Journal of Clinical Outcomes Management

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

Psychedelics, including psilocybin and MDMA, are promising for a variety of psychiatric disorders, but there are few data showing how these drugs interact with traditional psychiatric medications, new research shows.

“Despite prolific psychedelic research and public interest, I was surprised to see little clinical research on how psilocybin and common psychiatric treatments interact,” study investigator Aryan Sarparast, MD, department of psychiatry, Oregon Health and Science University, Portland, told this news organization.

The review was published online March 7, 2022, in Psychopharmacology.
 

Need for RCTs

The Food and Drug Administration recently granted breakthrough therapy designation to psilocybin-assisted psychotherapy for major depression and treatment-resistant depression and to MDMA-assisted psychotherapy for PTSD.

The investigators assessed the volume of available research on interactions between psychedelics and traditional psychiatric medications, such as antidepressants.

They found 40 studies dating back to 1958, including 26 randomized controlled trials, 11 case reports, and 3 epidemiologic studies.

Only one randomized clinical trial evaluated the interaction between psilocybin and the most common psychiatric treatment, SSRIs, said Dr. Sarparast.

However, this study is “reassuring and overlaps with our hypothesis that there is a low risk of psilocybin and most psychiatric drugs causing harm when combined,” he noted.

Yet all of the clinical trials exclusively included young healthy adults, who were often recruited from university campuses. “We don’t have data on what happens when a depressed person on an SSRI takes psilocybin,” said Dr. Sarparast.

He added that he is concerned that the lack of evidence on drug-drug interactions will lead some providers to require patients to be tapered off existing traditional psychiatric medications before initiation of psilocybin therapy.

This may force vulnerable patients to choose between their existing therapy and psilocybin.

In addition, patients who opt for the “DIY method” of tapering risk mental health relapse and medication withdrawal effects. “That’s a very, very tough place to be,” Dr. Sarparast said.

Ideally, Dr. Sarparast would like to see a study in which depressed patients who have been receiving long-term antidepressant treatment are randomly assigned to received low, medium, and high doses of psilocybin. “This would clarify a lot of question marks.”
 

Evidence gap

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said: “The point in this article is very well taken. Indeed, more research is needed” on potential interactions between psychedelics and traditional psychiatric medications.

“Before we embark on completing research and development for psychedelics – or, for that matter, any psychoactive substance – we should endeavor to identify what the potential safety and toxicity concerns are when they are coprescribed with other prescribed medications, over-the-counter medications, and other substances (e.g., marijuana) that people take,” Dr. McIntyre said.

A case in point – a 2017 study conducted by McIntyre and colleagues revealed “significant drug-drug interactions with cannabis, which never receives that much attention.”

Also weighing in, Albert Garcia-Romeu, PhD, assistant professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, confirmed that there is “an evidence gap” on psilocybin’s and other psychedelic drugs’ interactions with other medications.

“This has not been formally studied for a number of reasons, but mainly because psilocybin has primarily been considered a drug of abuse. Psilocybin has only recently started to be looked at as a potential medication, and as such, research on drug-drug interactions is still limited, but growing,” Dr. Garcia-Romeu told this news organization.

He noted that studies are underway to better understand potential interactions between psilocybin and other medications.

“This will allow us to better understand how psilocybin should be used medically and what types of interactions could occur with other drugs or medications,” Dr. Garcia-Romeu added.

The study had no specific funding. Dr. Sarparast, Dr. McIntyre, and Dr. Garcia-Romeu reported no relevant financial relationships.

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

Psychedelics, including psilocybin and MDMA, are promising for a variety of psychiatric disorders, but there are few data showing how these drugs interact with traditional psychiatric medications, new research shows.

“Despite prolific psychedelic research and public interest, I was surprised to see little clinical research on how psilocybin and common psychiatric treatments interact,” study investigator Aryan Sarparast, MD, department of psychiatry, Oregon Health and Science University, Portland, told this news organization.

The review was published online March 7, 2022, in Psychopharmacology.
 

Need for RCTs

The Food and Drug Administration recently granted breakthrough therapy designation to psilocybin-assisted psychotherapy for major depression and treatment-resistant depression and to MDMA-assisted psychotherapy for PTSD.

