The FDA defines “off-label” prescribing as prescribing an FDA-approved medication for an unapproved use, such as for an unapproved clinical indication, for a higher-than-approved dose, or for a patient who is not part of the FDA-approved population (eg, children or geriatric patients).¹ Off-label prescribing is common in psychiatry; approximately 13% of psychiatry patients are prescribed off-label psychotropic medications.² The American Psychiatric Association strongly supports “the autonomous clinical decision-making authority of a physician” and “a physician’s lawful use of an FDA-approved drug product or medical device for an off-label indication when such use is based upon sound scientific evidence in conjunction with sound medical judgment.”³ Because many psychiatric diagnoses have no FDA-approved medications, off-label prescribing often may be a psychiatrist’s only pharmacologic option.

Unfortunately, off-label prescribing can increase a psychiatrist’s risk for liability when treatment falls short of patients’ expectations, or when patients allege that they were injured by the use of an off-label medication. Off-label prescribing does not automatically lead to losing a malpractice suit because the FDA states that physicians can prescribe approved medications for any scientifically supported use, including off-label.¹ Medical malpractice lawsuits alleging negligence in prescribing practices, such as off-label prescribing, typically include allegations against the psychiatrist for failure to⁴:

• adequately assess the patient
• consult the patient’s medical records
• obtain informed consent from the patient
• appropriately prescribe a medication for the clinical indication, dosage, patient’s age, etc.
• monitor for adverse effects and therapeutic effectiveness.

Steps to minimize your risk

When prescribing a medication off-label, the following approaches can help reduce your liability risk:

Conduct a comprehensive clinical assess­ment. This should include requesting and reviewing your patient’s medical records.

Explain your motivation. Explain to your patient how prescribing an off-label medication can directly benefit him/her. Make it clear that you are not conducting experimental research by prescribing off-label because some patients might perceive this as a covert form of research.

Know the medications you prescribe. Although this sounds obvious, psychiatrists should thoroughly understand how each medication they prescribe is likely to clinically affect their patient. This information is available from many sources, including the FDA’s medication information sheets and the manufacturer’s medication package inserts. If possible, make sure that your off-label prescribing is supported by reputable, peer-reviewed literature.

Obtain informed consent. Tell your patient that the medication you are recommending is being prescribed off-label. Discuss the medication’s risks, benefits, adverse effects, associated “black-box” warnings, off-label uses, and alternatives to the off-label medication.⁴ Allow time for the patient to ask questions about these treatments.

Continue to: Document all steps

Document all steps. There is an adage in medicine that “If it’s not written, it wasn’t done.” To help reduce your liability risk when prescribing off-label, be sure to document the following⁴:

• your clinical assessment
• information you gleaned from the patient’s medical records
• your review of information regarding both therapeutic and adverse effects of the medication you want to prescribe
• your discussion of informed consent, including documentation that the patient is aware that the medication is being prescribed off-label
• your clinical rationale for why the off-label medication is in the patient’s best interest.

Also, document the steps you take to monitor for adverse events and therapeutic effectiveness.⁴ Overall, the goal of documentation should be to support the adequate continuing care of our patients.

The FDA defines “off-label” prescribing as prescribing an FDA-approved medication for an unapproved use, such as for an unapproved clinical indication, for a higher-than-approved dose, or for a patient who is not part of the FDA-approved population (eg, children or geriatric patients).¹ Off-label prescribing is common in psychiatry; approximately 13% of psychiatry patients are prescribed off-label psychotropic medications.² The American Psychiatric Association strongly supports “the autonomous clinical decision-making authority of a physician” and “a physician’s lawful use of an FDA-approved drug product or medical device for an off-label indication when such use is based upon sound scientific evidence in conjunction with sound medical judgment.”³ Because many psychiatric diagnoses have no FDA-approved medications, off-label prescribing often may be a psychiatrist’s only pharmacologic option.

Unfortunately, off-label prescribing can increase a psychiatrist’s risk for liability when treatment falls short of patients’ expectations, or when patients allege that they were injured by the use of an off-label medication. Off-label prescribing does not automatically lead to losing a malpractice suit because the FDA states that physicians can prescribe approved medications for any scientifically supported use, including off-label.¹ Medical malpractice lawsuits alleging negligence in prescribing practices, such as off-label prescribing, typically include allegations against the psychiatrist for failure to⁴:

• adequately assess the patient
• consult the patient’s medical records
• obtain informed consent from the patient
• appropriately prescribe a medication for the clinical indication, dosage, patient’s age, etc.
• monitor for adverse effects and therapeutic effectiveness.

Steps to minimize your risk

When prescribing a medication off-label, the following approaches can help reduce your liability risk:

Conduct a comprehensive clinical assess­ment. This should include requesting and reviewing your patient’s medical records.

Explain your motivation. Explain to your patient how prescribing an off-label medication can directly benefit him/her. Make it clear that you are not conducting experimental research by prescribing off-label because some patients might perceive this as a covert form of research.

Know the medications you prescribe. Although this sounds obvious, psychiatrists should thoroughly understand how each medication they prescribe is likely to clinically affect their patient. This information is available from many sources, including the FDA’s medication information sheets and the manufacturer’s medication package inserts. If possible, make sure that your off-label prescribing is supported by reputable, peer-reviewed literature.

Obtain informed consent. Tell your patient that the medication you are recommending is being prescribed off-label. Discuss the medication’s risks, benefits, adverse effects, associated “black-box” warnings, off-label uses, and alternatives to the off-label medication.⁴ Allow time for the patient to ask questions about these treatments.

Continue to: Document all steps

Document all steps. There is an adage in medicine that “If it’s not written, it wasn’t done.” To help reduce your liability risk when prescribing off-label, be sure to document the following⁴:

• your clinical assessment
• information you gleaned from the patient’s medical records
• your review of information regarding both therapeutic and adverse effects of the medication you want to prescribe
• your discussion of informed consent, including documentation that the patient is aware that the medication is being prescribed off-label
• your clinical rationale for why the off-label medication is in the patient’s best interest.

Also, document the steps you take to monitor for adverse events and therapeutic effectiveness.⁴ Overall, the goal of documentation should be to support the adequate continuing care of our patients.

The FDA defines “off-label” prescribing as prescribing an FDA-approved medication for an unapproved use, such as for an unapproved clinical indication, for a higher-than-approved dose, or for a patient who is not part of the FDA-approved population (eg, children or geriatric patients).¹ Off-label prescribing is common in psychiatry; approximately 13% of psychiatry patients are prescribed off-label psychotropic medications.² The American Psychiatric Association strongly supports “the autonomous clinical decision-making authority of a physician” and “a physician’s lawful use of an FDA-approved drug product or medical device for an off-label indication when such use is based upon sound scientific evidence in conjunction with sound medical judgment.”³ Because many psychiatric diagnoses have no FDA-approved medications, off-label prescribing often may be a psychiatrist’s only pharmacologic option.

Unfortunately, off-label prescribing can increase a psychiatrist’s risk for liability when treatment falls short of patients’ expectations, or when patients allege that they were injured by the use of an off-label medication. Off-label prescribing does not automatically lead to losing a malpractice suit because the FDA states that physicians can prescribe approved medications for any scientifically supported use, including off-label.¹ Medical malpractice lawsuits alleging negligence in prescribing practices, such as off-label prescribing, typically include allegations against the psychiatrist for failure to⁴:

• adequately assess the patient
• consult the patient’s medical records
• obtain informed consent from the patient
• appropriately prescribe a medication for the clinical indication, dosage, patient’s age, etc.
• monitor for adverse effects and therapeutic effectiveness.

Steps to minimize your risk

When prescribing a medication off-label, the following approaches can help reduce your liability risk:

Conduct a comprehensive clinical assess­ment. This should include requesting and reviewing your patient’s medical records.

