Vaccine recommendations for your patients with IBD

It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?

It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).

The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.

Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.

Give patients vaccine(s) for infections they are not immune as soon as possible.

Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
 

Help drive HCV testing, treatment, and eradication

AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.

Updates to QPP measure 400

In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.

The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.

Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.

Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.

Vaccine recommendations for your patients with IBD

It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?

It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).

The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.

Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.

Give patients vaccine(s) for infections they are not immune as soon as possible.

Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
 

Help drive HCV testing, treatment, and eradication

AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.

Updates to QPP measure 400

In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.

The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.

Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.

Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.

Vaccine recommendations for your patients with IBD

It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?

It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).

The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.

Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.

Give patients vaccine(s) for infections they are not immune as soon as possible.

Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
 

Help drive HCV testing, treatment, and eradication

AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.

Updates to QPP measure 400

In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.

The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.

Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.

Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.

In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.

“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
 

Two distinct subgroups

In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.

For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.

To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2.  After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
 

Weaker antitumor immune response

To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.

The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.

Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.

They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.

Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”

Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
 

Molecular subtyping offers better prognostic information

Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.

“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.

“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”

The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.

Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
 

New therapeutic targets

Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.

The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.

“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”

The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.

The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.

Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.

In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.

“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
 

Two distinct subgroups

In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.

For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.

To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2.  After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
 

Weaker antitumor immune response

To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.

The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.

Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.

They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.

Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”

Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
 

Molecular subtyping offers better prognostic information

Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.

“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.

“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”

The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.

Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
 

New therapeutic targets

Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.

The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.

“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”

The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.

The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.

Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.

In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.

“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
 

Two distinct subgroups

In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.

For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.

To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2.  After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
 

Weaker antitumor immune response

To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.

The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.

Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.

They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.

Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”

Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
 

Molecular subtyping offers better prognostic information

Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.

“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.

“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”

The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.

Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
 

New therapeutic targets

Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.

The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.

“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”

The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.

The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

Four major professional medical societies in the United States have called for urgent action to create a more sustainable model for digestive health care that decreases the environmental impact of gastroenterology practice, according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.

The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.

“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.

“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).

At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.

“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.

The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.

The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.

In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.

Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.

The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.

At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.

At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.

The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.

Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.

“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.

The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

In a gluten challenge trial, latiglutenase (IMGX003) reduced symptom severity and mucosal deterioration in patients with celiac disease, according to a new study published in Gastroenterology.

Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.

For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.

“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.

In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”

The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.

The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”

Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.

Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.

The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.

The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.

The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.

“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”

The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.

As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).

“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”

During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.

The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.

And of comprehending a response. But she was not given the opportunity.

“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”

Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said. 

For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”

Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.

Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.

When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.

“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”

More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.

Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
 

Don’t assume

The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”

Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?

“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”

Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”

Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.

Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”

Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”

One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”

And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.

Generation gap

Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.

Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.

“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”

Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.

As does Ms. Chin.

“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”

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

As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).

“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”

During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.

The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.

And of comprehending a response. But she was not given the opportunity.

“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”

Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said. 

For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”

Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.

Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.

When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.

“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”

More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.

Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
 

Don’t assume

The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”

Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?

“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”

Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”

Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.

Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”

Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”

One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”

And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.

Generation gap

Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.

Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.

“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”

Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.

As does Ms. Chin.

“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”

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

As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).

“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”

During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.

The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.

And of comprehending a response. But she was not given the opportunity.

“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”

Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said. 

For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”

Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.

Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.

When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.

“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”

More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.

Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
 

Don’t assume

The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”

Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?

“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”

Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”

Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.

Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”

Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”

One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”

And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.

Generation gap

Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.

Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.

“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”

Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.

As does Ms. Chin.

“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”

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

Don’t just sit there. Post something.

To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.

An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.

“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.

For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.

Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.

More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.

Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.

“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.

Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.

“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.

So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
 

How to create better content

While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.

“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”

More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.

First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.

“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.

The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.

Don’t just sit there. Post something.

To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.

An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.

“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.

For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.

Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.

More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.

Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.

“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.

Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.

“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.

So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
 

How to create better content

While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.

“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”

More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.

First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.

“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.

The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.

Don’t just sit there. Post something.

To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.

An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.

“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.

For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.

Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.

More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.

Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.

“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.

Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.

“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.

So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
 

How to create better content

While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.

“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”

More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.

First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.

“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.

The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.

The probability of spontaneous conversion to sinus rhythm (SCV) was increased with the intravenous administration of magnesium and potassium in patients with nonpermanent atrial fibrillation presenting to the ER, a registry study shows.

Compared with no treatment, potassium and magnesium administration was associated with a 10% higher rate of SVC.

The finding suggests that giving intravenous potassium and magnesium might lessen the need for antiarrhythmic therapy and the associated potential adverse effects in patients with nonpermanent atrial fibrillation (AFib), the study authors say.

Still, they add, “The results of our study have no direct implications for clinical practice in the management of care for patients with AF [atrial fibrillation] or AFL [atrial flutter] in the ED. The findings are purely exploratory and hypothesis-generating but could potentially provide a rationale for an appropriate prospective trial.”

The study was published online in JAMA Network Open.

“Atrial fibrillation is becoming an increasing burden for health care systems worldwide owing to population aging,” write Filippo Cacioppo, MD, and colleagues from Medical University of Vienna (Austria).

“Pharmacologic and electrical conversion are common therapies in emergency departments, especially for highly symptomatic patients. Each intervention has specific risks, and neither is considered cost-effective owing to frequent recurrence of AF. In addition, AF often terminates spontaneously,” Dr. Cacioppo and colleagues write.

They add that evidence suggests hypokalemia and hypomagnesemia contribute to AFib development, and so the administration of potassium and magnesium could be a reasonable strategy to improve SCV rates.

To test their hypothesis, Dr. Cacioppo and associates conducted a registry-based cohort study in all patients with AFib or AFL presenting to their center’s ED between Feb. 6, 2009, and Feb. 16, 2020.

During this time, they observed a total of 2,546 episodes of nonpermanent AFib. The median patient age was 68 years (interquartile range, 58-75 years). Most were men (n = 1,411 patients, 55.4%).

In addition, there were 573 episodes of nonpermanent AFL. The median patient age was 68 years (IQR, 58-75 years), and 332 patients (57.9%) were men.

Intravenous potassium and magnesium were administered in just over half (n = 1,763; 56.5%) of the episodes.

The median amount of potassium and magnesium was delivered via one 250-mL infusion bag, which consisted of 24 mEq potassium and 145.8 mg magnesium combined with 500 mL of balanced crystalloid fluid containing 2.5 mEq potassium and 18.2 mg magnesium, administered for 90 minutes, the authors write.

If patients experienced pain at the injection site, the infusion rate was reduced until the pain subsided.

Conversion to sinus rhythm was considered spontaneous if no attempt at pharmacologic rhythm control was made until conversion occurred; if SCV occurred after an unsuccessful attempt at electrical cardioversion; or following rate control with beta-blockers, nondihydropyridine calcium channel blockers, or digitalis glycosides, the authors state.
 

IV treatment increased odds of SCV

The median duration of stay in the ED was 6.4 hours (IQR, 3.9-11.6 hours) for patients with AFib and 6.1 hours (IQR, 3.9-11.8 hours) for patients with AFL.

During the stay in the ED, SCV occurred in 15.4% (n = 393) of AFib episodes and 12.7% (n = 73) of AFL episodes.

Intravenous potassium and magnesium increased the possibility of SCV compared with no IV potassium and magnesium in AFib, but not in AFL.

In episodes of AFib, administration of intravenous potassium and magnesium was associated with 19.2% increased odds of SCV, compared with 10.4% with no administration (odds ratio, 1.98; 95% CI, 1.53-2.57).

In contrast, for AFL, no association was observed for the probability of SCV with potassium and magnesium administration when compared with no administration (13.0% vs. 12.5%; OR, 1.05; 95% CI, 0.65-1.69).
 

Not in the guidelines

“To date, it is unclear whether potassium and magnesium administration might be reasonable in the acute treatment of AF and AFL, and although this intervention may be common practice in some EDs, it is not part of the treatment recommendations in current guidelines,” Dr. Cacioppo and colleagues write.

