Guidelines

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

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

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

As researchers learn more about the genetic etiology of immunopathology, they have been able to more clearly understand rare but debilitating autoinflammatory conditions in ways that have improved identification and management of these diseases. At this year’s European Congress of Rheumatology, two researchers outlined new recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) for the management of two groups of such autoinflammatory diseases: interleukin-1-mediated and Type-I interferonopathies, and suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

These are the first recommendations from EULAR for these diseases, according to Loreto Carmona, MD, PhD, chair of the EULAR scientific program committee and scientific director of the Institute for Musculoskeletal Health in Madrid.

“They are rare diseases and there is a great need to standardize diagnosis and care for the safety and outcome of the patients,” Dr. Carmona said in an interview. “These diseases need deep expertise and so the experts are trying, they are still preliminary, to add clarity to their management.” Dr. Carmona was not involved with the development of the guidelines and moderated the session during which they were presented.

“The rapidly emerging knowledge of the genetic causes of novel systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, linked the disease pathogenesis to the pathologic production of major proinflammatory cytokines,” presenter Raphaela Goldbach-Mansky, MD, a senior investigator and chief of the translational autoinflammatory disease studies unit of the U.S. National Institute of Allergy and Infectious Diseases, told congress attendees. This greater understanding led to the “targeted and anticytokine treatments that have changed patients’ lives,” she said.

The guidelines relied on the products of three working groups for each disease type. After meeting to come up with clinical questions, the groups each conducted systematic literature reviews through EMBASE, PubMed, and the Cochrane Library for publications dated from 1970 to August 2020 that excluded non-English-language studies, case reports, and animal model or basic science studies. They then met again to develop final consensus statements.

The interferonopathy and interleukin (IL)-1-mediated systemic autoinflammatory diseases (SAIDs) working groups met throughout 2020, and the hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) working group met in March and April of 2021.

“One needs a lot of experience with these diseases to even think about them,” Dr. Carmona said. “We haven’t been presented yet with all the details of the recommendations, but we hope they are clear because they are much needed.”

She noted that these preliminary recommendations are based on the best available evidence to date along with expertise from multidisciplinary panels.

“We need to be acquainted with these recommendations, as the majority of us, either if we are pediatric or adult rheumatologists, will face some problem with these diseases at some point,” Dr. Carmona said.

IL-1-mediated SAIDs

Recommendations for IL-1-mediated SAIDs focused on mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA). Presentation of these conditions involves chronic or intermittent flares of systemic and organ inflammation that can cause progressive organ damage, morbidity, and increased mortality if not treated. Diagnosis requires a multidisciplinary team whose evaluation should include disease-related complications and long-term care plans.

Diagnostic workup should include genetic testing using next-generation sequencing as this “facilitates initiation of targeted treatments, genetic counseling, and informs prognosis” for patients with CAPS, TRAPS, MKD, and DIRA, Erkan Demirkaya, MD, a scientist at the Children’s Health Research Institute and professor of pediatric rheumatology at the University of Western Ontario in London, Canada, told attendees. Evaluation should also include clinical workup that focuses on the extent of inflammatory organ involvement, and screening for disease- and treatment-related comorbidities.

“The goal of therapy is to control clinical signs and symptoms and normalize laboratory biomarkers of systemic inflammation,” Dr. Demirkaya said. Long-term monitoring goals should focus on the following:

• “Adequate treatment adjusted to the needs of the growing child and prevention of systemic and organ-specific inflammatory manifestations;
• Fostering of self-management skills and medical decision-making;
• Initiating a transition program to adult specialist care in adolescent patients.”

Type-1 interferonopathies

The recommendations for this disease group focused on chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)/proteasome-associated autoinflammatory syndromes (PRAAS), STING-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS).