Explain your motivation. Explain to your patient how prescribing an off-label medication can directly benefit him/her. Make it clear that you are not conducting experimental research by prescribing off-label because some patients might perceive this as a covert form of research.

Know the medications you prescribe. Although this sounds obvious, psychiatrists should thoroughly understand how each medication they prescribe is likely to clinically affect their patient. This information is available from many sources, including the FDA’s medication information sheets and the manufacturer’s medication package inserts. If possible, make sure that your off-label prescribing is supported by reputable, peer-reviewed literature.

Obtain informed consent. Tell your patient that the medication you are recommending is being prescribed off-label. Discuss the medication’s risks, benefits, adverse effects, associated “black-box” warnings, off-label uses, and alternatives to the off-label medication.⁴ Allow time for the patient to ask questions about these treatments.

Continue to: Document all steps

Document all steps. There is an adage in medicine that “If it’s not written, it wasn’t done.” To help reduce your liability risk when prescribing off-label, be sure to document the following⁴:

• your clinical assessment
• information you gleaned from the patient’s medical records
• your review of information regarding both therapeutic and adverse effects of the medication you want to prescribe
• your discussion of informed consent, including documentation that the patient is aware that the medication is being prescribed off-label
• your clinical rationale for why the off-label medication is in the patient’s best interest.

Also, document the steps you take to monitor for adverse events and therapeutic effectiveness.⁴ Overall, the goal of documentation should be to support the adequate continuing care of our patients.

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

Psychiatric emergencies—such as a patient who is agitated, self-destructive, or suicidal—may arise in a variety of settings, including emergency departments and inpatient units.¹ Before emergently prescribing psychotropic medications to address acute psychiatric symptoms, there are numerous factors a clinician needs to consider.^1-3 Asking the following questions may help you quickly obtain important clinical information to determine which medication to use during a psychiatric emergency:

Age. Is the patient a child, adolescent, adult, or older adult?

Allergies. Does the patient have any medication allergies or sensitivities?

Behaviors. What are the imminent dangerous behaviors that warrant emergent medication use

Collateral information. If the patient was brought by police or family, how was he/she behaving in the community or at home? If brought from a correctional facility or other institution, how did he/she behave in that setting?

Concurrent diagnoses/interventions. Does the patient have a psychiatric or medical diagnosis? Is the patient receiving any pharmacologic or nonpharmacologic treatments?

First visit. Is this the patient’s first visit to your facility? Or has the patient been to the facility previously and/or repeatedly? Has the patient ever been prescribed psychotropic medications? If the patient has received emergent medications before, which medications were used, and were they helpful?

Continue to: Legal status

Legal status. Is the patient voluntary for treatment or involuntary for treatment? If voluntary, is involuntary treatment needed?

Street. Was this patient evaluated in a medical setting before presenting to your facility? Or did this patient arrive directly from the community/street?

Substance use. Has the patient been using any licit and/or illicit substances?

In my experience with psychiatric emergencies, asking these questions has helped guide my decision-making during these situations. They have helped me to determine the appropriate medication, route of administration, dose, and monitoring requirements. Although other factors can impact clinicians’ decision-making in these situations, I have found these questions to be a good starting point.

References

1. CDC. Coronavirus Disease 2019 (COVID-19): Cases in the US. www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed August 18, 2020.
2. US Department of Health and Human Services. Fact Sheet: explaining Operation Warp Speed. www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html. Accessed August 18, 2020.
3. O’Callahan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 vaccine at warp speed. JAMA. 2020;324:437-438.
4. Pardi N, Hogan MJ, Porter FW, et al. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261-279.
5. Lurie N, Sharfstein JM, Goodman JL. The development of COVID-19 vaccines: safeguards needed [commentary]. JAMA. 2020;324:439-440.
6. Salman DA, Akhtar A, Mergler MJ, et al; H1N1 Working Group of Federal Immunization Safety Task Force. Immunization safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program. Pediatrics. 2011;127(suppl 1):S78-S86.

References

1. CDC. Coronavirus Disease 2019 (COVID-19): Cases in the US. www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed August 18, 2020.
2. US Department of Health and Human Services. Fact Sheet: explaining Operation Warp Speed. www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html. Accessed August 18, 2020.
3. O’Callahan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 vaccine at warp speed. JAMA. 2020;324:437-438.
4. Pardi N, Hogan MJ, Porter FW, et al. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261-279.
5. Lurie N, Sharfstein JM, Goodman JL. The development of COVID-19 vaccines: safeguards needed [commentary]. JAMA. 2020;324:439-440.
6. Salman DA, Akhtar A, Mergler MJ, et al; H1N1 Working Group of Federal Immunization Safety Task Force. Immunization safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program. Pediatrics. 2011;127(suppl 1):S78-S86.

References

1. CDC. Coronavirus Disease 2019 (COVID-19): Cases in the US. www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed August 18, 2020.
2. US Department of Health and Human Services. Fact Sheet: explaining Operation Warp Speed. www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html. Accessed August 18, 2020.
3. O’Callahan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 vaccine at warp speed. JAMA. 2020;324:437-438.
4. Pardi N, Hogan MJ, Porter FW, et al. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261-279.
5. Lurie N, Sharfstein JM, Goodman JL. The development of COVID-19 vaccines: safeguards needed [commentary]. JAMA. 2020;324:439-440.
6. Salman DA, Akhtar A, Mergler MJ, et al; H1N1 Working Group of Federal Immunization Safety Task Force. Immunization safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program. Pediatrics. 2011;127(suppl 1):S78-S86.

It has been a busy month. September will mark the ninth month of U.S. COVID-19 with the country now surpassing 5 million cases and more than 175,000 deaths. Daily life and our medical practices will never be the same. Many have lost friends, family, businesses, and hope. Instead of acting as a nation to pull through this together, we seem to be entering a continual state of Thoreau solitude combined with Garrett Hardin’s tragedy of the commons.

In the last 2 months GI & Hepatology News published a two-part opinion piece about the acquisition of physicians’ GI practices by private equity (PE) companies. I received a strongly worded (but justified) email criticizing the newspaper for being one sided and not declaring a conflict of interest on the part of the author. For both issues, I take sole responsibility. While it is important for us to understand how PE is affecting GI practices, the author did have a personal stake in the success of this financial model. It is important to note that details of a PE acquisition can vary greatly depending on the PE company involved and PE companies looking to acquire practices now can be counted in the hundreds. The pros and cons of PE acquisitions were argued prior to COVID-19, but since the first quarter of 2020, the model is even more confusing. We will find out over the next several years whether this ever-proliferating model of practice financing will be successful or disastrous.

In November, GI & Hepatology News will publish a special supplement called Gastroenterology Data Trends. This publication will include brief, but robust snapshots of major trends in topics ranging from NAFLD, IBD, and GI cancers to the impact of COVID-19 on GI practices. We have collected a stellar group of authors to help us.

This month, the school year begins in ways that are still being sorted out. The “Big House” will not host its usual 110,000 fans packed like sardines watching Michigan football. I hope all of our readers skipped Sturgis this year. Stay safe, stay apart, and mask up.

John I. Allen, MD, MBA, AGAF
Editor in Chief

It has been a busy month. September will mark the ninth month of U.S. COVID-19 with the country now surpassing 5 million cases and more than 175,000 deaths. Daily life and our medical practices will never be the same. Many have lost friends, family, businesses, and hope. Instead of acting as a nation to pull through this together, we seem to be entering a continual state of Thoreau solitude combined with Garrett Hardin’s tragedy of the commons.

In the last 2 months GI & Hepatology News published a two-part opinion piece about the acquisition of physicians’ GI practices by private equity (PE) companies. I received a strongly worded (but justified) email criticizing the newspaper for being one sided and not declaring a conflict of interest on the part of the author. For both issues, I take sole responsibility. While it is important for us to understand how PE is affecting GI practices, the author did have a personal stake in the success of this financial model. It is important to note that details of a PE acquisition can vary greatly depending on the PE company involved and PE companies looking to acquire practices now can be counted in the hundreds. The pros and cons of PE acquisitions were argued prior to COVID-19, but since the first quarter of 2020, the model is even more confusing. We will find out over the next several years whether this ever-proliferating model of practice financing will be successful or disastrous.