The investigators assessed the volume of available research on interactions between psychedelics and traditional psychiatric medications, such as antidepressants.

They found 40 studies dating back to 1958, including 26 randomized controlled trials, 11 case reports, and 3 epidemiologic studies.

Only one randomized clinical trial evaluated the interaction between psilocybin and the most common psychiatric treatment, SSRIs, said Dr. Sarparast.

However, this study is “reassuring and overlaps with our hypothesis that there is a low risk of psilocybin and most psychiatric drugs causing harm when combined,” he noted.

Yet all of the clinical trials exclusively included young healthy adults, who were often recruited from university campuses. “We don’t have data on what happens when a depressed person on an SSRI takes psilocybin,” said Dr. Sarparast.

He added that he is concerned that the lack of evidence on drug-drug interactions will lead some providers to require patients to be tapered off existing traditional psychiatric medications before initiation of psilocybin therapy.

This may force vulnerable patients to choose between their existing therapy and psilocybin.

In addition, patients who opt for the “DIY method” of tapering risk mental health relapse and medication withdrawal effects. “That’s a very, very tough place to be,” Dr. Sarparast said.

Ideally, Dr. Sarparast would like to see a study in which depressed patients who have been receiving long-term antidepressant treatment are randomly assigned to received low, medium, and high doses of psilocybin. “This would clarify a lot of question marks.”
 

Evidence gap

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said: “The point in this article is very well taken. Indeed, more research is needed” on potential interactions between psychedelics and traditional psychiatric medications.

“Before we embark on completing research and development for psychedelics – or, for that matter, any psychoactive substance – we should endeavor to identify what the potential safety and toxicity concerns are when they are coprescribed with other prescribed medications, over-the-counter medications, and other substances (e.g., marijuana) that people take,” Dr. McIntyre said.

A case in point – a 2017 study conducted by McIntyre and colleagues revealed “significant drug-drug interactions with cannabis, which never receives that much attention.”

Also weighing in, Albert Garcia-Romeu, PhD, assistant professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, confirmed that there is “an evidence gap” on psilocybin’s and other psychedelic drugs’ interactions with other medications.

“This has not been formally studied for a number of reasons, but mainly because psilocybin has primarily been considered a drug of abuse. Psilocybin has only recently started to be looked at as a potential medication, and as such, research on drug-drug interactions is still limited, but growing,” Dr. Garcia-Romeu told this news organization.

He noted that studies are underway to better understand potential interactions between psilocybin and other medications.

“This will allow us to better understand how psilocybin should be used medically and what types of interactions could occur with other drugs or medications,” Dr. Garcia-Romeu added.

The study had no specific funding. Dr. Sarparast, Dr. McIntyre, and Dr. Garcia-Romeu reported no relevant financial relationships.

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

Psychedelics, including psilocybin and MDMA, are promising for a variety of psychiatric disorders, but there are few data showing how these drugs interact with traditional psychiatric medications, new research shows.

“Despite prolific psychedelic research and public interest, I was surprised to see little clinical research on how psilocybin and common psychiatric treatments interact,” study investigator Aryan Sarparast, MD, department of psychiatry, Oregon Health and Science University, Portland, told this news organization.

The review was published online March 7, 2022, in Psychopharmacology.
 

Need for RCTs

The Food and Drug Administration recently granted breakthrough therapy designation to psilocybin-assisted psychotherapy for major depression and treatment-resistant depression and to MDMA-assisted psychotherapy for PTSD.

The investigators assessed the volume of available research on interactions between psychedelics and traditional psychiatric medications, such as antidepressants.

They found 40 studies dating back to 1958, including 26 randomized controlled trials, 11 case reports, and 3 epidemiologic studies.

Only one randomized clinical trial evaluated the interaction between psilocybin and the most common psychiatric treatment, SSRIs, said Dr. Sarparast.

However, this study is “reassuring and overlaps with our hypothesis that there is a low risk of psilocybin and most psychiatric drugs causing harm when combined,” he noted.

Yet all of the clinical trials exclusively included young healthy adults, who were often recruited from university campuses. “We don’t have data on what happens when a depressed person on an SSRI takes psilocybin,” said Dr. Sarparast.