These patients similarly present with chronic and organ-specific inflammation that leads to progressive organ damage, morbidity, and higher mortality risk when not managed. Each of these diseases requires a confirmed genetic diagnosis so that treatments can be targeted and the patient receives appropriate genetic counseling, screening for complications, and information on prognosis, Dr. Goldbach-Mansky said.

Treatment goals for type-1 interferonopathies are to “reduce systematic and organ inflammation to prevent or limit the development of progression of organ injury or damage and to improve quality of life,” Dr. Goldbach-Mansky told attendees.

Each patient requires a multidisciplinary care provider team that conducts long-term monitoring of disease activity, damage to specific organs, and any treatment-related complications.
 

Management of HLH/MAS

Early recognition and management of HLH and MAS can be challenging because systemic hyperinflammation exists along an immunopathologic continuum with typically nonspecific clinical and laboratory findings, Dr. Goldbach-Mansky said, but holistic, longitudinal consideration of these findings “are recognizable and warrant prompt diagnostic evaluation.” Even if the patient does not meet all specific diagnostic criteria for HLH/MAS, it may be necessary to begin therapies, she said.

One important point to consider is that “systemic hyperinflammation can be associated with hyperferritinemia and can progress to life-threatening HLH/MAS,” Dr. Goldbach-Mansky said. Further, although “systemic hyperinflammation and HLH/MAS can occur in nearly any inflammatory state,” certain common triggers and predisposing conditions can indicate the need to consider these conditions and begin appropriate treatment if needed. Part of effective management of systemic hyperinflammation and HLH/MAS is determining any modifiable factors contributing to the disease and mitigating or treating those.

HLH/MAS requires urgent intervention based on the patient’s degree of inflammation and extent of organ dysfunction, the recommendations state. Treatment goals include preventing or limiting immunopathology, preserving the integrity of the diagnostic workup, and minimizing therapy-related toxicity.

Dr. Carmona, Dr. Goldbach-Mansky, and Dr. Demirkaya have reported no relevant financial relationships.


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

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

The European Alliance of Associations for Rheumatology has started the process of updating their recommendations on how to manage patients with rheumatic and musculoskeletal diseases (RMDs) in the context of the SARS-CoV-2 pandemic.

So far, the first part of the systematic literature review has been performed and the conclusions that have been drawn appear to back up the recommendations that have already been made. It’s “hard to say” if there will need to be changes, said Robert B.M. Landewé, MD, PhD, at the annual European Congress of Rheumatology, as the next phase will be for the task force members to meet and discuss the implications of the literature research.“I think there will only be minor modifications and a few novel recommendations, but that is personal opinion,” speculated Dr. Landewé, who is professor of rheumatology at the Amsterdam Medical Center, University of Amsterdam.

The recommendations, which were developed a little over a year ago and published in Annals of the Rheumatic Diseases, set out provisional guidance covering four themes: infection prevention, managing patients when social distancing measures are in effect, managing patients with RMDs who develop COVID-19, and the prevention of infections other than SARS-CoV-2.
 

Emphasis on quality of evidence

According to EULAR’s standard operating procedures “updates should only be done if the evolving evidence mandates to do so,” and be based on “rational arguments,” Dr. Landewé said. “The last year was a bit unprecedented in that regard as we didn’t have those rational arguments before we designed our first set of recommendations and, as you can expect, that is totally due to the character of the pandemic.”

So much has been published on COVID-19 since then it was time to reappraise the situation. The task force behind the recommendations met in January 2021 to discuss the results of the literature search that was centered around five main research questions.

• Do patients with RMDs face more risk of contracting SARS-CoV-2 than the general population?
• If patients contract the virus, do they have a worse prognosis?
• Are antirheumatic medications associated with a worse outcome in people with RMDs?
• Should patients continue their antirheumatic medications?
• What evidence informs the use of vaccination against SARS-CoV-2 in patients with RMDs?

The latter research question is pending discussion since there were no studies to review at the time as the various vaccines had only just started to be widely available.