In November, GI & Hepatology News will publish a special supplement called Gastroenterology Data Trends. This publication will include brief, but robust snapshots of major trends in topics ranging from NAFLD, IBD, and GI cancers to the impact of COVID-19 on GI practices. We have collected a stellar group of authors to help us.

This month, the school year begins in ways that are still being sorted out. The “Big House” will not host its usual 110,000 fans packed like sardines watching Michigan football. I hope all of our readers skipped Sturgis this year. Stay safe, stay apart, and mask up.

John I. Allen, MD, MBA, AGAF
Editor in Chief

It has been a busy month. September will mark the ninth month of U.S. COVID-19 with the country now surpassing 5 million cases and more than 175,000 deaths. Daily life and our medical practices will never be the same. Many have lost friends, family, businesses, and hope. Instead of acting as a nation to pull through this together, we seem to be entering a continual state of Thoreau solitude combined with Garrett Hardin’s tragedy of the commons.

In the last 2 months GI & Hepatology News published a two-part opinion piece about the acquisition of physicians’ GI practices by private equity (PE) companies. I received a strongly worded (but justified) email criticizing the newspaper for being one sided and not declaring a conflict of interest on the part of the author. For both issues, I take sole responsibility. While it is important for us to understand how PE is affecting GI practices, the author did have a personal stake in the success of this financial model. It is important to note that details of a PE acquisition can vary greatly depending on the PE company involved and PE companies looking to acquire practices now can be counted in the hundreds. The pros and cons of PE acquisitions were argued prior to COVID-19, but since the first quarter of 2020, the model is even more confusing. We will find out over the next several years whether this ever-proliferating model of practice financing will be successful or disastrous.

In November, GI & Hepatology News will publish a special supplement called Gastroenterology Data Trends. This publication will include brief, but robust snapshots of major trends in topics ranging from NAFLD, IBD, and GI cancers to the impact of COVID-19 on GI practices. We have collected a stellar group of authors to help us.

This month, the school year begins in ways that are still being sorted out. The “Big House” will not host its usual 110,000 fans packed like sardines watching Michigan football. I hope all of our readers skipped Sturgis this year. Stay safe, stay apart, and mask up.

John I. Allen, MD, MBA, AGAF
Editor in Chief

The first revision since 2015 to the European Society of Cardiology’s guidelines for diagnosing and managing non ST-elevation acute coronary syndrome placed increased reliance on high-sensitivity cardiac troponin testing for diagnosis, and embraced coronary CT to rule out lower-risk patients.

It also highlighted the need for personalized antiplatelet regimens, systems of care, and quality improvement.

The society released the new guidelines on August 29 (Eur Heart J. 2020 Aug 29;doi: 10.1093/eurheartj/ehaa575), and then devoted a session to them the next day at the virtual annual congress of the European Society of Cardiology to highlight some of the key updates, starting with the further emphasis placed on high-sensitivity cardiac troponin (hs-cTn), a reliance that contrasts with what remains inconsistent use of this metric in U.S. practice.

An hs-cTn test is the “preferred” diagnostic test and a “key” testing element, said Marco Roffi, MD, professor and director of interventional cardiology at University Hospital, Geneva, and a member of the guideline committee. He also stressed an update to the time frame of initial hs-cTn testing, which now involves a baseline reading and then a second measure after 2 hours to discern how the marker level is evolving with time. The guidelines advise against measuring any other biomarker of myocardial injury.
 

U.S. lags in measuring high-sensitivity cardiac troponin

U.S. medical systems and centers “are not uniform in adopting hs-cTn,” noted Richard J. Kovacs, MD, professor of cardiology at the Indiana University School of Medicine in Indianapolis. “The new European guidelines should spur U.S. institutions to at least take a close look at the advantages of hs-cTn. There is a strong case that it leads to more efficient emergency care and allows for quicker decisions and triage,” added Dr. Kovacs in an interview.

The new guideline’s emphasis on hs-cTn should hasten broader uptake in U.S. practice, agreed Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and a member of the guideline-writing panel

Another plus of the guidelines is its endorsement of an “organized approach to risk assessment” early on in these patients, said Dr. Kovacs, who is also the immediate past-president of the American College of Cardiology (ACC). An ACC committee is developing a new set of recommendations for managing patients with cardiac chest pain and is on track for release in 2021. It would represent the first update to U.S. guidelines for non ST-elevation ACS patients since 2014.

The new ESC guidelines give coronary CT angiography a class Ia rating as an alternative to invasive coronary angiography for assessing patients with a low or intermediate risk of having coronary disease, a “tremendous upgrade,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medical Heart Institute in Phoenix. While he welcomes this support for using coronary CT angiography in this setting, he acknowledged that the method remains limited in availability as it requires highly trained technicians to obtain good images and experienced clinicians to interpret the results.

Personalizing antiplatelet and antithrombotic treatments

Notable revisions to medical treatments to minimize ischemia included an admonition not to use routine pretreatment with a P2Y₁₂ receptor inhibitor (such as clopidogrel) before testing determines coronary anatomy.

Not using one of these antiplatelet drugs upfront on all patients “is a tremendous change,” Dr. Pershad said in an interview. Many patients currently get these drugs while awaiting an angiogram, but a more selected and deferred antiplatelet approach would be better when angiography shows that some patients need coronary bypass surgery, he noted. Recent study results have shown no added benefit from pretreatment, and its use can be especially problematic for patients who are slated for a planned invasive strategy, said Dr. Bhatt.

Dr. Pershad, Dr. Bhatt, and Dr. Kovacs all praised the overall emphasis on a personalized approach to treating patients with antiplatelet and antithrombotic drugs, with endorsement of a flexible approach to treatment intensity and duration. The guideline acknowledges the need to take into account a patient’s bleeding risk and comorbidities, and specifically endorsed the Academic Research Consortium’s formula for identifying and stratifying high bleeding risk (Eur Heart J. 2019 Aug 14;40[31]:2632-53).

The new guidelines also provide guidance on how to apply recent study results that addressed balancing efficacy and safety when pairing an antiplatelet drug with a direct-acting oral anticoagulant (DOAC) for patients who potentially need both drug classes, such as patients with atrial fibrillation and a recent ACS event. “It’s tremendous to get clarity on this issue; there’s been a lot of uncertainty,” said Dr. Pershad. The guidelines call for a week of triple therapy with a DOAC, aspirin, and a second antiplatelet drug, followed by 12 months on a DOAC plus a single antiplatelet drug, and then the DOAC alone as the “default” strategy for most patients, but also presents alternative options for patients with high risk for either bleeding or ischemia.

The new guidelines also give much-needed direction on how to apply an invasive strategy, with an emphasis on immediate intervention for within 2 hours for very-high-risk patients, and early intervention within 24 hours for high-risk patients. Adhering to this timetable can mean increasing catheter laboratory availability on an urgent basis over weekends, Dr. Bhatt noted.
 

Improving quality of care

A novel section in the new guidelines was devoted to nine quality measures that can help health systems and medical centers monitor their adherence to the guideline recommendations, track their performance relative to peer institutions, and follow changes in performance that result from quality improvement steps. It’s something of a “futuristic” step for a guideline to take, with a goal of persuading administrators to implement tracking of these measures and improve patient outcomes, noted Dr. Bhatt.

“It’s very important to see that this is not just a set of guidelines but also a tool to improve quality of care,” commented Dr. Kovacs. The key to success in this effort will be to follow registered patients, set benchmarks that systems can aspire to achieve, and use this to improve the quality of care.

Until now, optimizing care for patients with NSTE-ACS has been “challenging,” he said. “The focus must be on moving toward systems of care” that can provide consistent patient evaluation and care, and do it quickly, said Dr. Kovacs.