“Our findings suggest that intravenous potassium and magnesium administration may increase the chance of SCV in patients with AF with either hypokalemia or with plasma potassium levels in the range of 3.50 to 3.99 mEq/L. In patients with AFL, however, potassium and magnesium administration may not be associated with SCV probability,” they write.

Dr. Cacioppo and associates add that in their study IV administration of potassium and magnesium was associated with SCV only in patients with symptom onset of less than 48 hours, suggesting a time-dependent outcome. However, they caution, “because only a limited number of patients with SCV had symptom onset greater than or equal to 48 hours, this finding warrants further investigation.”
 

A Band-Aid approach

“I’m a little skeptical about this study,” Georgios Syros, MD, director of arrhythmia services at Mount Sinai Queens and Mount Sinai Brooklyn, New York, said in an interview.

“Atrial fibrillation is a chronic disease. The natural history of this disease is that it is paroxysmal in the beginning, and at some point the episodes become more frequent and longer in duration. For some people, at some point, it becomes permanent,” Dr. Syros said.

“Suppose I cut my finger while slicing bread. I put a Band-Aid on the cut. That doesn’t mean I have fixed it, it means I’ve helped it temporarily. Atrial fibrillation in this paper is very analogous,” he said. “The patient may have episodes, goes to the emergency room, you give them medication, and temporarily alleviate the situation so that the patient does not have to be admitted. It’s simple, inexpensive, you make the heart rate go back to normal, not permanently, with few side effects, except perhaps for some pain at the injection site, but that doesn’t mean you have fixed the AFib permanently. But for someone who has had a first incidence, or doesn’t want to stay in the hospital because it’s the weekend, yes, you can use this as a Band-Aid,” he said.

Intravenous potassium and magnesium, as proposed in the current study, is similar to a medication currently in use in Europe, called vernakalant, Dr. Syros said.

“Vernakalant is not FDA approved in the U.S. It is not meant to treat atrial fibrillation permanently, so we have to inform the public about the limitations of what we are doing,” he said. “Vernakalant is similar to IV potassium and magnesium, as given in this study, but it is more expensive. It temporarily allows people to go back to sinus rhythm, but it’s not going to be there forever and you may go back to permanent AFib, so this is not magic, unfortunately.”

Dr. Syros emphasized that the current study results apply only to cases of paroxysmal atrial fibrillation of less than 48 hours duration. “This is a very important distinction,” he said.

“For example, a patient who drank a lot and the day after is in AFib, with what we call holiday heart, would be a good candidate for the treatment in this study. He’s young, without any heart damage, no diabetes, no hypertension, no prior stroke, so sure, help him out with potassium and magnesium, provided that he can prove to us that this started within 48 hours,” Dr. Syros said.

Dr. Cacioppo and colleagues and Dr. Syros report no relevant financial relationships. Study corresponding author Jan Niederdoeckl, MD, PhD, obtained funding for the study.

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

The probability of spontaneous conversion to sinus rhythm (SCV) was increased with the intravenous administration of magnesium and potassium in patients with nonpermanent atrial fibrillation presenting to the ER, a registry study shows.

Compared with no treatment, potassium and magnesium administration was associated with a 10% higher rate of SVC.

The finding suggests that giving intravenous potassium and magnesium might lessen the need for antiarrhythmic therapy and the associated potential adverse effects in patients with nonpermanent atrial fibrillation (AFib), the study authors say.

Still, they add, “The results of our study have no direct implications for clinical practice in the management of care for patients with AF [atrial fibrillation] or AFL [atrial flutter] in the ED. The findings are purely exploratory and hypothesis-generating but could potentially provide a rationale for an appropriate prospective trial.”

The study was published online in JAMA Network Open.

“Atrial fibrillation is becoming an increasing burden for health care systems worldwide owing to population aging,” write Filippo Cacioppo, MD, and colleagues from Medical University of Vienna (Austria).

“Pharmacologic and electrical conversion are common therapies in emergency departments, especially for highly symptomatic patients. Each intervention has specific risks, and neither is considered cost-effective owing to frequent recurrence of AF. In addition, AF often terminates spontaneously,” Dr. Cacioppo and colleagues write.