“We put a lot of emphasis on the quality of evidence,” Dr. Landewé said. In addition to making sure that patients did indeed have COVID-19 and checking that hospitalization and death records were caused by the disease, the task force team also looked to see if there was a control group being used. An extensive risk of bias assessment was undertaken, the results of which are pending.

Of 6,665 records identified during the literature search, just 113 full-text articles were assessed for eligibility. Of those, 60% were rejected as they did not pass the quality assessment, leaving 49 articles for consideration. The majority of these looked at the incidence of COVID-19, with others focusing on risk factors or both.
 

Literature search findings on main research questions

Dr. Landewé observed that the task force concluded that “current literature provides no evidence that patients with RMDs face more risk of contracting SARS-CoV-2 than individuals without RMDs.” They also concluded that patients with RMDs who do contract COVID-19 do not have a worse prognosis either, even though there have been a few studies suggesting a higher rate of hospitalization.

Both findings are reassuring as they fit with the existing recommendation to follow the same preventive and control measures in patients with RMDs as for the general population, but the task force is yet to determine if that recommendation should be amended.

There did not appear to be any hard evidence of any unique demographic feature or comorbidity that puts people with RMDs at more risk for severe COVID-19 than the general population. Think older age, male gender, high bodyweight, cardiovascular disease, diabetes, and chronic lung disease, Dr. Landewé said.

He noted, however, that there were some single-center reports suggesting that moderate or high levels of disease activity could put people with RMDs at greater risk for COVID-related death, “which is an intriguing finding in the context of discontinuing antirheumatic medication.” That is likely something the task force will be discussing when they decide how to update their recommendations.

The type of RMD may also be important, but again only single-center evidence to show that there might be an increased hospitalization risk in patients with autoinflammatory disease or risk for severe COVID-19 in those with certain connective tissue diseases. “These associations were not consistently found in other studies,” so it’s an open question how the task force decides to incorporate this into the updated guidance.

As for antirheumatic medications, conclusions from the literature review suggest that there doesn’t appear to be an increased or decreased risk for severe COVID-19 among users of NSAIDs or antimalarials.

That’s not the case for glucocorticoids. There appears to be an increased risk for hospitalization and COVID-19–related death, notably among those using higher (>10 mg) daily doses. “This is, so to say, the elephant in the room,” Dr. Landewé said. The current recommendation states that chronic users of glucocorticoids should continue their treatment. “The reports of additional risk could be due to glucocorticoids or to biases such as confounding by indication. So, the conclusion that we draw [is] not completely clear.”

In response to a question, he clarified this a little further: “We think ‘glucocorticoid use’ is a determinant of worse health, as is the case in many RMDs. Be aware that finding a positive association between [glucocorticoid] use and bad outcome does not mean that if you reduce [glucocorticoids], your patient will have a better outcome.”

The jury is also out on rituximab, which has been reported to increase the risk of severe COVID-19 and COVID-related death in two studies. There are also equivocal data on whether not using disease-modifying antirheumatic drugs increases the risk for these worse outcomes.

Asked about the absence of a recommendation on the use of the interleukin-6 inhibitor tocilizumab, Dr. Landewé responded: “We are caught up by evolving evidence. That is a generic problem in a dynamic field of COVID-19, I am afraid. What you recommend today is sometimes ‘old history’ tomorrow.”

Dr. Landewé had no relevant disclosures to make.

The European Alliance of Associations for Rheumatology has started the process of updating their recommendations on how to manage patients with rheumatic and musculoskeletal diseases (RMDs) in the context of the SARS-CoV-2 pandemic.

So far, the first part of the systematic literature review has been performed and the conclusions that have been drawn appear to back up the recommendations that have already been made. It’s “hard to say” if there will need to be changes, said Robert B.M. Landewé, MD, PhD, at the annual European Congress of Rheumatology, as the next phase will be for the task force members to meet and discuss the implications of the literature research.“I think there will only be minor modifications and a few novel recommendations, but that is personal opinion,” speculated Dr. Landewé, who is professor of rheumatology at the Amsterdam Medical Center, University of Amsterdam.