Dr. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, and Medtronic. Dr. Kovacs was formerly an employee of Eli Lilly. Dr. Bhatt has been a consultant to and has received research funding from several companies. Dr. Pershad had no disclosures.
 

mzoler@mdedge.com

The first revision since 2015 to the European Society of Cardiology’s guidelines for diagnosing and managing non ST-elevation acute coronary syndrome placed increased reliance on high-sensitivity cardiac troponin testing for diagnosis, and embraced coronary CT to rule out lower-risk patients.

It also highlighted the need for personalized antiplatelet regimens, systems of care, and quality improvement.

The society released the new guidelines on August 29 (Eur Heart J. 2020 Aug 29;doi: 10.1093/eurheartj/ehaa575), and then devoted a session to them the next day at the virtual annual congress of the European Society of Cardiology to highlight some of the key updates, starting with the further emphasis placed on high-sensitivity cardiac troponin (hs-cTn), a reliance that contrasts with what remains inconsistent use of this metric in U.S. practice.

An hs-cTn test is the “preferred” diagnostic test and a “key” testing element, said Marco Roffi, MD, professor and director of interventional cardiology at University Hospital, Geneva, and a member of the guideline committee. He also stressed an update to the time frame of initial hs-cTn testing, which now involves a baseline reading and then a second measure after 2 hours to discern how the marker level is evolving with time. The guidelines advise against measuring any other biomarker of myocardial injury.
 

U.S. lags in measuring high-sensitivity cardiac troponin

U.S. medical systems and centers “are not uniform in adopting hs-cTn,” noted Richard J. Kovacs, MD, professor of cardiology at the Indiana University School of Medicine in Indianapolis. “The new European guidelines should spur U.S. institutions to at least take a close look at the advantages of hs-cTn. There is a strong case that it leads to more efficient emergency care and allows for quicker decisions and triage,” added Dr. Kovacs in an interview.

The new guideline’s emphasis on hs-cTn should hasten broader uptake in U.S. practice, agreed Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and a member of the guideline-writing panel

Another plus of the guidelines is its endorsement of an “organized approach to risk assessment” early on in these patients, said Dr. Kovacs, who is also the immediate past-president of the American College of Cardiology (ACC). An ACC committee is developing a new set of recommendations for managing patients with cardiac chest pain and is on track for release in 2021. It would represent the first update to U.S. guidelines for non ST-elevation ACS patients since 2014.

The new ESC guidelines give coronary CT angiography a class Ia rating as an alternative to invasive coronary angiography for assessing patients with a low or intermediate risk of having coronary disease, a “tremendous upgrade,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medical Heart Institute in Phoenix. While he welcomes this support for using coronary CT angiography in this setting, he acknowledged that the method remains limited in availability as it requires highly trained technicians to obtain good images and experienced clinicians to interpret the results.

Personalizing antiplatelet and antithrombotic treatments

Notable revisions to medical treatments to minimize ischemia included an admonition not to use routine pretreatment with a P2Y₁₂ receptor inhibitor (such as clopidogrel) before testing determines coronary anatomy.

Not using one of these antiplatelet drugs upfront on all patients “is a tremendous change,” Dr. Pershad said in an interview. Many patients currently get these drugs while awaiting an angiogram, but a more selected and deferred antiplatelet approach would be better when angiography shows that some patients need coronary bypass surgery, he noted. Recent study results have shown no added benefit from pretreatment, and its use can be especially problematic for patients who are slated for a planned invasive strategy, said Dr. Bhatt.

Dr. Pershad, Dr. Bhatt, and Dr. Kovacs all praised the overall emphasis on a personalized approach to treating patients with antiplatelet and antithrombotic drugs, with endorsement of a flexible approach to treatment intensity and duration. The guideline acknowledges the need to take into account a patient’s bleeding risk and comorbidities, and specifically endorsed the Academic Research Consortium’s formula for identifying and stratifying high bleeding risk (Eur Heart J. 2019 Aug 14;40[31]:2632-53).

The new guidelines also provide guidance on how to apply recent study results that addressed balancing efficacy and safety when pairing an antiplatelet drug with a direct-acting oral anticoagulant (DOAC) for patients who potentially need both drug classes, such as patients with atrial fibrillation and a recent ACS event. “It’s tremendous to get clarity on this issue; there’s been a lot of uncertainty,” said Dr. Pershad. The guidelines call for a week of triple therapy with a DOAC, aspirin, and a second antiplatelet drug, followed by 12 months on a DOAC plus a single antiplatelet drug, and then the DOAC alone as the “default” strategy for most patients, but also presents alternative options for patients with high risk for either bleeding or ischemia.

The new guidelines also give much-needed direction on how to apply an invasive strategy, with an emphasis on immediate intervention for within 2 hours for very-high-risk patients, and early intervention within 24 hours for high-risk patients. Adhering to this timetable can mean increasing catheter laboratory availability on an urgent basis over weekends, Dr. Bhatt noted.
 

Improving quality of care

A novel section in the new guidelines was devoted to nine quality measures that can help health systems and medical centers monitor their adherence to the guideline recommendations, track their performance relative to peer institutions, and follow changes in performance that result from quality improvement steps. It’s something of a “futuristic” step for a guideline to take, with a goal of persuading administrators to implement tracking of these measures and improve patient outcomes, noted Dr. Bhatt.

“It’s very important to see that this is not just a set of guidelines but also a tool to improve quality of care,” commented Dr. Kovacs. The key to success in this effort will be to follow registered patients, set benchmarks that systems can aspire to achieve, and use this to improve the quality of care.

Until now, optimizing care for patients with NSTE-ACS has been “challenging,” he said. “The focus must be on moving toward systems of care” that can provide consistent patient evaluation and care, and do it quickly, said Dr. Kovacs.

Dr. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, and Medtronic. Dr. Kovacs was formerly an employee of Eli Lilly. Dr. Bhatt has been a consultant to and has received research funding from several companies. Dr. Pershad had no disclosures.
 

mzoler@mdedge.com

The first revision since 2015 to the European Society of Cardiology’s guidelines for diagnosing and managing non ST-elevation acute coronary syndrome placed increased reliance on high-sensitivity cardiac troponin testing for diagnosis, and embraced coronary CT to rule out lower-risk patients.

It also highlighted the need for personalized antiplatelet regimens, systems of care, and quality improvement.

The society released the new guidelines on August 29 (Eur Heart J. 2020 Aug 29;doi: 10.1093/eurheartj/ehaa575), and then devoted a session to them the next day at the virtual annual congress of the European Society of Cardiology to highlight some of the key updates, starting with the further emphasis placed on high-sensitivity cardiac troponin (hs-cTn), a reliance that contrasts with what remains inconsistent use of this metric in U.S. practice.

An hs-cTn test is the “preferred” diagnostic test and a “key” testing element, said Marco Roffi, MD, professor and director of interventional cardiology at University Hospital, Geneva, and a member of the guideline committee. He also stressed an update to the time frame of initial hs-cTn testing, which now involves a baseline reading and then a second measure after 2 hours to discern how the marker level is evolving with time. The guidelines advise against measuring any other biomarker of myocardial injury.
 

U.S. lags in measuring high-sensitivity cardiac troponin

U.S. medical systems and centers “are not uniform in adopting hs-cTn,” noted Richard J. Kovacs, MD, professor of cardiology at the Indiana University School of Medicine in Indianapolis. “The new European guidelines should spur U.S. institutions to at least take a close look at the advantages of hs-cTn. There is a strong case that it leads to more efficient emergency care and allows for quicker decisions and triage,” added Dr. Kovacs in an interview.