They add that evidence suggests hypokalemia and hypomagnesemia contribute to AFib development, and so the administration of potassium and magnesium could be a reasonable strategy to improve SCV rates.

To test their hypothesis, Dr. Cacioppo and associates conducted a registry-based cohort study in all patients with AFib or AFL presenting to their center’s ED between Feb. 6, 2009, and Feb. 16, 2020.

During this time, they observed a total of 2,546 episodes of nonpermanent AFib. The median patient age was 68 years (interquartile range, 58-75 years). Most were men (n = 1,411 patients, 55.4%).

In addition, there were 573 episodes of nonpermanent AFL. The median patient age was 68 years (IQR, 58-75 years), and 332 patients (57.9%) were men.

Intravenous potassium and magnesium were administered in just over half (n = 1,763; 56.5%) of the episodes.

The median amount of potassium and magnesium was delivered via one 250-mL infusion bag, which consisted of 24 mEq potassium and 145.8 mg magnesium combined with 500 mL of balanced crystalloid fluid containing 2.5 mEq potassium and 18.2 mg magnesium, administered for 90 minutes, the authors write.

If patients experienced pain at the injection site, the infusion rate was reduced until the pain subsided.

Conversion to sinus rhythm was considered spontaneous if no attempt at pharmacologic rhythm control was made until conversion occurred; if SCV occurred after an unsuccessful attempt at electrical cardioversion; or following rate control with beta-blockers, nondihydropyridine calcium channel blockers, or digitalis glycosides, the authors state.
 

IV treatment increased odds of SCV

The median duration of stay in the ED was 6.4 hours (IQR, 3.9-11.6 hours) for patients with AFib and 6.1 hours (IQR, 3.9-11.8 hours) for patients with AFL.

During the stay in the ED, SCV occurred in 15.4% (n = 393) of AFib episodes and 12.7% (n = 73) of AFL episodes.

Intravenous potassium and magnesium increased the possibility of SCV compared with no IV potassium and magnesium in AFib, but not in AFL.

In episodes of AFib, administration of intravenous potassium and magnesium was associated with 19.2% increased odds of SCV, compared with 10.4% with no administration (odds ratio, 1.98; 95% CI, 1.53-2.57).

In contrast, for AFL, no association was observed for the probability of SCV with potassium and magnesium administration when compared with no administration (13.0% vs. 12.5%; OR, 1.05; 95% CI, 0.65-1.69).
 

Not in the guidelines

“To date, it is unclear whether potassium and magnesium administration might be reasonable in the acute treatment of AF and AFL, and although this intervention may be common practice in some EDs, it is not part of the treatment recommendations in current guidelines,” Dr. Cacioppo and colleagues write.

“Our findings suggest that intravenous potassium and magnesium administration may increase the chance of SCV in patients with AF with either hypokalemia or with plasma potassium levels in the range of 3.50 to 3.99 mEq/L. In patients with AFL, however, potassium and magnesium administration may not be associated with SCV probability,” they write.

Dr. Cacioppo and associates add that in their study IV administration of potassium and magnesium was associated with SCV only in patients with symptom onset of less than 48 hours, suggesting a time-dependent outcome. However, they caution, “because only a limited number of patients with SCV had symptom onset greater than or equal to 48 hours, this finding warrants further investigation.”
 

A Band-Aid approach

“I’m a little skeptical about this study,” Georgios Syros, MD, director of arrhythmia services at Mount Sinai Queens and Mount Sinai Brooklyn, New York, said in an interview.

“Atrial fibrillation is a chronic disease. The natural history of this disease is that it is paroxysmal in the beginning, and at some point the episodes become more frequent and longer in duration. For some people, at some point, it becomes permanent,” Dr. Syros said.

“Suppose I cut my finger while slicing bread. I put a Band-Aid on the cut. That doesn’t mean I have fixed it, it means I’ve helped it temporarily. Atrial fibrillation in this paper is very analogous,” he said. “The patient may have episodes, goes to the emergency room, you give them medication, and temporarily alleviate the situation so that the patient does not have to be admitted. It’s simple, inexpensive, you make the heart rate go back to normal, not permanently, with few side effects, except perhaps for some pain at the injection site, but that doesn’t mean you have fixed the AFib permanently. But for someone who has had a first incidence, or doesn’t want to stay in the hospital because it’s the weekend, yes, you can use this as a Band-Aid,” he said.