He added that he is concerned that the lack of evidence on drug-drug interactions will lead some providers to require patients to be tapered off existing traditional psychiatric medications before initiation of psilocybin therapy.

This may force vulnerable patients to choose between their existing therapy and psilocybin.

In addition, patients who opt for the “DIY method” of tapering risk mental health relapse and medication withdrawal effects. “That’s a very, very tough place to be,” Dr. Sarparast said.

Ideally, Dr. Sarparast would like to see a study in which depressed patients who have been receiving long-term antidepressant treatment are randomly assigned to received low, medium, and high doses of psilocybin. “This would clarify a lot of question marks.”
 

Evidence gap

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said: “The point in this article is very well taken. Indeed, more research is needed” on potential interactions between psychedelics and traditional psychiatric medications.

“Before we embark on completing research and development for psychedelics – or, for that matter, any psychoactive substance – we should endeavor to identify what the potential safety and toxicity concerns are when they are coprescribed with other prescribed medications, over-the-counter medications, and other substances (e.g., marijuana) that people take,” Dr. McIntyre said.

A case in point – a 2017 study conducted by McIntyre and colleagues revealed “significant drug-drug interactions with cannabis, which never receives that much attention.”

Also weighing in, Albert Garcia-Romeu, PhD, assistant professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, confirmed that there is “an evidence gap” on psilocybin’s and other psychedelic drugs’ interactions with other medications.

“This has not been formally studied for a number of reasons, but mainly because psilocybin has primarily been considered a drug of abuse. Psilocybin has only recently started to be looked at as a potential medication, and as such, research on drug-drug interactions is still limited, but growing,” Dr. Garcia-Romeu told this news organization.

He noted that studies are underway to better understand potential interactions between psilocybin and other medications.

“This will allow us to better understand how psilocybin should be used medically and what types of interactions could occur with other drugs or medications,” Dr. Garcia-Romeu added.

The study had no specific funding. Dr. Sarparast, Dr. McIntyre, and Dr. Garcia-Romeu reported no relevant financial relationships.

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

Before working to create standards for electronic prior authorization, the entire process itself needs some work.

That was the message from groups representing physicians, medical practices, and hospitals in response to a request for input from the Office of the National Coordinator for Health Information Technology (ONC). In January, ONC requested public feedback on how making the process for insurer approvals digital can “ease the burden of prior authorization tasks on patients, providers, and payers.”

According to a study conducted by America’s Health Insurance Plans, 71% of providers who implemented electronic prior authorization experienced “faster time to patient care.” The organization, which represents many of the nation’s health insurers, also reported that electronic prior authorization reduced the time it took to receive a decision by a health plan by 69%.

In its response to ONC, the American Association of Family Physicians (AAFP) called out prior authorization as a “leading cause of physician burden” and wrote that the organization is “strongly supportive of efforts to reform and streamline the prior authorization process.”

AAFP, which represents 127,600 family physicians, residents, and students, cited in its comments an AMA survey in which 88% of physicians said that prior authorization “generates high or extremely high administrative burden” for their practices. Practices are responsible for an average of 41 prior authorizations per physician each week, which can take almost 2 days of a physician’s time each week, according to the AAFP.

Delayed care, increased confusion, reduced treatment adherence, and even discontinuation of treatment are some of the harms prior authorization causes patients, wrote AAFP board chair Ada D. Stewart, MD.

Electronic prior authorization is “just one step in addressing the flaws of utilization management practices, and comprehensive reform is needed to reduce the volume of prior authorizations and ensure patients’ timely access to care,” wrote Dr. Stewart.
 

AHA: Most common prior auth means are phones, fax

The American Hospital Association (AHA) highlighted the variety of prior authorization requests from different payers, writing, “While some plans accept electronic means, the most common method remains using fax machines and contacting call centers, with regular hold times of 20 to 30 minutes.”

The AHA’s Senior Vice President Ashley Thompson wrote that the various prior authorization processes required by payers take up staff time and increase the chance of data entry errors.

To fix this, the AHA calls for an “end-to-end automated prior authorization process that integrates with clinicians’ EHR workflow.” According to the AHA, this approach can help physicians have access to the required prior authorization information during treatment planning.