The new guideline’s emphasis on hs-cTn should hasten broader uptake in U.S. practice, agreed Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and a member of the guideline-writing panel

Another plus of the guidelines is its endorsement of an “organized approach to risk assessment” early on in these patients, said Dr. Kovacs, who is also the immediate past-president of the American College of Cardiology (ACC). An ACC committee is developing a new set of recommendations for managing patients with cardiac chest pain and is on track for release in 2021. It would represent the first update to U.S. guidelines for non ST-elevation ACS patients since 2014.

The new ESC guidelines give coronary CT angiography a class Ia rating as an alternative to invasive coronary angiography for assessing patients with a low or intermediate risk of having coronary disease, a “tremendous upgrade,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medical Heart Institute in Phoenix. While he welcomes this support for using coronary CT angiography in this setting, he acknowledged that the method remains limited in availability as it requires highly trained technicians to obtain good images and experienced clinicians to interpret the results.

Personalizing antiplatelet and antithrombotic treatments

Notable revisions to medical treatments to minimize ischemia included an admonition not to use routine pretreatment with a P2Y₁₂ receptor inhibitor (such as clopidogrel) before testing determines coronary anatomy.

Not using one of these antiplatelet drugs upfront on all patients “is a tremendous change,” Dr. Pershad said in an interview. Many patients currently get these drugs while awaiting an angiogram, but a more selected and deferred antiplatelet approach would be better when angiography shows that some patients need coronary bypass surgery, he noted. Recent study results have shown no added benefit from pretreatment, and its use can be especially problematic for patients who are slated for a planned invasive strategy, said Dr. Bhatt.

Dr. Pershad, Dr. Bhatt, and Dr. Kovacs all praised the overall emphasis on a personalized approach to treating patients with antiplatelet and antithrombotic drugs, with endorsement of a flexible approach to treatment intensity and duration. The guideline acknowledges the need to take into account a patient’s bleeding risk and comorbidities, and specifically endorsed the Academic Research Consortium’s formula for identifying and stratifying high bleeding risk (Eur Heart J. 2019 Aug 14;40[31]:2632-53).

The new guidelines also provide guidance on how to apply recent study results that addressed balancing efficacy and safety when pairing an antiplatelet drug with a direct-acting oral anticoagulant (DOAC) for patients who potentially need both drug classes, such as patients with atrial fibrillation and a recent ACS event. “It’s tremendous to get clarity on this issue; there’s been a lot of uncertainty,” said Dr. Pershad. The guidelines call for a week of triple therapy with a DOAC, aspirin, and a second antiplatelet drug, followed by 12 months on a DOAC plus a single antiplatelet drug, and then the DOAC alone as the “default” strategy for most patients, but also presents alternative options for patients with high risk for either bleeding or ischemia.

The new guidelines also give much-needed direction on how to apply an invasive strategy, with an emphasis on immediate intervention for within 2 hours for very-high-risk patients, and early intervention within 24 hours for high-risk patients. Adhering to this timetable can mean increasing catheter laboratory availability on an urgent basis over weekends, Dr. Bhatt noted.
 

Improving quality of care

A novel section in the new guidelines was devoted to nine quality measures that can help health systems and medical centers monitor their adherence to the guideline recommendations, track their performance relative to peer institutions, and follow changes in performance that result from quality improvement steps. It’s something of a “futuristic” step for a guideline to take, with a goal of persuading administrators to implement tracking of these measures and improve patient outcomes, noted Dr. Bhatt.

“It’s very important to see that this is not just a set of guidelines but also a tool to improve quality of care,” commented Dr. Kovacs. The key to success in this effort will be to follow registered patients, set benchmarks that systems can aspire to achieve, and use this to improve the quality of care.

Until now, optimizing care for patients with NSTE-ACS has been “challenging,” he said. “The focus must be on moving toward systems of care” that can provide consistent patient evaluation and care, and do it quickly, said Dr. Kovacs.

Dr. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, and Medtronic. Dr. Kovacs was formerly an employee of Eli Lilly. Dr. Bhatt has been a consultant to and has received research funding from several companies. Dr. Pershad had no disclosures.
 

mzoler@mdedge.com

The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.

On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.

Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.

The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.

The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.

The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.

Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.

The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.

There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.

Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.

“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.

In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.

“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.

Winners and losers

The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.

Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).

An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.

“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”

Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).

“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
 

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

The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.

On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.

Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.

The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.

The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.

The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.

Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.

The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.

There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.

Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.

“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.

In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.

“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.

Winners and losers

The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.

Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).

An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.

“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”

Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).

“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
 

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

The Trump administration is sticking with a plan to boost certain Medicare pay for many primary care and other specialties focused heavily on office visits while lowering that for other groups to balance these increased costs.

On Aug. 4, the Centers for Medicare & Medicaid Services posted on the Federal Register draft versions of two of its major annual payment measures: the physician fee schedule and the payment rule for hospital outpatient and ambulatory surgery center services. On Aug. 3, the CMS informally posted a copy of the physician fee schedule on its own website, allowing medical groups to begin reading the more than 1,300-page rule.

Federal officials normally use annual Medicare payment rules to make many revisions to policies as well as adjust reimbursement.

The draft 2021 physician fee schedule, for example, calls for broadening the authority of clinicians other than physicians to authorize testing of people enrolled in Medicare.

The CMS intends to allow nurse practitioners, physician assistants, and certain other health care professionals to more widely supervise diagnostic psychological and neuropsychological tests.

The draft 2021 hospital outpatient rule proposes a gradual changeover to allow more procedures to be performed on an outpatient basis. This shift could save money for Medicare as well as for the people enrolled in the giant federal health program who need these services, the CMS explained.

Medicare would begin with a change in status for almost 300 musculoskeletal-related services, making them eligible for payment in the hospital outpatient setting when appropriate, CMS wrote in a fact sheet.

The initial reaction to Medicare’s proposed 2021 rules centered on its planned redistribution of funds among medical specialties. The CMS had outlined this plan last year. It is part of longstanding efforts to boost pay for primary care specialists and other physicians whose practice centers more around office visits than procedures.

There is broad support in health policy circles for raising pay for these specialties, but there also are strong objections to the cuts the CMS plans to offset the cost of rising pay for some fields.

Susan R. Bailey, MD, president of the American Medical Association, addressed both of these ideas in an AMA news release on the proposed 2021 physician fee schedule. The increase in pay for office visits, covered under evaluation and management services (E/M), stems from recommendations on resource costs from the AMA/Specialty Society RVS Update Committee, Dr. Bailey said.

“Unfortunately, these office visit payment increases, and a multitude of other new CMS proposed payment increases, are required by statute to be offset by payment reductions to other services, through an unsustainable reduction of nearly 11% to the Medicare conversion factor,” Dr. Bailey explained.

In the news release, Dr. Bailey asked Congress to waive Medicare’s budget-neutrality requirements to allow increases without the cuts.

“Physicians are already experiencing substantial economic hardships due to COVID-19, so these pay cuts could not come at a worse time,” she said.

Winners and losers

The CMS details the possible winners and losers in its payment reshuffle in Table 90 of the proposed 2021 physician fee schedule. In the proposed rule, CMS notes in the draft that these figures are based upon estimates of aggregate allowed charges across all services furnished by physicians and other clinicians.

Specialties in line for increases under the 2021 draft rule include allergy/immunology (9%), endocrinology (17%), family practice (13%), geriatrics (4%), hematology/oncology (14%), internal medicine (4%), physician assistants (8%), psychiatry (8%), rheumatology (16%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–9%), emergency medicine (–6%), gastroenterology (–5%), general surgery (–7%), infectious disease (–4%), neurosurgery (–7%), physical/occupational therapy (–9%), plastic surgery (–7%), and radiology (–11%).

An umbrella group, the Surgical Care Coalition, had a quick statement ready about the CMS proposal. Writing on behalf of the group was David B. Hoyt, MD, executive director of the American College of Surgeons.

“Today’s proposed rule ignores both patients and the surgeons who care for them. The middle of a pandemic is no time for cuts to any form of health care, but today’s announcement moves ahead as if nothing has changed,” Dr. Hoyt said in the statement. “The Surgical Care Coalition believes no physician should see payment cuts that will reduce patients’ access to care.”

