Guidelines

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2023.

In a policy statement published online in the journal Pediatrics, the AAP said the updated recommendations do not include major changes from those released in 2022 by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

In one small shift, COVID-19 is now addressed in the main text instead of being relegated to the notes section.

“And a new vaccine – Priorix [GlaxoSmithKline] – has been added for MMR [measles, mumps, rubella], so now there are two available,” Sean T. O’Leary, MD, MPH, chair of the AAP’s Committee on Infectious Diseases, told this news organization. “There’s also a second pneumococcal conjugate vaccine listed, PCV15, and this and PCV13 can essentially be used interchangeably.”

Minor updates to the schedule, reflected on the cover page, relate to vaccines for COVID-19, dengue fever, and pneumococcal disease, added Dr. O’Leary, a professor of pediatrics at the University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora.

The committee also changed layouts to improve the usability of the schedule. Updated annually, the guidance provides a table on recommended pediatric immunizations from birth to age 18 years, and catch-up recommendations for children aged 4 months to 18 years who start their vaccinations late or are more than 1 month behind the recommended age for vaccine administration.

“We hope this annual update will encourage clinicians to make sure all their patients are up to date on their routine vaccinations,” Dr. O’Leary said. “It’s an opportunity to develop strategies to improve vaccination rates.”

The 2023 schedule follows news from the CDC that kindergarten vaccination rates declined during the 2021-2022 school year. Only 93% of kindergarteners obtained full vaccinations, representing a drop of 1 percentage point from the year before and 2 percentage points from the 2019-2020 school year.

The dip in coverage has been attributed to disruptions caused by the COVID-19 pandemic. AAP advises health care professionals to urge families to make sure their child’s vaccines are current.

Among other additions:
 

In Table 1

• MMR: Second vaccine added (Priorix, GlaxoSmithKline Biologicals)
• Pneumococcal disease: second conjugate vaccine, PCV15, added (Vaxneuvance, Merck Sharp & Dohme).
• COVID-19: New row added.
• Dengue: Text changed from “Seropositive in endemic areas only” to “Seropositive in endemic dengue areas.”
• Inactivated polio vaccine: “See Notes” added to the column for children aged 18 years.

In Table 2

• PCV: Dose 3 to dose 4 interval revised to align with ACIP’s recommendation for dose 4. This dose is necessary only for children ages 12-59 months regardless of risk, or age 60-71 months with any risk who received three doses before age 12 months.

A parent-friendly vaccine schedule for children and adolescents is available on the CDC’s website.

“Vaccines are essential for the health of our whole society, including children and adolescents,” Dr. O’Leary said in a press release from AAP. “These schedules provide a road map [that] parents and pediatricians can follow to help children get the vaccines they need so their immune systems will be ready to recognize and resist diseases.”

As previously, the 2023 schedule was adjusted to ensure consistency between the formats of the childhood/adolescent and adult immunization guidance. A meeting of stakeholder organizations in October 2022 harmonized the two formats.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2023.

In a policy statement published online in the journal Pediatrics, the AAP said the updated recommendations do not include major changes from those released in 2022 by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

In one small shift, COVID-19 is now addressed in the main text instead of being relegated to the notes section.

“And a new vaccine – Priorix [GlaxoSmithKline] – has been added for MMR [measles, mumps, rubella], so now there are two available,” Sean T. O’Leary, MD, MPH, chair of the AAP’s Committee on Infectious Diseases, told this news organization. “There’s also a second pneumococcal conjugate vaccine listed, PCV15, and this and PCV13 can essentially be used interchangeably.”

Minor updates to the schedule, reflected on the cover page, relate to vaccines for COVID-19, dengue fever, and pneumococcal disease, added Dr. O’Leary, a professor of pediatrics at the University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora.

The committee also changed layouts to improve the usability of the schedule. Updated annually, the guidance provides a table on recommended pediatric immunizations from birth to age 18 years, and catch-up recommendations for children aged 4 months to 18 years who start their vaccinations late or are more than 1 month behind the recommended age for vaccine administration.

“We hope this annual update will encourage clinicians to make sure all their patients are up to date on their routine vaccinations,” Dr. O’Leary said. “It’s an opportunity to develop strategies to improve vaccination rates.”