The recommendations, which were developed a little over a year ago and published in Annals of the Rheumatic Diseases, set out provisional guidance covering four themes: infection prevention, managing patients when social distancing measures are in effect, managing patients with RMDs who develop COVID-19, and the prevention of infections other than SARS-CoV-2.
 

Emphasis on quality of evidence

According to EULAR’s standard operating procedures “updates should only be done if the evolving evidence mandates to do so,” and be based on “rational arguments,” Dr. Landewé said. “The last year was a bit unprecedented in that regard as we didn’t have those rational arguments before we designed our first set of recommendations and, as you can expect, that is totally due to the character of the pandemic.”

So much has been published on COVID-19 since then it was time to reappraise the situation. The task force behind the recommendations met in January 2021 to discuss the results of the literature search that was centered around five main research questions.

• Do patients with RMDs face more risk of contracting SARS-CoV-2 than the general population?
• If patients contract the virus, do they have a worse prognosis?
• Are antirheumatic medications associated with a worse outcome in people with RMDs?
• Should patients continue their antirheumatic medications?
• What evidence informs the use of vaccination against SARS-CoV-2 in patients with RMDs?

The latter research question is pending discussion since there were no studies to review at the time as the various vaccines had only just started to be widely available.

“We put a lot of emphasis on the quality of evidence,” Dr. Landewé said. In addition to making sure that patients did indeed have COVID-19 and checking that hospitalization and death records were caused by the disease, the task force team also looked to see if there was a control group being used. An extensive risk of bias assessment was undertaken, the results of which are pending.

Of 6,665 records identified during the literature search, just 113 full-text articles were assessed for eligibility. Of those, 60% were rejected as they did not pass the quality assessment, leaving 49 articles for consideration. The majority of these looked at the incidence of COVID-19, with others focusing on risk factors or both.
 

Literature search findings on main research questions

Dr. Landewé observed that the task force concluded that “current literature provides no evidence that patients with RMDs face more risk of contracting SARS-CoV-2 than individuals without RMDs.” They also concluded that patients with RMDs who do contract COVID-19 do not have a worse prognosis either, even though there have been a few studies suggesting a higher rate of hospitalization.

Both findings are reassuring as they fit with the existing recommendation to follow the same preventive and control measures in patients with RMDs as for the general population, but the task force is yet to determine if that recommendation should be amended.

There did not appear to be any hard evidence of any unique demographic feature or comorbidity that puts people with RMDs at more risk for severe COVID-19 than the general population. Think older age, male gender, high bodyweight, cardiovascular disease, diabetes, and chronic lung disease, Dr. Landewé said.

He noted, however, that there were some single-center reports suggesting that moderate or high levels of disease activity could put people with RMDs at greater risk for COVID-related death, “which is an intriguing finding in the context of discontinuing antirheumatic medication.” That is likely something the task force will be discussing when they decide how to update their recommendations.

The type of RMD may also be important, but again only single-center evidence to show that there might be an increased hospitalization risk in patients with autoinflammatory disease or risk for severe COVID-19 in those with certain connective tissue diseases. “These associations were not consistently found in other studies,” so it’s an open question how the task force decides to incorporate this into the updated guidance.

As for antirheumatic medications, conclusions from the literature review suggest that there doesn’t appear to be an increased or decreased risk for severe COVID-19 among users of NSAIDs or antimalarials.

That’s not the case for glucocorticoids. There appears to be an increased risk for hospitalization and COVID-19–related death, notably among those using higher (>10 mg) daily doses. “This is, so to say, the elephant in the room,” Dr. Landewé said. The current recommendation states that chronic users of glucocorticoids should continue their treatment. “The reports of additional risk could be due to glucocorticoids or to biases such as confounding by indication. So, the conclusion that we draw [is] not completely clear.”