Making a similar request Aug. 4 in a unified statement were the American Physical Therapy Association (APTA), the American Occupational Therapy Association (AOTA), and the American Speech-Language-Hearing Association (ASHA).

“Our organizations call on Congress and CMS to advance well-reasoned fee schedule payment policies and waive budget neutrality,” the groups said.
 

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

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
• Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
• Preprocedure COVID testing (https://community.gastro.org/posts/22164)
• Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
• Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
• Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)

Roundtables (https://community.gastro.org/discussions/)

• Windows on Clinical GI
• Clinical Challenges in IBD: Ulcerative colitis and a fistula
• GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
• Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
• Preprocedure COVID testing (https://community.gastro.org/posts/22164)
• Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
• Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
• Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)

Roundtables (https://community.gastro.org/discussions/)

• Windows on Clinical GI
• Clinical Challenges in IBD: Ulcerative colitis and a fistula
• GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

• AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review (https://community.gastro.org/posts/22199)
• Establishing an acute colitis pathway (https://community.gastro.org/posts/22171)
• Preprocedure COVID testing (https://community.gastro.org/posts/22164)
• Patient case: Gastroesophageal varices (https://community.gastro.org/posts/22098)
• Patient case: IBD with intra-abdominal sepsis (https://community.gastro.org/posts/22055)
• Patient case: Hypervascular pancreatic parenchyma (https://community.gastro.org/posts/22039)

Roundtables (https://community.gastro.org/discussions/)

• Windows on Clinical GI
• Clinical Challenges in IBD: Ulcerative colitis and a fistula
• GI COVID-19 Connection: Implementing an effective long-term telehealth program in a post-COVID world

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration on Aug. 28 expanded its emergency use authorization (EUA) of remdesivir (Veklury) to include treatment of all adult and pediatric hospitalized COVID-19 patients, regardless of the severity of their disease.

An EUA of remdesivir issued in May allowed the drug to be used only for patients with severe COVID-19, specifically, COVID-19 patients with low blood oxygen levels or who need oxygen therapy or mechanical ventilation.

“Today, based on the Agency’s ongoing review of the EUA, including its review of the totality of scientific information now available, the FDA has determined that it is reasonable to believe Veklury may be effective for the treatment of suspected or laboratory-confirmed COVID-19 in all hospitalized adult and pediatric patients,” the FDA news release about the expanded EUA said. “The Agency’s review has also concluded that the known and potential benefits of Veklury outweigh the known and potential risks for these uses.”
 

‘Further evaluation’ needed

The EUA expansion is partially based on the results of a randomized, open-label trial that Gilead Sciences, remdesivir’s manufacturer, conducted at multiple sites.

The trial showed that a 5-day course of remdesivir was associated with statistically significant improvement among patients hospitalized with moderate COVID-19 in comparison with those receiving standard care. However, patients who were randomly assigned to a receive longer, 10-day remdesivir course had not improved significantly 11 days after treatment started, compared with those who received standard care.

Results with remdesivir in this trial and in two previously reported randomized trials varied, “raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped,” wrote Erin K. McCreary, PharmD, and Derek C. Angus, MD, MPH, with the University of Pittsburgh School of Medicine, in an editorial that accompanied publication of the trials in JAMA.

Angus previously expressed concern that expanding remdesivir’s EUA could “interrupt or thwart efforts to execute the needed RCTs [randomized controlled trials].

“We think there really needs to be further evaluation of remdesivir in large-scale RCTs adequately powered to understand in which patients, at which dose, given at which point in the course of illness leads to what concrete and tangible improvement in clinical outcomes,” he told Medscape Medical News.

“At this point, remdesivir definitely holds promise, but given the cost to produce and distribute the drug, it seems crucial to know with more certainty how best to use it,” Angus said.

The EUA expansion is also partially based on results from a randomized, double-blind, placebo-controlled clinical trial that the National Institutes of Allergy and Infectious Diseases conducted. In that trial, there was a statistically significant reduction in median recovery time and higher odds of clinical improvement after 2 weeks for hospitalized patients who received remdesivir.

For hospitalized patients with mild to moderate disease, the results were consistent with the overall study results but were not statistically significant.
 

This article first appeared on Medscape.com.

In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.

©Aunt_Spray/Thinkstock

It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.

The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.

Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.

“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”

Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.

“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”

Early evidence

Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. “Congenital Zika syndrome” refers specifically to the most severe effects from prenatal exposure: microcephaly, seizures, cerebral palsy, hearing and vision problems, feeding difficulties, and other disabilities. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.

Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.

“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.

“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”

Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.

The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.

As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.

Longer-term follow up

Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.

In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.

In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”

In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.

In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.

In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.

Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.

“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.

“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.

Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.

Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.

Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.

“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.

Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.” 

Exposed children need continued evaluation

Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said. 

When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.

The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.

Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.

Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.

“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
 

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

In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.

©Aunt_Spray/Thinkstock

It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.

The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.

Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.

“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”

Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.

“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”

Early evidence

Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. “Congenital Zika syndrome” refers specifically to the most severe effects from prenatal exposure: microcephaly, seizures, cerebral palsy, hearing and vision problems, feeding difficulties, and other disabilities. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.

Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.

“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.

“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”

Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.

The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.

As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.

Longer-term follow up

Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.

In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.

In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”

In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.

In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.

In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.

Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.

“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.

“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.

Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.

Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.

Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.

“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.

Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.” 

Exposed children need continued evaluation

Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said. 

When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.

The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.

Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.

Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.

“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
 

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

In 2020, “the virus” has come to mean one thing: SARS-CoV-2. But just a few years ago, Zika had the world's attention, as one news report after another described children with microcephaly born to women who'd been infected while pregnant.

©Aunt_Spray/Thinkstock

It can be difficult for physicians to determine whether a birth defect is the result of Zika. Most infections have few or no symptoms, and mothers may not know if they’ve been exposed. Karin Nielsen, MD, remembers one child in particular, a 9-month-old boy born with microcephaly whose parents brought the infant to her in 2018 because he had started having seizures.

The child was born in Mexico in 2017, when the Zika virus was still known to be circulating in the Americas, said Dr. Nielsen, a pediatric infectious disease specialist at the University of California, Los Angeles. Brain imaging revealed calcifications and other signs in the boy’s brain that were consistent with exposure. But his mother said she was never sick during pregnancy.

Because Zika is transmitted not just via mosquito and from mother to fetus but also sexually, Dr. Nielsen thinks the mother probably contracted an asymptomatic infection from her husband, who recalled having a rash when she was 4 months pregnant. When they participated in a research study, both parents tested positive for Zika antibodies.

“The child had the classic symptoms of congenital Zika syndrome,” Dr. Nielsen said. “He was 9 months old, he had microcephaly, and he was having mal seizures.”

Researchers have since learned that children with such classic symptoms represent only a small proportion of those affected by prenatal Zika exposure – about 3%-5%. The virus was at its height during the 2016-2016 epidemic and is not currently causing outbreaks. But as researchers have followed cohorts of children exposed to Zika in utero, they have found many subtler effects physicians will need to monitor as the children grow up.

“When we’re seeing hundreds of kids with microcephaly, we had a lot of people infected,” Dr. Nielsen said. “Microcephaly is only the tip of the iceberg.”

Early evidence

Microcephaly may be the most identifiable symptom of fetal Zika infection, but researchers tracking cohorts of exposed children have begun to build a more complete picture of what long-term effects might look like. “Congenital Zika syndrome” refers specifically to the most severe effects from prenatal exposure: microcephaly, seizures, cerebral palsy, hearing and vision problems, feeding difficulties, and other disabilities. But hundreds, if not thousands, of children have been exposed to Zika in the womb – it’s not clear how many, Dr. Nielsen said – and many show a range of effects that don’t officially qualify as congenital Zika syndrome.