The 2023 schedule follows news from the CDC that kindergarten vaccination rates declined during the 2021-2022 school year. Only 93% of kindergarteners obtained full vaccinations, representing a drop of 1 percentage point from the year before and 2 percentage points from the 2019-2020 school year.

The dip in coverage has been attributed to disruptions caused by the COVID-19 pandemic. AAP advises health care professionals to urge families to make sure their child’s vaccines are current.

Among other additions:
 

In Table 1

• MMR: Second vaccine added (Priorix, GlaxoSmithKline Biologicals)
• Pneumococcal disease: second conjugate vaccine, PCV15, added (Vaxneuvance, Merck Sharp & Dohme).
• COVID-19: New row added.
• Dengue: Text changed from “Seropositive in endemic areas only” to “Seropositive in endemic dengue areas.”
• Inactivated polio vaccine: “See Notes” added to the column for children aged 18 years.

In Table 2

• PCV: Dose 3 to dose 4 interval revised to align with ACIP’s recommendation for dose 4. This dose is necessary only for children ages 12-59 months regardless of risk, or age 60-71 months with any risk who received three doses before age 12 months.

A parent-friendly vaccine schedule for children and adolescents is available on the CDC’s website.

“Vaccines are essential for the health of our whole society, including children and adolescents,” Dr. O’Leary said in a press release from AAP. “These schedules provide a road map [that] parents and pediatricians can follow to help children get the vaccines they need so their immune systems will be ready to recognize and resist diseases.”

As previously, the 2023 schedule was adjusted to ensure consistency between the formats of the childhood/adolescent and adult immunization guidance. A meeting of stakeholder organizations in October 2022 harmonized the two formats.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2023.

In a policy statement published online in the journal Pediatrics, the AAP said the updated recommendations do not include major changes from those released in 2022 by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

In one small shift, COVID-19 is now addressed in the main text instead of being relegated to the notes section.

“And a new vaccine – Priorix [GlaxoSmithKline] – has been added for MMR [measles, mumps, rubella], so now there are two available,” Sean T. O’Leary, MD, MPH, chair of the AAP’s Committee on Infectious Diseases, told this news organization. “There’s also a second pneumococcal conjugate vaccine listed, PCV15, and this and PCV13 can essentially be used interchangeably.”

Minor updates to the schedule, reflected on the cover page, relate to vaccines for COVID-19, dengue fever, and pneumococcal disease, added Dr. O’Leary, a professor of pediatrics at the University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora.

The committee also changed layouts to improve the usability of the schedule. Updated annually, the guidance provides a table on recommended pediatric immunizations from birth to age 18 years, and catch-up recommendations for children aged 4 months to 18 years who start their vaccinations late or are more than 1 month behind the recommended age for vaccine administration.

“We hope this annual update will encourage clinicians to make sure all their patients are up to date on their routine vaccinations,” Dr. O’Leary said. “It’s an opportunity to develop strategies to improve vaccination rates.”

The 2023 schedule follows news from the CDC that kindergarten vaccination rates declined during the 2021-2022 school year. Only 93% of kindergarteners obtained full vaccinations, representing a drop of 1 percentage point from the year before and 2 percentage points from the 2019-2020 school year.

The dip in coverage has been attributed to disruptions caused by the COVID-19 pandemic. AAP advises health care professionals to urge families to make sure their child’s vaccines are current.

Among other additions:
 

In Table 1

• MMR: Second vaccine added (Priorix, GlaxoSmithKline Biologicals)
• Pneumococcal disease: second conjugate vaccine, PCV15, added (Vaxneuvance, Merck Sharp & Dohme).
• COVID-19: New row added.
• Dengue: Text changed from “Seropositive in endemic areas only” to “Seropositive in endemic dengue areas.”
• Inactivated polio vaccine: “See Notes” added to the column for children aged 18 years.

In Table 2

• PCV: Dose 3 to dose 4 interval revised to align with ACIP’s recommendation for dose 4. This dose is necessary only for children ages 12-59 months regardless of risk, or age 60-71 months with any risk who received three doses before age 12 months.

A parent-friendly vaccine schedule for children and adolescents is available on the CDC’s website.

