes every day, I’m humbled by how complicated pregnancy is and how complicated people’s bodies and life situations are.”

That’s what makes it so dangerous for policymakers to “insert themselves into medical practice,” Ms. Nash said. She worries about the legal ramifications of overturning Roe, such as prosecution of people who illegally undergo an abortion or of physicians who perform a procedure that a judge deems to be in violation of abortion law.

“There are already local prosecutors who have misused the law to go after people who have managed their own abortions,” Ms. Nash said. “Criminal abortion law, fetal homicide, child neglect, practicing medicine without a license – these are things people have actually been arrested and convicted under.”

Some laws may target the person seeking an abortion, whereas others may target clinicians providing abortions, or even people who simply help someone obtain an abortion, as the Texas law does. In Dr. Harris’s own state of Michigan, a group of Republican lawmakers recently introduced a bill that would imprison abortion providers for up to 10 years and anyone creating or distributing abortion medication for up to 20 years.

Michigan Gov. Gretchen Whitmer, a Democrat who called the proposed legislation “disturbing” and “infuriating,” would almost certainly veto the bill, but it’s just one of dozens already filed or that are expected to be filed across the United States.

The antiabortion organization National Right to Life has published a “post-Roe model abortion law” for states to adopt. The model includes an exemption for abortions that, “based on reasonable medical judgment, [were] necessary to prevent the death of the pregnant woman” – but, again, it does not clarify what that means in practice.
 

Lectures from strangers

Four years after nearly dying, Kami gave birth to a healthy girl following an uncomplicated pregnancy. But her journey to having more children presented more challenges.

Two years after the birth of her child, she had another ectopic pregnancy. Her doctor sent her prescriptions for medication that would end this pregnancy, but a pharmacist refused to fill the prescription.

“Do you know these are very serious medications?” the pharmacist asked her. She did – she had taken them once before for another ectopic pregnancy. She was with her daughter, feeling devastated about losing yet another desired pregnancy. She simply wanted to get the medication and go home.

“‘So you’re trying to have a cheap abortion,’ he said, and 30 heads turned and looked at me. The whole pharmacy heard,” Kami said.

She told the pharmacist that she’d miscarried. She said he responded with: “So you have a dead baby in your body.”

Even after her doctor called to insist on filling the order, the man refused to fill it.

Kami left without the prescription, and her doctor performed a surgical dilation and curettage to remove the embryo from her fallopian tube for no fee.

Kami later tried again to have more children. She experienced another ruptured tube that she said nearly killed her.

“There was such a sense of pain knowing that I couldn’t have any more kids, but also the relief of knowing that I don’t have to go through this again,” Kami said. Now, however, with the Supreme Court having overturned Roe v. Wade, she has a new worry: “That my daughter will not have the same rights and access to health care that I did.”

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

Ongoing research in patients with oligoarticular juvenile idiopathic arthritis (JIA) so far suggests that a set of biomarkers in synovial fluid may help to predict which patients may be more likely to stay with persistent oligoarticular disease rather than progress to polyarticular disease, according to new research presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance, held virtually this year. Identifying biomarkers in synovial fluid or possibly serum could aid families and physicians in being more proactive in treatment protocols, said AnneMarie C. Brescia, MD, of Nemours Children’s Hospital in Wilmington, Del.

“JIA carries the risk of permanent joint damage and disability, which can result when joint involvement evolves from oligoarticular into a polyarticular course, termed extended oligoarticular disease,” Dr. Brescia told attendees. “Since disease progression increases the risk for disability, early prediction of this course is essential.”

This group – those whose oligoarticular disease will begin recruiting joints and ultimately become extended oligoarticular JIA – is “very important because they have been shown to have worse health-related quality of life and greater risk of needing a joint replacement than even polyarticular [JIA],” Dr. Brescia said. “So, our lab has really focused on trying to predict who will fall in this group.”

Melissa Oliver, MD, assistant professor of clinical pediatrics in the division of pediatric rheumatology at Indiana University in Indianapolis, was not involved in the study but agreed that having highly sensitive and specific biomarkers could be particularly helpful in clinical care.

“Biomarkers can help guide treatment decisions and help physicians and their patients share the decision-making about next choices and when to change,” Dr. Oliver told this news organization. “If a provider and parent know that their child has these markers in their serum or synovial fluid that may predict extension of their disease, then they may be more aggressive upfront with therapy.”

The study aimed to determine whether differential levels of synovial fluid proteins could be used to predict whether JIA would evolve into an extended course before it became clinically evident. Although early aggressive treatment is common with rheumatoid arthritis and can lead to remission, JIA treatment paradigms tend to be more reactive, Dr. Brescia said.

“It would be better to switch to proactive, that if we’re able to predict that this patient may have a more difficult course with extension to polyarticular, we could be prepared, we could inform the parents, and it would just help us have a more proactive approach,” she said.