Current estimates suggest about one third of exposed children have some type of neurologic or neurodevelopmental problem, even though prevalence of visible effects is much lower. Over time, the incidence of these effects has fluctuated; some developmental delays and sensory deficits began manifesting later in childhood whereas others, at least in a few children, have resolved.

“We’re just beginning to have some of the data that we need to think about the full spectrum of outcomes,” said Cindy Moore, MD, chief medical officer in the Division of Congenital and Developmental Disorders in the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.

“As we’re learning more and more, we’re learning the spectrum is expanding to less severe forms,” Dr. Moore said. “We do know that with some infections, there are later onset of problems.”

Studies published in 2018 described cohorts of children whose mothers had confirmed or suspected Zika infections during pregnancy in the French Territories of America (Guadalupe, Martinique, and French Guiana) and in Salvador, Brazil. The research provided valuable early data on the incidence of microcephaly and other severe effects in newborns, but noted the need for long-term follow up.

The U.S. Zika Pregnancy and Infant Registry is one of the largest such cohorts. In August 2018, researchers made their first report on data from the registry They looked at 1450 children age 1 or older who had undergone neuroimaging or screenings (developmental, vision, hearing) or both. In 6%, at least one birth defect was linked to Zika, and 9% had at least one neurodevelopmental abnormality.

As these children age past developmental milestones, more effects will likely manifest – even in those children whose appearance and imaging presented as healthy at birth.

Longer-term follow up

Nielsen at UCLA and M. Elisabeth Lopes Moreira, MD, of the Oswaldo Cruz Foundation in Rio de Janeiro, are following a cohort of more than 100 children born in Rio de Janeiro during Brazil’s 2015-2016 epidemic to mothers with symptomatic, PCR-confirmed Zika infections during pregnancy. In December 2018, their team reported that rates of severe neurodevelopmental delay and sensory dysfunction – 14% of 131 children aged 12-18 months – were higher than those found in earlier studies.

In August 2019, the team described neurodevelopmental, vision, and hearing outcomes in 216 Zika-exposed children 2 years after birth. They used the Bayley-III Scales of Infant and Toddler Development to assess cognitive, language and motor skills in 146 of the children. Forty percent of them were below or very below average in development, more than one third (35%) had language delays, 12% percent had hearing loss, and 7% had abnormal eye anatomy, such as underdeveloped retinas.

In two of the eight children in the cohort with microcephaly, the abnormality unexpectedly resolved. Although that finding received a lot of press, Dr. Nielsen pointed out that “not all microcephalies are created equal.”

In one case, a child born small for gestational age had proportional microcephaly: the baby›s head circumference met the criteria for microcephaly, but the infant›s head was proportional to the body so, as the child grew, the apparent microcephaly disappeared.

In the other case, the child was born with craniosynostosis, in which the skull sutures fuse too early – another effect seen with prenatal Zika exposure, Dr. Nielsen said. After corrective surgery, the child’s head circumference no longer met the definition of microcephaly, but the child still had symptoms related to congenital Zika: a developmental delay and calcifications in the brain. Meanwhile, two other children in the Rio cohort developed secondary microcephaly.

In another follow-up study of children up to age 4, Dr. Nielsen and colleagues found that both clinicians and family may think that Zika-exposed infants without microcephaly are developing normally, but that may not be true. Nearly 70% of children without microcephaly had neurologic abnormalities on physical examination, and more than half had failure to thrive because of poor feeding related to neurologic abnormalities.

Initially, some children may be able to mask subtle problems. A study published in January from Sarah B. Mulkey, MD, PhD, of Children’s National Hospital in Washington, DC, and colleagues described neurodevelopmental outcomes in 70 Colombian children up to 18 months old who had been exposed to Zika in utero. The children had a normal head circumference at birth and a normal fetal MRI, but – compared with typically developing peers – their communication, social cognition, and mobility scores on standardized assessments tended to decline as they got older.

“Especially in a very young child, there’s always going to be a possibility that you can compensate for a deficit, and it appears that at least some of these children are doing so,” said William J. Muller, MD, PhD, associate professor of pediatrics at Northwestern University, Chicago. When the children are older, certain behavioral effects will become easier to assess.

“With these children now approaching school age, understanding the full spectrum of neurodevelopmental abnormalities has important public health and educational system implications,” Dr. Muller and Dr. Mulkey wrote in a commentary about one of Dr. Nielsen’s studies.

Researchers face multiple barriers to understanding the long-term effects of fetal Zika infection. Many infants known to have been exposed in utero never received the recommended early assessments and haven’t been followed long-term. Particularly in Brazil, poverty, poor access to healthcare, and overcrowding all complicate surveillance efforts, Dr. Muller said. Stigma related to children’s neurodevelopmental problems also can potentially reduce a mother’s willingness to attend all follow-ups and assessments.

Some children may have been exposed but were never recognized as such, making it difficult for researchers to track their development and assemble a complete picture of prenatal Zika infection outcomes. Asymptomatic infection occurs in about 80% of Zika infections, though it’s not clear if that number holds for infections during pregnancy as well, according to Dr. Muller and Dr. Mulkey. Because nearly all the current research involves children whose mothers had symptomatic infections, the studies’ generalizability may be limited.

Those likely asymptomatic infections are also a major reason none of the cohorts have comparison groups.

“There are literally hundreds of things that can contribute to or cause developmental problems,” said Dr. Moore of the CDC, who noted that it would be nice to have a comparison group so as to know what Zika may not be responsible for. That said, it would be difficult-to-impossible to create a control group with similar geographic and demographic characteristics as the exposed children, a group who researchers can be certain weren’t exposed.

Neurodevelopmental disabilities occur in about 15% of the general population, making it difficult to determine whether Zika causes any or all long-term, less severe developmental findings in exposed children. The difficulty only compounds with time: the older a child is when a developmental problem is recognized, the harder it is to go back and say the problem is a result of something that occurred before birth, Dr. Moore said. “It’s a challenging field to say, this is what caused that outcome.” 

Exposed children need continued evaluation

Interpreting the clinical implications of available studies is also challenging. It can be difficult to distinguish between central nervous system damage and peripheral damage, leaving the true etiology of poor vision or hearing elusive. The Zika virus can attack both the optic nerve and the part of the brain that interprets what a person sees: “Are you not seeing well because that part of your brain is not developed, or is it just a problem with the eye?” Dr. Nielsen said. 

When problems can’t be precisely identified, successful interventions are harder. If the cochlea is normal, for instance, but the part of the brain that interprets sound or language has deficits, a hearing aid won’t help.

The services and interventions that children need depend on their specific developmental or cognitive deficits, regardless of the cause. But if clinicians know the cause is likely Zika exposure, they also know to look for other deficits.

Children showing likely effects of congenital Zika infection should be further evaluated for other possible birth defects and referred to a developmental specialist, early intervention services, and family support services. Depending on the child, primary care providers might consider referrals to an infectious disease specialist, clinical geneticist, neurologist, or other specialists.

Even with no confirmed infection or visible signs at birth, clinicians should remain vigilant with children who had possible exposure. A recently published study of 120 children conceived during the Zika outbreak in Paraíba, Brazil, assessed as infants and then again at 2 years old, exemplifies why. Researchers identified adverse neurologic outcomes and developmental delays in several children who had no physical evidence of birth defects as newborns, but whose antibody tests showed possible infection.

“In this post-epidemic period, with decreased Zika transmission and less public awareness,” wrote Dr. Mulkey and a colleague, “follow-up of these children is now more important than ever”.
 

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

An international panel of 49 melanoma specialists has come out against routine gene expression profile (GEP) testing for cutaneous melanoma, pending solid proof of clinical benefit.

“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.

Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.

The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.

The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.

Medicare reimburses at $7,193 per test for SLNB-eligible patients.

However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.

Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.

Company welcomes “further discussions”

“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.

Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”

“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”

Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
 

Cart before the horse

Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”

The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.