“Vaccines are essential for the health of our whole society, including children and adolescents,” Dr. O’Leary said in a press release from AAP. “These schedules provide a road map [that] parents and pediatricians can follow to help children get the vaccines they need so their immune systems will be ready to recognize and resist diseases.”

As previously, the 2023 schedule was adjusted to ensure consistency between the formats of the childhood/adolescent and adult immunization guidance. A meeting of stakeholder organizations in October 2022 harmonized the two formats.

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

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

The Society for Cardiovascular Angiography and Interventions has issued an updated expert consensus statement to provide clearer guidance on what percutaneous coronary angioplasty cases can be done in outpatient settings such as ambulatory surgery centers (ASCs) and office-based laboratories and which are best left to more traditional settings, such as hospitals with full cardiac support.

PCI has evolved quickly since SCAI issued its last update almost 9 years ago. The updated statement, published online in the Journal of the Society for Cardiovascular Angiography and Interventions, notes that the proportion of same-day PCI discharges has increased from 4.5% in 2009 to 28.6% in 2017.

The statement also notes that the Medicare facility fee for outpatient PCI in an ASC is about 40% less than the hospital fee: $6,111 versus $10,258 for the facility fee for 2022. The Centers for Medicare & Medicaid Services in 2020 extended coverage for PCIs in ASCs.
 

Rationale for update

Writing group chair Cindy Grines, MD, explained the rationale for updating the statement now. “The 2014 SCAI statement was very conservative, recommending only the simplest of cases be done without surgical backup,” Dr. Grines, chief scientific officer at Northside Hospital Cardiovascular Institute in Atlanta, said in an interview.

The statement drew on 12 global studies from 2015 to 2022 that evaluated more than 8 million PCIs at facilities with and without surgery on site. Dr. Grines noted those studies reported complication rates as low as 0.1% in PCI procedures in centers without surgical backup.

She also noted that the writing committee also received input that “by restricting the use of certain devices such as atherectomy, some patients who needed it as a bailout could be harmed.”

Another factor in prompting the statement update, Dr. Grines said: “Many hospitals have consolidated into heath systems, and these systems consolidated bypass surgery into one center. Therefore, centers with high volume, experienced operators, and excellent outcomes were now left with no surgery on site. It didn’t make sense to withdraw complex PCI from these centers who haven’t sent a patient for emergency bypass in several years.”
 

Statement guidance

The centerpiece of the update is an algorithm that covers the range of settings for PCI, from having a surgeon on site to ACS or office-based lab.

For example, indications for on-site surgical capability are PCI of the last remaining patent vessel or retrograde approach to epicardial chronic total occlusion (CTO), and when the patient is a candidate for surgery.

Indications for PCI in a hospital without on-site surgery but with percutaneous ventricular assist device or extracorporeal membrane oxygenation, calcium modification devices and high PCI volume are patients with decreased left ventricular ejection fraction, unprotected left main artery, CTO, or degenerated vein grafts.

For patients at high risk for transfusion, acute kidney injury or vascular complications, or who have high baseline respiratory risk, a hospital without on-site surgery but with respiratory care, blood bank, and vascular surgery services is indicated.

And for patients with none of the aforementioned characteristics or risks, ASC, office-based lab, or any hospital facility is acceptable.

The statement also provides guidance for operator experience. Those with less than 3 years’ experience, considered to have limited exposure to atherectomy devices and limited ST-segmented elevation MI (STEMI)/shock experience, should avoid doing PCIs in an ASC and performing atherectomy cases on their own, and have a colleague review case selection and assist in higher-risk cases. Experienced (3-10 years’ experience) and very experienced (more than 10 years’) should be able to perform in any setting and be competent with, if not highly experienced with, atherectomy and STEMI/shock.

Dr. Grines acknowledged the writing group didn’t want to set a specific operator volume requirement. “However, we recognize that lifetime operator experience is particularly important in more complex cases such as CTO, atherectomy, bifurcation stenoses, etc.,” she said. “In addition, performing these cases at a larger institution that has other operators that may assist in the event of a complication is very important. Specifically, we did not believe that recent fellow graduates with less than 3 years in practice or low-volume operators should attempt higher-risk cases in a no-SOS [surgeon-on-site] setting or perform cases in ASC or office-based labs where no colleagues are there to assist in case of a complication.”