Intravenous potassium and magnesium, as proposed in the current study, is similar to a medication currently in use in Europe, called vernakalant, Dr. Syros said.

“Vernakalant is not FDA approved in the U.S. It is not meant to treat atrial fibrillation permanently, so we have to inform the public about the limitations of what we are doing,” he said. “Vernakalant is similar to IV potassium and magnesium, as given in this study, but it is more expensive. It temporarily allows people to go back to sinus rhythm, but it’s not going to be there forever and you may go back to permanent AFib, so this is not magic, unfortunately.”

Dr. Syros emphasized that the current study results apply only to cases of paroxysmal atrial fibrillation of less than 48 hours duration. “This is a very important distinction,” he said.

“For example, a patient who drank a lot and the day after is in AFib, with what we call holiday heart, would be a good candidate for the treatment in this study. He’s young, without any heart damage, no diabetes, no hypertension, no prior stroke, so sure, help him out with potassium and magnesium, provided that he can prove to us that this started within 48 hours,” Dr. Syros said.

Dr. Cacioppo and colleagues and Dr. Syros report no relevant financial relationships. Study corresponding author Jan Niederdoeckl, MD, PhD, obtained funding for the study.

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

The probability of spontaneous conversion to sinus rhythm (SCV) was increased with the intravenous administration of magnesium and potassium in patients with nonpermanent atrial fibrillation presenting to the ER, a registry study shows.

Compared with no treatment, potassium and magnesium administration was associated with a 10% higher rate of SVC.

The finding suggests that giving intravenous potassium and magnesium might lessen the need for antiarrhythmic therapy and the associated potential adverse effects in patients with nonpermanent atrial fibrillation (AFib), the study authors say.

Still, they add, “The results of our study have no direct implications for clinical practice in the management of care for patients with AF [atrial fibrillation] or AFL [atrial flutter] in the ED. The findings are purely exploratory and hypothesis-generating but could potentially provide a rationale for an appropriate prospective trial.”

The study was published online in JAMA Network Open.

“Atrial fibrillation is becoming an increasing burden for health care systems worldwide owing to population aging,” write Filippo Cacioppo, MD, and colleagues from Medical University of Vienna (Austria).

“Pharmacologic and electrical conversion are common therapies in emergency departments, especially for highly symptomatic patients. Each intervention has specific risks, and neither is considered cost-effective owing to frequent recurrence of AF. In addition, AF often terminates spontaneously,” Dr. Cacioppo and colleagues write.

They add that evidence suggests hypokalemia and hypomagnesemia contribute to AFib development, and so the administration of potassium and magnesium could be a reasonable strategy to improve SCV rates.

To test their hypothesis, Dr. Cacioppo and associates conducted a registry-based cohort study in all patients with AFib or AFL presenting to their center’s ED between Feb. 6, 2009, and Feb. 16, 2020.

During this time, they observed a total of 2,546 episodes of nonpermanent AFib. The median patient age was 68 years (interquartile range, 58-75 years). Most were men (n = 1,411 patients, 55.4%).

In addition, there were 573 episodes of nonpermanent AFL. The median patient age was 68 years (IQR, 58-75 years), and 332 patients (57.9%) were men.

Intravenous potassium and magnesium were administered in just over half (n = 1,763; 56.5%) of the episodes.

The median amount of potassium and magnesium was delivered via one 250-mL infusion bag, which consisted of 24 mEq potassium and 145.8 mg magnesium combined with 500 mL of balanced crystalloid fluid containing 2.5 mEq potassium and 18.2 mg magnesium, administered for 90 minutes, the authors write.

If patients experienced pain at the injection site, the infusion rate was reduced until the pain subsided.