The researchers used antibody arrays to detect the following inflammatory mediators in blinded samples: CD14, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, vascular endothelial growth factor (VEGF), and angiogenin. They analyzed 37 samples with persistent disease and 32 samples from disease that had not yet extended but would become extended in that patient. The samples came from patients who were taking no medicines or only NSAIDs. The researchers assessed the sensitivity and specificity of each biomarker. Sensitivity referred the biomarker’s ability to correctly indicate that the sample would extend, and specificity referred to the biomarker’s accuracy in determining that the disease in the sample would remain persistent.

Combining samples from cohorts at Nemours Children’s Health (14 persistent and 7 extended-to-be) and Cincinnati Children’s Hospital (23 persistent and 25 extended-to-be) yielded the following results:

“This is a work in progress,” Dr. Brescia said, “so hopefully you’ll hear about it next year.” In response to an attendee’s question, she said she believes identifying reliable biomarkers will eventually lead to refining treatment paradigms.

“I think it will at least change the guidance we can provide parents about making next choices and how quickly to accelerate to those next choices,” Dr. Brescia said. For example, if a child’s serum or synovial fluid has markers that show a very high likelihood of extension, the parent may decide to proceed to the next level medication sooner. “I do think it will push both parents and doctors to be a little more proactive instead of reactive when the poor patient comes back with 13 joints involved when they had just been an oligo for years.”

Dr. Oliver noted the promise of CD14 and IL-6 in potentially predicting which patients’ disease will stay persistent but cautioned that it’s still early in evaluating these biomarkers, especially with the limited patient samples in this study.

“I think these results are promising, and it’s great that there are groups out there working on this,” Dr. Oliver said. “Once we have a reliable, highly sensitive and specific biomarker, that will definitely help providers, parents, and patients be more informed.”

The research was supported by the Open Net Foundation, the Arthritis Foundation, Delaware Community Foundation, the Delaware Clinical and Translational Research (DE-CTR) ACCEL Program, the Nancy Taylor Foundation for Chronic Diseases, and CARRA. Dr. Brescia and Dr. Oliver have disclosed no relevant financial relationships.

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

Ongoing research in patients with oligoarticular juvenile idiopathic arthritis (JIA) so far suggests that a set of biomarkers in synovial fluid may help to predict which patients may be more likely to stay with persistent oligoarticular disease rather than progress to polyarticular disease, according to new research presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance, held virtually this year. Identifying biomarkers in synovial fluid or possibly serum could aid families and physicians in being more proactive in treatment protocols, said AnneMarie C. Brescia, MD, of Nemours Children’s Hospital in Wilmington, Del.

“JIA carries the risk of permanent joint damage and disability, which can result when joint involvement evolves from oligoarticular into a polyarticular course, termed extended oligoarticular disease,” Dr. Brescia told attendees. “Since disease progression increases the risk for disability, early prediction of this course is essential.”

This group – those whose oligoarticular disease will begin recruiting joints and ultimately become extended oligoarticular JIA – is “very important because they have been shown to have worse health-related quality of life and greater risk of needing a joint replacement than even polyarticular [JIA],” Dr. Brescia said. “So, our lab has really focused on trying to predict who will fall in this group.”

Melissa Oliver, MD, assistant professor of clinical pediatrics in the division of pediatric rheumatology at Indiana University in Indianapolis, was not involved in the study but agreed that having highly sensitive and specific biomarkers could be particularly helpful in clinical care.

“Biomarkers can help guide treatment decisions and help physicians and their patients share the decision-making about next choices and when to change,” Dr. Oliver told this news organization. “If a provider and parent know that their child has these markers in their serum or synovial fluid that may predict extension of their disease, then they may be more aggressive upfront with therapy.”

The study aimed to determine whether differential levels of synovial fluid proteins could be used to predict whether JIA would evolve into an extended course before it became clinically evident. Although early aggressive treatment is common with rheumatoid arthritis and can lead to remission, JIA treatment paradigms tend to be more reactive, Dr. Brescia said.

“It would be better to switch to proactive, that if we’re able to predict that this patient may have a more difficult course with extension to polyarticular, we could be prepared, we could inform the parents, and it would just help us have a more proactive approach,” she said.

The researchers used antibody arrays to detect the following inflammatory mediators in blinded samples: CD14, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, vascular endothelial growth factor (VEGF), and angiogenin. They analyzed 37 samples with persistent disease and 32 samples from disease that had not yet extended but would become extended in that patient. The samples came from patients who were taking no medicines or only NSAIDs. The researchers assessed the sensitivity and specificity of each biomarker. Sensitivity referred the biomarker’s ability to correctly indicate that the sample would extend, and specificity referred to the biomarker’s accuracy in determining that the disease in the sample would remain persistent.

Combining samples from cohorts at Nemours Children’s Health (14 persistent and 7 extended-to-be) and Cincinnati Children’s Hospital (23 persistent and 25 extended-to-be) yielded the following results:

“This is a work in progress,” Dr. Brescia said, “so hopefully you’ll hear about it next year.” In response to an attendee’s question, she said she believes identifying reliable biomarkers will eventually lead to refining treatment paradigms.

“I think it will at least change the guidance we can provide parents about making next choices and how quickly to accelerate to those next choices,” Dr. Brescia said. For example, if a child’s serum or synovial fluid has markers that show a very high likelihood of extension, the parent may decide to proceed to the next level medication sooner. “I do think it will push both parents and doctors to be a little more proactive instead of reactive when the poor patient comes back with 13 joints involved when they had just been an oligo for years.”