In an interview, Gregory J. Dehmer, MD, professor of medicine at Virginia Tech University, Roanoke, reprised the theme of his accompanying editorial. “Things are evolving again, as Bob Dylan would say, ‘The Times They Are A-Changin’, so it’s very timely that the society in collaboration with other professional societies updated what are guidelines and rules of road if you’re going to do PCI in ASCs or office based laboratories,” said Dr. Dehmer, who chaired the writing committees of the 2007 and 2014 SCAI expert statements on PCI.

Having this statement is important for centers that don’t have on-site surgical backup, he said. “You couldn’t sustain a PCI operation at a rural hospital on just acute MIs alone. The key thing is that all of this built upon numerous studies both in the U.S. and abroad that showed the safety of doing elective cases – not only STEMIs, but elective PCI – at facilities without on-site surgery.”

CMS pushed the envelope when it decided to reimburse PCIs done in ASCs, Dr. Dehmer said. “That was not based on a lot of data. It was kind of a leap of faith. It’s logical that this should work, but in order for it to work and be safe for pats you have to follow the rules. That’s where SCAI stepped in at this point and said this is a whole new environment and we need to set some ground rules for physicians of who and who should not be having these procures in an office-based lab or an ambulatory surgery center.”

Dr. Grines and Dr. Dehmer have no relevant disclosures.
 

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

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

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

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

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

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

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

Attention-deficit/hyperactivity disorder (ADHD) is often a very challenging condition for parents to manage, both because of the “gleeful mayhem” children with ADHD manifest and because of the nature of effective treatments. Multiple randomized controlled studies and meta-analyses have demonstrated that stimulant medication with behavioral interventions is the optimal first-line treatment for children with both subtypes of ADHD, and that medications alone are superior to behavioral interventions alone. By improving attention and impulse control, the medications effectively decrease the many negative interactions with teachers, peers, and parents, aiding development and healthy self-esteem.

But many parents feel anxious about treating their young children with stimulants. Importantly, how children with ADHD will fare as adults is not predicted by their symptom level, but instead by the quality of their relationships with their parents, their ability to perform at school, and their social skills. Bring this framework to parents as you listen to their questions and help them decide on the best approach for their family. To assist you in these conversations, we will review the evidence for (or against) several of the most common alternatives to medication that parents are likely to ask about.
 

Diets and supplements

Dietary modifications are among the most popular “natural” approaches to managing ADHD in children. Diets that eliminate processed sugars or food additives (particularly artificial food coloring) are among the most common approaches discussed in the lay press. These diets are usually very time-consuming and disruptive for families to follow, and there is no evidence to support their general use in ADHD management. Those studies that rigorously examined them suggest that, for children with severe impairment who have failed to respond to medications for ADHD, a workup for food intolerance or nutritional deficits may reveal a different problem underlying their behavioral difficulties.¹

Similarly, supplementation with high-dose omega-3 fatty acids is modestly helpful only in a subset of children with ADHD symptoms, and not nearly as effective as medications or behavioral interventions. Spending time on an exacting diet or buying expensive supplements is very unlikely to relieve the children’s symptoms and may only add to their stress at home. The “sugar high” parents note may be the rare joy of eating a candy bar and not sugar causing ADHD. Offer parents the guidance to focus on a healthy diet, high in fruits and vegetables, whole grains, and healthy protein, and on meals that emphasize family time instead of struggles around food.
 

Neurofeedback

Neurofeedback is an approach that grew out of the observation that many adults with ADHD had resting patterns of brain wave activity different from those of neurotypical adults. In neurofeedback, patients learn strategies that amplify the brain waves associated with focused mental activity, rather than listless or hyperactive states. Businesses market this service for all sorts of illnesses and challenges, ADHD chief among them. Despite the marketing, there are very few randomized controlled studies of this intervention for ADHD in youth, and those have shown only the possibility of a benefit.

While there is no evidence of serious side effects, these treatments are time-consuming and expensive and unlikely to be covered by any insurance. You might suggest to parents that they could achieve some of the same theoretical benefits by looking for hobbies that invite sustained focus in their children. That is, they should think about activities that interest the children, such as music lessons or karate, that they could practice in classes and at home. If the children find these activities even somewhat interesting (or just enjoy the reward of their parents’ or teachers’ attention), regular practice will be supporting their developing attention while building social skills and authentic self-confidence, rather than the activities feeling like a treatment for an illness or condition.