Conversion to sinus rhythm was considered spontaneous if no attempt at pharmacologic rhythm control was made until conversion occurred; if SCV occurred after an unsuccessful attempt at electrical cardioversion; or following rate control with beta-blockers, nondihydropyridine calcium channel blockers, or digitalis glycosides, the authors state.
 

IV treatment increased odds of SCV

The median duration of stay in the ED was 6.4 hours (IQR, 3.9-11.6 hours) for patients with AFib and 6.1 hours (IQR, 3.9-11.8 hours) for patients with AFL.

During the stay in the ED, SCV occurred in 15.4% (n = 393) of AFib episodes and 12.7% (n = 73) of AFL episodes.

Intravenous potassium and magnesium increased the possibility of SCV compared with no IV potassium and magnesium in AFib, but not in AFL.

In episodes of AFib, administration of intravenous potassium and magnesium was associated with 19.2% increased odds of SCV, compared with 10.4% with no administration (odds ratio, 1.98; 95% CI, 1.53-2.57).

In contrast, for AFL, no association was observed for the probability of SCV with potassium and magnesium administration when compared with no administration (13.0% vs. 12.5%; OR, 1.05; 95% CI, 0.65-1.69).
 

Not in the guidelines

“To date, it is unclear whether potassium and magnesium administration might be reasonable in the acute treatment of AF and AFL, and although this intervention may be common practice in some EDs, it is not part of the treatment recommendations in current guidelines,” Dr. Cacioppo and colleagues write.

“Our findings suggest that intravenous potassium and magnesium administration may increase the chance of SCV in patients with AF with either hypokalemia or with plasma potassium levels in the range of 3.50 to 3.99 mEq/L. In patients with AFL, however, potassium and magnesium administration may not be associated with SCV probability,” they write.

Dr. Cacioppo and associates add that in their study IV administration of potassium and magnesium was associated with SCV only in patients with symptom onset of less than 48 hours, suggesting a time-dependent outcome. However, they caution, “because only a limited number of patients with SCV had symptom onset greater than or equal to 48 hours, this finding warrants further investigation.”
 

A Band-Aid approach

“I’m a little skeptical about this study,” Georgios Syros, MD, director of arrhythmia services at Mount Sinai Queens and Mount Sinai Brooklyn, New York, said in an interview.

“Atrial fibrillation is a chronic disease. The natural history of this disease is that it is paroxysmal in the beginning, and at some point the episodes become more frequent and longer in duration. For some people, at some point, it becomes permanent,” Dr. Syros said.

“Suppose I cut my finger while slicing bread. I put a Band-Aid on the cut. That doesn’t mean I have fixed it, it means I’ve helped it temporarily. Atrial fibrillation in this paper is very analogous,” he said. “The patient may have episodes, goes to the emergency room, you give them medication, and temporarily alleviate the situation so that the patient does not have to be admitted. It’s simple, inexpensive, you make the heart rate go back to normal, not permanently, with few side effects, except perhaps for some pain at the injection site, but that doesn’t mean you have fixed the AFib permanently. But for someone who has had a first incidence, or doesn’t want to stay in the hospital because it’s the weekend, yes, you can use this as a Band-Aid,” he said.

Intravenous potassium and magnesium, as proposed in the current study, is similar to a medication currently in use in Europe, called vernakalant, Dr. Syros said.

“Vernakalant is not FDA approved in the U.S. It is not meant to treat atrial fibrillation permanently, so we have to inform the public about the limitations of what we are doing,” he said. “Vernakalant is similar to IV potassium and magnesium, as given in this study, but it is more expensive. It temporarily allows people to go back to sinus rhythm, but it’s not going to be there forever and you may go back to permanent AFib, so this is not magic, unfortunately.”

Dr. Syros emphasized that the current study results apply only to cases of paroxysmal atrial fibrillation of less than 48 hours duration. “This is a very important distinction,” he said.

“For example, a patient who drank a lot and the day after is in AFib, with what we call holiday heart, would be a good candidate for the treatment in this study. He’s young, without any heart damage, no diabetes, no hypertension, no prior stroke, so sure, help him out with potassium and magnesium, provided that he can prove to us that this started within 48 hours,” Dr. Syros said.