In response to the federal agency’s question about the functional capabilities for certified health IT modules to facilitate electronic prior authorization, the AAFP wrote that the standards should include communicating to providers the expected timeline from a payer on a response, the ability to access payers’ reasoning for denials, and the creation of a process for appealing decisions.

The ONC also asked for input on the use of three fast health care interoperability resources (FHIR)–based Da Vinci implementation guides in electronic prior authorization.

Developed by the Da Vinci Project in coordination with the HL7 Clinical Decision Support Workgroup, the FHIR-based implementation guides create a mechanism for reducing the burden on provider organizations and simplifying processes by establishing electronic versions of administrative and clinical requirements that are a part of providers’ workflow.

In its response, the AHA requested that prior authorization solutions “be fully developed and tested prior to wide scale industry rollout.”

The AAFP largely agreed with the AHA in its response, writing, “Only standards and [implementation guides] that have been proven effective and adoptable in real world testing should be candidates for mandatory certification and utilization, including the Da Vinci standards.”

The Medical Group Management Association (MGMA), which represents more than 60,000 medical practice administrators, executives, and leaders, supports the idea that electronic prior authorization “has the potential to decrease administrative burden through automation but only if implemented properly.”

In its comments, the MGMA called for broader reform of prior authorization. One way to accomplish that goal is by aligning electronic prior authorization standards “with payment and quality reporting programs, as well as care delivery models, to minimize burden and overhead costs.”

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

Before working to create standards for electronic prior authorization, the entire process itself needs some work.

That was the message from groups representing physicians, medical practices, and hospitals in response to a request for input from the Office of the National Coordinator for Health Information Technology (ONC). In January, ONC requested public feedback on how making the process for insurer approvals digital can “ease the burden of prior authorization tasks on patients, providers, and payers.”

According to a study conducted by America’s Health Insurance Plans, 71% of providers who implemented electronic prior authorization experienced “faster time to patient care.” The organization, which represents many of the nation’s health insurers, also reported that electronic prior authorization reduced the time it took to receive a decision by a health plan by 69%.

In its response to ONC, the American Association of Family Physicians (AAFP) called out prior authorization as a “leading cause of physician burden” and wrote that the organization is “strongly supportive of efforts to reform and streamline the prior authorization process.”

AAFP, which represents 127,600 family physicians, residents, and students, cited in its comments an AMA survey in which 88% of physicians said that prior authorization “generates high or extremely high administrative burden” for their practices. Practices are responsible for an average of 41 prior authorizations per physician each week, which can take almost 2 days of a physician’s time each week, according to the AAFP.

Delayed care, increased confusion, reduced treatment adherence, and even discontinuation of treatment are some of the harms prior authorization causes patients, wrote AAFP board chair Ada D. Stewart, MD.

Electronic prior authorization is “just one step in addressing the flaws of utilization management practices, and comprehensive reform is needed to reduce the volume of prior authorizations and ensure patients’ timely access to care,” wrote Dr. Stewart.
 

AHA: Most common prior auth means are phones, fax

The American Hospital Association (AHA) highlighted the variety of prior authorization requests from different payers, writing, “While some plans accept electronic means, the most common method remains using fax machines and contacting call centers, with regular hold times of 20 to 30 minutes.”

The AHA’s Senior Vice President Ashley Thompson wrote that the various prior authorization processes required by payers take up staff time and increase the chance of data entry errors.

To fix this, the AHA calls for an “end-to-end automated prior authorization process that integrates with clinicians’ EHR workflow.” According to the AHA, this approach can help physicians have access to the required prior authorization information during treatment planning.

In response to the federal agency’s question about the functional capabilities for certified health IT modules to facilitate electronic prior authorization, the AAFP wrote that the standards should include communicating to providers the expected timeline from a payer on a response, the ability to access payers’ reasoning for denials, and the creation of a process for appealing decisions.

The ONC also asked for input on the use of three fast health care interoperability resources (FHIR)–based Da Vinci implementation guides in electronic prior authorization.

Developed by the Da Vinci Project in coordination with the HL7 Clinical Decision Support Workgroup, the FHIR-based implementation guides create a mechanism for reducing the burden on provider organizations and simplifying processes by establishing electronic versions of administrative and clinical requirements that are a part of providers’ workflow.