Dr. Oliver noted the promise of CD14 and IL-6 in potentially predicting which patients’ disease will stay persistent but cautioned that it’s still early in evaluating these biomarkers, especially with the limited patient samples in this study.

“I think these results are promising, and it’s great that there are groups out there working on this,” Dr. Oliver said. “Once we have a reliable, highly sensitive and specific biomarker, that will definitely help providers, parents, and patients be more informed.”

The research was supported by the Open Net Foundation, the Arthritis Foundation, Delaware Community Foundation, the Delaware Clinical and Translational Research (DE-CTR) ACCEL Program, the Nancy Taylor Foundation for Chronic Diseases, and CARRA. Dr. Brescia and Dr. Oliver have disclosed no relevant financial relationships.

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

Ongoing research in patients with oligoarticular juvenile idiopathic arthritis (JIA) so far suggests that a set of biomarkers in synovial fluid may help to predict which patients may be more likely to stay with persistent oligoarticular disease rather than progress to polyarticular disease, according to new research presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance, held virtually this year. Identifying biomarkers in synovial fluid or possibly serum could aid families and physicians in being more proactive in treatment protocols, said AnneMarie C. Brescia, MD, of Nemours Children’s Hospital in Wilmington, Del.

“JIA carries the risk of permanent joint damage and disability, which can result when joint involvement evolves from oligoarticular into a polyarticular course, termed extended oligoarticular disease,” Dr. Brescia told attendees. “Since disease progression increases the risk for disability, early prediction of this course is essential.”

This group – those whose oligoarticular disease will begin recruiting joints and ultimately become extended oligoarticular JIA – is “very important because they have been shown to have worse health-related quality of life and greater risk of needing a joint replacement than even polyarticular [JIA],” Dr. Brescia said. “So, our lab has really focused on trying to predict who will fall in this group.”

Melissa Oliver, MD, assistant professor of clinical pediatrics in the division of pediatric rheumatology at Indiana University in Indianapolis, was not involved in the study but agreed that having highly sensitive and specific biomarkers could be particularly helpful in clinical care.

“Biomarkers can help guide treatment decisions and help physicians and their patients share the decision-making about next choices and when to change,” Dr. Oliver told this news organization. “If a provider and parent know that their child has these markers in their serum or synovial fluid that may predict extension of their disease, then they may be more aggressive upfront with therapy.”

The study aimed to determine whether differential levels of synovial fluid proteins could be used to predict whether JIA would evolve into an extended course before it became clinically evident. Although early aggressive treatment is common with rheumatoid arthritis and can lead to remission, JIA treatment paradigms tend to be more reactive, Dr. Brescia said.

“It would be better to switch to proactive, that if we’re able to predict that this patient may have a more difficult course with extension to polyarticular, we could be prepared, we could inform the parents, and it would just help us have a more proactive approach,” she said.

The researchers used antibody arrays to detect the following inflammatory mediators in blinded samples: CD14, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, vascular endothelial growth factor (VEGF), and angiogenin. They analyzed 37 samples with persistent disease and 32 samples from disease that had not yet extended but would become extended in that patient. The samples came from patients who were taking no medicines or only NSAIDs. The researchers assessed the sensitivity and specificity of each biomarker. Sensitivity referred the biomarker’s ability to correctly indicate that the sample would extend, and specificity referred to the biomarker’s accuracy in determining that the disease in the sample would remain persistent.

Combining samples from cohorts at Nemours Children’s Health (14 persistent and 7 extended-to-be) and Cincinnati Children’s Hospital (23 persistent and 25 extended-to-be) yielded the following results:

“This is a work in progress,” Dr. Brescia said, “so hopefully you’ll hear about it next year.” In response to an attendee’s question, she said she believes identifying reliable biomarkers will eventually lead to refining treatment paradigms.

“I think it will at least change the guidance we can provide parents about making next choices and how quickly to accelerate to those next choices,” Dr. Brescia said. For example, if a child’s serum or synovial fluid has markers that show a very high likelihood of extension, the parent may decide to proceed to the next level medication sooner. “I do think it will push both parents and doctors to be a little more proactive instead of reactive when the poor patient comes back with 13 joints involved when they had just been an oligo for years.”

Dr. Oliver noted the promise of CD14 and IL-6 in potentially predicting which patients’ disease will stay persistent but cautioned that it’s still early in evaluating these biomarkers, especially with the limited patient samples in this study.

“I think these results are promising, and it’s great that there are groups out there working on this,” Dr. Oliver said. “Once we have a reliable, highly sensitive and specific biomarker, that will definitely help providers, parents, and patients be more informed.”

The research was supported by the Open Net Foundation, the Arthritis Foundation, Delaware Community Foundation, the Delaware Clinical and Translational Research (DE-CTR) ACCEL Program, the Nancy Taylor Foundation for Chronic Diseases, and CARRA. Dr. Brescia and Dr. Oliver have disclosed no relevant financial relationships.

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

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.