One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
 

First, do no harm

A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.

Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.

Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.

provided by MSKCC press office

“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.

“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.

“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.

Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.

Breast cancer standard of proof

Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.

With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.

On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.

“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.

But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.

What to do right now?

Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.

“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.

There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.

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

An international panel of 49 melanoma specialists has come out against routine gene expression profile (GEP) testing for cutaneous melanoma, pending solid proof of clinical benefit.

“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.

Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.

The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.

The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.

Medicare reimburses at $7,193 per test for SLNB-eligible patients.

However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.

Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.

Company welcomes “further discussions”

“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.

Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”

“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”

Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
 

Cart before the horse

Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”

The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.

One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
 

First, do no harm

A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.

Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.

Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.

provided by MSKCC press office

“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.

“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.

“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.

Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.

Breast cancer standard of proof

Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.

With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.

On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.

“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.

But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.

What to do right now?

Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.

“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.

There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.

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

An international panel of 49 melanoma specialists has come out against routine gene expression profile (GEP) testing for cutaneous melanoma, pending solid proof of clinical benefit.

“The currently published evidence is insufficient to establish that routine use of GEP testing provides additional clinical value for melanoma staging and prognostication beyond available clinicopathologic variables,” they argued.

Patients must be protected “from potentially inaccurate testing that may provide a false sense of security or perceived increased risk” that could lead to the wrong decisions, they said in a consensus statement from the United States’ national Melanoma Prevention Working Group. The statement was published on July 29 in JAMA Dermatology.

The GEP test for melanoma that is available in the United States – DecisionDx-Melanoma from Castle Biosciences – checks the expression levels of 31 genes reported to be associated with melanoma metastasis and recurrence. It uses quantitative reverse transcriptase and polymerase chain reaction on RNA from formalin-fixed, paraffin-embedded biopsy specimens.

The test stratifies patients as being at low, intermediate, or high risk. It is marketed as a guide to whether to perform sentinel lymph node biopsies (SLNB) on patients age 55 years or older with tumors less than 2 mm deep and to decide what levels of follow-up, imaging, and adjuvant treatment are appropriate for tumors at least 0.3 mm deep.

Medicare reimburses at $7,193 per test for SLNB-eligible patients.

However, this test is not endorsed by the American Academy of Dermatology or National Comprehensive Cancer Network outside of studies because the evidence of benefit is not strong enough, the consensus authors noted.

Even so, use of the test is growing, with up to 10% of cutaneous melanomas now being tested in the United States.

Company welcomes “further discussions”

“To date, thousands of clinicians – over 4,200 US clinicians in the last 12 months – have utilized our GEP test for cutaneous melanoma in their patients after reviewing our clinical data and determining that our test provides clinically actionable information that complements current melanoma staging,” said Castle Biosciences Vice President of Research and Development Bob Cook, PhD, when asked for comment.

Citing company-funded studies, he said that “the strength of the existing evidence in support of these claims has undergone rigorous evaluation to obtain Medicare reimbursement.”

“We believe that the application of the test to help guide [the] decision to pursue SLNB has the potential to realize significant cost savings by reducing unnecessary SLNB procedures, particularly in the T1 population.”

Asked for a reaction to the consensus statement, Dr. Cook said in an interview: “We recently launched two prospective studies with multiple centers nationwide that will involve thousands of patients and provide additional data relating our tests to patient outcomes. ... We welcome further discussions to promote collaborative efforts with centers that are part of the [Melanoma Prevention Working Group] to improve patient outcomes.”
 

Cart before the horse

Medicare, although it reimburses the test, has its doubts. Due to the “low strength of evidence,” the Centers for Medicare & Medicaid Services said in their local coverage determination that continued reimbursement depends on demonstration of 95% or greater distant-metastasis–free survival and melanoma-specific survival at 3 years “in patients directed to no SLNB by the test compared to standard of care, and ... evidence of higher SLNB positivity in patients selected for this procedure by the test compared to standard of care.”

The statement hints at the Achilles’ heel of GEP in melanoma – that is, the lack of evidence that test results improve outcomes. This was the main concern of the consensus statement; the cart is before the horse.

One of the consensus authors, David Polsky, MD, PhD, professor of dermatologic oncology at New York University, New York City, said that “most of the data for this test come from retrospectively collected patient groups.” The prospective studies have been generally small, with no comparator group. “While they have shown some promise in intermediate thickness melanoma, they have not yet demonstrated utility for thin, stage I melanomas.”
 

First, do no harm

A new meta-analysis of over 800 patients with cutaneous melanoma tested by DecisionDx-Melanoma, published in JAMA Dermatology alongside the consensus statement, shows how the tests perform.

Among patients with a recurrence, DecisionDx-Melanoma correctly classified 82% with stage II disease but only 29% with stage I disease as high risk. Among those without recurrence, the test correctly classified 90% of stage I patients but only 44% with stage II disease as low risk.

Similar results were seen with the melanoma GEP test available in Europe, MelaGenix (NeraCare GmbH). This test was developed from a panel that was narrowed to seven protective genes and one high-risk gene using a training cohort of 125 cutaneous melanomas.

provided by MSKCC press office

“The prognostic ability of GEP tests ... appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients,” commented the meta-analysis authors, led by Michael Marchetti, MD, an assistant professor of dermatology at Weill Cornell Medical College in New York City.

“Unknown are the harms associated with a false-positive result, which were 10-fold more frequent than true-positive results in patients with stage I disease,” they pointed out.

“Further research is needed to define the incremental improvement in risk predictions provided by the test beyond ... all other known clinicopathologic factors,” which include patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and other factors proven to be linked to outcomes, they said.

Studies so far suggesting benefit have incorporated a few of those factors, but not all of them. For now, “it is not clear which patients should be tested or how to act on the results,” Dr. Marchetti and colleagues concluded.

Breast cancer standard of proof

Larger, prospective studies are needed to address whether GEP testing can replace SLNB to predict relapse “and [can identify] patients who could be spared surveillance imaging and/or benefit from adjuvant therapy,” wrote the consensus authors. Follow-up also needs to be long enough to detect delayed recurrence of thin melanomas, they added.

With more research, there is reason to hope that gene expression profiling will help in melanoma; it’s already standard of care in breast cancer, they pointed out.

On the hope front, one cohort study evaluated whether DecisionDx-Melanoma could identify patients at low risk for positive lymph nodes in T1/T2 disease who were eligible for biopsy. Only 1.6% of subjects who were aged 65 years or older and identified by the test as low risk had a positive node.

“This is a promising direction of investigation ... in a narrow, defined population,” noted authors led by Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, in an opinion piece last spring.

But still, until there’s “clear evidence that [DecisionDx-Melanoma] results affect patient outcomes, we should not use it to influence care decisions in patients with thin” melanomas. Dermatology “should expect the same standards” of proof as breast cancer, they wrote.

What to do right now?

Despite the marketing, “think twice before ordering GEP tests for” T1a melanomas is the message in an editorial that accompanies the consensus statement. The 5- and 10-year melanoma-specific survival rates are 99% and 98%, respectively. GEP tests are unlikely to change these estimates significantly. In fact, the new meta-analysis indicates “that there may be an approximately 12% misassignment rate in this population,” wrote editorialists Warren Chan, of Baylor College of Medicine, Houston and Hensin Tsao, MD, PhD, director of the melanoma genetics program at Massachusetts General Hospital, Boston.

“Even if you use GEP testing and discover a low-risk class assignment for a 2 mm thick melanoma, avoid the urge to bypass the sentinel lymph node discussion. ... Nodal sampling, for good reasons, remains part of all major guidelines and determines eligibility for adjuvant treatments. ... Many of us engaged in genomics research believe that accurate [melanoma] GEP will be developed in time, but better tools and greater tenacity are needed,” they wrote.

There was no industry funding for the consensus statement and meta-analysis. Authors on the consensus statement reported numerous ties to pharmaceutical and other companies, as listed in the paper.

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