In response to a question, he clarified this a little further: “We think ‘glucocorticoid use’ is a determinant of worse health, as is the case in many RMDs. Be aware that finding a positive association between [glucocorticoid] use and bad outcome does not mean that if you reduce [glucocorticoids], your patient will have a better outcome.”

The jury is also out on rituximab, which has been reported to increase the risk of severe COVID-19 and COVID-related death in two studies. There are also equivocal data on whether not using disease-modifying antirheumatic drugs increases the risk for these worse outcomes.

Asked about the absence of a recommendation on the use of the interleukin-6 inhibitor tocilizumab, Dr. Landewé responded: “We are caught up by evolving evidence. That is a generic problem in a dynamic field of COVID-19, I am afraid. What you recommend today is sometimes ‘old history’ tomorrow.”

Dr. Landewé had no relevant disclosures to make.

The European Alliance of Associations for Rheumatology has started the process of updating their recommendations on how to manage patients with rheumatic and musculoskeletal diseases (RMDs) in the context of the SARS-CoV-2 pandemic.

So far, the first part of the systematic literature review has been performed and the conclusions that have been drawn appear to back up the recommendations that have already been made. It’s “hard to say” if there will need to be changes, said Robert B.M. Landewé, MD, PhD, at the annual European Congress of Rheumatology, as the next phase will be for the task force members to meet and discuss the implications of the literature research.“I think there will only be minor modifications and a few novel recommendations, but that is personal opinion,” speculated Dr. Landewé, who is professor of rheumatology at the Amsterdam Medical Center, University of Amsterdam.

The recommendations, which were developed a little over a year ago and published in Annals of the Rheumatic Diseases, set out provisional guidance covering four themes: infection prevention, managing patients when social distancing measures are in effect, managing patients with RMDs who develop COVID-19, and the prevention of infections other than SARS-CoV-2.
 

Emphasis on quality of evidence

According to EULAR’s standard operating procedures “updates should only be done if the evolving evidence mandates to do so,” and be based on “rational arguments,” Dr. Landewé said. “The last year was a bit unprecedented in that regard as we didn’t have those rational arguments before we designed our first set of recommendations and, as you can expect, that is totally due to the character of the pandemic.”

So much has been published on COVID-19 since then it was time to reappraise the situation. The task force behind the recommendations met in January 2021 to discuss the results of the literature search that was centered around five main research questions.

• Do patients with RMDs face more risk of contracting SARS-CoV-2 than the general population?
• If patients contract the virus, do they have a worse prognosis?
• Are antirheumatic medications associated with a worse outcome in people with RMDs?
• Should patients continue their antirheumatic medications?
• What evidence informs the use of vaccination against SARS-CoV-2 in patients with RMDs?

The latter research question is pending discussion since there were no studies to review at the time as the various vaccines had only just started to be widely available.

“We put a lot of emphasis on the quality of evidence,” Dr. Landewé said. In addition to making sure that patients did indeed have COVID-19 and checking that hospitalization and death records were caused by the disease, the task force team also looked to see if there was a control group being used. An extensive risk of bias assessment was undertaken, the results of which are pending.

Of 6,665 records identified during the literature search, just 113 full-text articles were assessed for eligibility. Of those, 60% were rejected as they did not pass the quality assessment, leaving 49 articles for consideration. The majority of these looked at the incidence of COVID-19, with others focusing on risk factors or both.
 

Literature search findings on main research questions

Dr. Landewé observed that the task force concluded that “current literature provides no evidence that patients with RMDs face more risk of contracting SARS-CoV-2 than individuals without RMDs.” They also concluded that patients with RMDs who do contract COVID-19 do not have a worse prognosis either, even though there have been a few studies suggesting a higher rate of hospitalization.

Both findings are reassuring as they fit with the existing recommendation to follow the same preventive and control measures in patients with RMDs as for the general population, but the task force is yet to determine if that recommendation should be amended.