Sleep and exercise

There are not many businesses or books selling worried and exhausted parents a quick nonmedication solution for their children’s ADHD in the form of healthy sleep and exercise habits. But these are safe and healthy ways to reduce symptoms and support development. Children with ADHD often enjoy and benefit from participating in a sport, and daily exercise can help with sleep and regulating their energy. They also often have difficulty with sleep initiation, and commonly do not get adequate or restful sleep. Inadequate sleep exacerbates inattention, distractibility, and irritability. Children with untreated ADHD also often spend a lot of time on screens, as it is difficult for them to shift away from rewarding activities, and parents can find screen time to be a welcome break from hyperactivity and negative interactions. But excessive screen time, especially close to bedtime, can worsen irritability and make sleep more difficult. Talk with parents about the value of establishing a routine around screen time, modest daily physical activity, and sleep that everyone can follow. If their family life is currently marked by late bedtimes and long hours in front of video games, this change will take effort. But within a few weeks, it could lead to significant improvements in energy, attention, and interactions at home.

Behavioral treatments

Effective behavioral treatments for ADHD do not change ADHD symptoms, but they do help children learn how to manage them. In “parent management training,” younger children and parents learn together how to avoid negative cycles of behavior (i.e., temper outbursts) by focusing on consistent routines and consequences that support children calmly learning to manage their impulses. The only other evidence-based treatment focuses on helping school age and older children develop executive functions – their planning, organization, and time management skills – with a range of age-appropriate tools. Both of these therapies may be more effective if the children are also receiving medication, but medication is not necessary for them to be helpful. It is important to note that play therapy and other evidence-based psychotherapies are not effective for management of ADHD, although they may treat comorbid problems.

Parent treatment

You may have diagnosed children with ADHD only to hear their parents respond by saying that they suspect (or know) that they (or their spouses) also have ADHD. This would not be surprising, as ADHD has one of the highest rates of heritability of psychiatric disorders, at 80%. Somewhere between 25% and 50% of parents of children with ADHD have ADHD themselves.² Screening for adults with ADHD, such as the Adult ADHD Self-Report Scale, is widely available and free. Speak with parents about the fact that behavioral treatments for their children’s ADHD are demanding. Such treatments require patience, calm, organization, and consistency.

If parents have ADHD, it may be very helpful for them to prioritize their own effective treatments, so that their attention and impulse control will support their parenting. They may be interested in learning about how treatment might also improve their performance at work and even the quality of their relationships. While there is some evidence that their children’s treatment outcome will hinge on the parents’ treatment,³ they deserve good care independent of the expectations of parenting.

Families benefit from a comprehensive “ADHD plan” for their children. This would start with an assessment of the severity of their children’s symptoms, specifying their impairment at home, school, and in social relationships. It would include their nonacademic performance, exploration of interests, and developing self-confidence. All of these considerations lead to setting reasonable expectations so the children can feel successful. Parents should think about how best to structure their children’s schedules to promote healthy sleep, exercise, and nutrition, and to expand opportunities for building their frustration tolerance, social skills, and executive function.

Parents will need to consider what kind of supports they themselves need to offer this structure. There are good resources available online for information and support, including Children and Adults with ADHD (chadd.org) and the ADHD Resource Center from the American Academy of Child and Adolescent Psychiatry (aacap.org). This approach may help parents to evaluate the potential risks and benefits of medications as a component of treatment. Most of the quick fixes for childhood ADHD on the market will take a family’s time and money without providing meaningful improvement. Parents should focus instead on the tried-and-true routines and supports that will help them to create the setting at home that will enable their children to flourish.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Millichap JG and Yee MM. Pediatrics. 2012 Feb;129(2):330-7.

2. Grimm O et al. Curr Psychiatry Rep. 2020 Feb 27;22(4):18.

3. Chronis-Tuscano A et al. J Abnorm Child Psychol. 2017 Apr;45(3):501-7.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.

“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”

The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.

As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.

Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”

Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”

Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?

Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.

• The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
• The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
• The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.

What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.

“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”

That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.

And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”

The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”

Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.

The study has no external funding. The authors report no disclosures.

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.