Dr. Cacioppo and colleagues and Dr. Syros report no relevant financial relationships. Study corresponding author Jan Niederdoeckl, MD, PhD, obtained funding for the study.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Falls are common in patients with multiple sclerosis (MS) and a new study suggests impairment in a specific aspect of neuromuscular function can identify those at highest risk. Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.

“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.

The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Explosive strength

In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.

“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.

Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.

To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.

Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.

A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.

At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.

There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.

He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
 

‘Highly promising’ approach

“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.

This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.

“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.

More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.

“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.

The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.

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

Falls are common in patients with multiple sclerosis (MS) and a new study suggests impairment in a specific aspect of neuromuscular function can identify those at highest risk. Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.

“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.

The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Explosive strength

In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.

“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.

Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.

To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.

Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.

A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.

At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.

There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.

He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
 

‘Highly promising’ approach

“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.

This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.

“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.

More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.

“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.

The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.

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

Falls are common in patients with multiple sclerosis (MS) and a new study suggests impairment in a specific aspect of neuromuscular function can identify those at highest risk. Compared with patients with MS who didn’t fall, those who did fall had worse neuromuscular function as evidenced by a reduced rate of force development.

“Our study suggests that instead of looking at reduced maximum muscle strength, perhaps we should start looking at reduced rate of force development when trying to identify potential fallers,” said Laurits Taul-Madsen, PhD student, Aarhus University, Denmark.

The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Explosive strength

In contrast to maximal muscle strength, the rate of force development is a measure of explosive strength, or simply the amount of force that an individual can produce over a given time period. When a patient is about to fall, what’s most important is not how strong the person is, but how quickly they can produce enough force to counteract the balance perturbation, thus avoid falling, said Dr. Taul-Madsen.

“If a person is very slow to produce this force, [that person] will have fallen before he or she has produced enough force to counteract the balance perturbation that the person is experiencing,” he added.

Research has shown a reduced rate of force development (RFD) in patients with MS, compared with healthy controls. However, little is known about the impact of RFD on falls in those with MS.

To investigate, researchers studied 53 adults with MS: Twenty-four had no fall history in the prior year, 16 had one to two prior falls, and 13 had three or more falls. The two groups of fallers were both slightly older and had a slightly higher Expanded Disability Status Scale (EDSS) scores, “which may not be so surprising,” Dr. Taul-Madsen said.

Knee extensor neuromuscular function, including maximum muscle strength and RFD at 50 and 200 milliseconds, was assessed via isokinetic dynamometry.

A high RFD is “good and the non-fallers had the highest RFD at 50 ms.” On this measure, “we saw quite a big difference between the non-fallers and the two groups of fallers,” Dr. Taul-Madsen reported.

At 200 ms, the RFD was again highest in the group of non-fallers but the difference was somewhat smaller. Non-fallers also had greater maximum muscle strength than that of the fallers.

There was “good” correlation between these neuromuscular measurements and falls, Dr. Taul-Madsen said.

He noted that RFD, which can be improved with resistance training, “seems like a specialized and difficult measurement, but it doesn’t have to be. It can be measured with just a linear encoder and a chair to perform the sit-to-stand test, so in clinical practice, it’s quite easily measured.”
 

‘Highly promising’ approach

“There are some data on predictors of falls in persons with MS, but not yet on neuromuscular function, as has been done in other populations,” said Brian Sandroff, PhD, senior research scientist, Kessler Foundation, West Orange, N.J.

This study is “interesting in that recurrent fallers were distinguished based on having worse neuromuscular function,” said Dr. Sandroff, who was not part of the research team.

“Although this relationship is somewhat intuitive,” RFD provides a “potentially sensitive measure that can be addressed via specific resistance exercise programs as a highly promising approach for reducing fall risk and falls themselves in persons with MS,” Dr. Sandroff said.

More generally, he said this study provides “more evidence on the multisystemic benefits of exercise training and having better physical fitness in persons with MS.

“The evidence seems to be converging more and more on this, as research groups across countries and continents are reporting on similar themes,” said Dr. Sandroff.

The study had no specific funding. Dr. Taul-Madsen and Dr. Sandroff report no relevant financial relationships.

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