There did not appear to be any hard evidence of any unique demographic feature or comorbidity that puts people with RMDs at more risk for severe COVID-19 than the general population. Think older age, male gender, high bodyweight, cardiovascular disease, diabetes, and chronic lung disease, Dr. Landewé said.

He noted, however, that there were some single-center reports suggesting that moderate or high levels of disease activity could put people with RMDs at greater risk for COVID-related death, “which is an intriguing finding in the context of discontinuing antirheumatic medication.” That is likely something the task force will be discussing when they decide how to update their recommendations.

The type of RMD may also be important, but again only single-center evidence to show that there might be an increased hospitalization risk in patients with autoinflammatory disease or risk for severe COVID-19 in those with certain connective tissue diseases. “These associations were not consistently found in other studies,” so it’s an open question how the task force decides to incorporate this into the updated guidance.

As for antirheumatic medications, conclusions from the literature review suggest that there doesn’t appear to be an increased or decreased risk for severe COVID-19 among users of NSAIDs or antimalarials.

That’s not the case for glucocorticoids. There appears to be an increased risk for hospitalization and COVID-19–related death, notably among those using higher (>10 mg) daily doses. “This is, so to say, the elephant in the room,” Dr. Landewé said. The current recommendation states that chronic users of glucocorticoids should continue their treatment. “The reports of additional risk could be due to glucocorticoids or to biases such as confounding by indication. So, the conclusion that we draw [is] not completely clear.”

In response to a question, he clarified this a little further: “We think ‘glucocorticoid use’ is a determinant of worse health, as is the case in many RMDs. Be aware that finding a positive association between [glucocorticoid] use and bad outcome does not mean that if you reduce [glucocorticoids], your patient will have a better outcome.”

The jury is also out on rituximab, which has been reported to increase the risk of severe COVID-19 and COVID-related death in two studies. There are also equivocal data on whether not using disease-modifying antirheumatic drugs increases the risk for these worse outcomes.

Asked about the absence of a recommendation on the use of the interleukin-6 inhibitor tocilizumab, Dr. Landewé responded: “We are caught up by evolving evidence. That is a generic problem in a dynamic field of COVID-19, I am afraid. What you recommend today is sometimes ‘old history’ tomorrow.”

Dr. Landewé had no relevant disclosures to make.

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

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

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

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

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

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

When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.

“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.

“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.

The updated guideline was published online May 24, 2021, in Stroke.

“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.

The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
 

Let pathogenic subtype guide prevention

For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.

Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.

“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.

For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.

Among the recommendations:

• Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
• Screen for  and initiate anticoagulant drug therapy to reduce recurrent events.
• Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking  along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
• Consider  or carotid artery stenting for select patients with narrowing of carotid arteries.
• Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
• In some patients, it’s reasonable to consider percutaneous closure of .

The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.

“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.

The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.

The research had no commercial funding.

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

When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.

“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.

“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.

The updated guideline was published online May 24, 2021, in Stroke.

“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.

The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
 

Let pathogenic subtype guide prevention

For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.

Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.

“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.

For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.

Among the recommendations:

• Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
• Screen for  and initiate anticoagulant drug therapy to reduce recurrent events.
• Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking  along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
• Consider  or carotid artery stenting for select patients with narrowing of carotid arteries.
• Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
• In some patients, it’s reasonable to consider percutaneous closure of .

The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.

“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.

The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.

The research had no commercial funding.

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

When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.

“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.

“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.

The updated guideline was published online May 24, 2021, in Stroke.

“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.

The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
 

Let pathogenic subtype guide prevention

For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.

Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.

“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.

For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.

Among the recommendations:

• Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
• Screen for  and initiate anticoagulant drug therapy to reduce recurrent events.
• Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking  along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
• Consider  or carotid artery stenting for select patients with narrowing of carotid arteries.
• Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
• In some patients, it’s reasonable to consider percutaneous closure of .

The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.

“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.

The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.

The research had no commercial funding.

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