In its response, the AHA requested that prior authorization solutions “be fully developed and tested prior to wide scale industry rollout.”

The AAFP largely agreed with the AHA in its response, writing, “Only standards and [implementation guides] that have been proven effective and adoptable in real world testing should be candidates for mandatory certification and utilization, including the Da Vinci standards.”

The Medical Group Management Association (MGMA), which represents more than 60,000 medical practice administrators, executives, and leaders, supports the idea that electronic prior authorization “has the potential to decrease administrative burden through automation but only if implemented properly.”

In its comments, the MGMA called for broader reform of prior authorization. One way to accomplish that goal is by aligning electronic prior authorization standards “with payment and quality reporting programs, as well as care delivery models, to minimize burden and overhead costs.”

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

Before working to create standards for electronic prior authorization, the entire process itself needs some work.

That was the message from groups representing physicians, medical practices, and hospitals in response to a request for input from the Office of the National Coordinator for Health Information Technology (ONC). In January, ONC requested public feedback on how making the process for insurer approvals digital can “ease the burden of prior authorization tasks on patients, providers, and payers.”

According to a study conducted by America’s Health Insurance Plans, 71% of providers who implemented electronic prior authorization experienced “faster time to patient care.” The organization, which represents many of the nation’s health insurers, also reported that electronic prior authorization reduced the time it took to receive a decision by a health plan by 69%.

In its response to ONC, the American Association of Family Physicians (AAFP) called out prior authorization as a “leading cause of physician burden” and wrote that the organization is “strongly supportive of efforts to reform and streamline the prior authorization process.”

AAFP, which represents 127,600 family physicians, residents, and students, cited in its comments an AMA survey in which 88% of physicians said that prior authorization “generates high or extremely high administrative burden” for their practices. Practices are responsible for an average of 41 prior authorizations per physician each week, which can take almost 2 days of a physician’s time each week, according to the AAFP.

Delayed care, increased confusion, reduced treatment adherence, and even discontinuation of treatment are some of the harms prior authorization causes patients, wrote AAFP board chair Ada D. Stewart, MD.

Electronic prior authorization is “just one step in addressing the flaws of utilization management practices, and comprehensive reform is needed to reduce the volume of prior authorizations and ensure patients’ timely access to care,” wrote Dr. Stewart.
 

AHA: Most common prior auth means are phones, fax

The American Hospital Association (AHA) highlighted the variety of prior authorization requests from different payers, writing, “While some plans accept electronic means, the most common method remains using fax machines and contacting call centers, with regular hold times of 20 to 30 minutes.”

The AHA’s Senior Vice President Ashley Thompson wrote that the various prior authorization processes required by payers take up staff time and increase the chance of data entry errors.

To fix this, the AHA calls for an “end-to-end automated prior authorization process that integrates with clinicians’ EHR workflow.” According to the AHA, this approach can help physicians have access to the required prior authorization information during treatment planning.

In response to the federal agency’s question about the functional capabilities for certified health IT modules to facilitate electronic prior authorization, the AAFP wrote that the standards should include communicating to providers the expected timeline from a payer on a response, the ability to access payers’ reasoning for denials, and the creation of a process for appealing decisions.

The ONC also asked for input on the use of three fast health care interoperability resources (FHIR)–based Da Vinci implementation guides in electronic prior authorization.

Developed by the Da Vinci Project in coordination with the HL7 Clinical Decision Support Workgroup, the FHIR-based implementation guides create a mechanism for reducing the burden on provider organizations and simplifying processes by establishing electronic versions of administrative and clinical requirements that are a part of providers’ workflow.

In its response, the AHA requested that prior authorization solutions “be fully developed and tested prior to wide scale industry rollout.”

The AAFP largely agreed with the AHA in its response, writing, “Only standards and [implementation guides] that have been proven effective and adoptable in real world testing should be candidates for mandatory certification and utilization, including the Da Vinci standards.”

The Medical Group Management Association (MGMA), which represents more than 60,000 medical practice administrators, executives, and leaders, supports the idea that electronic prior authorization “has the potential to decrease administrative burden through automation but only if implemented properly.”

In its comments, the MGMA called for broader reform of prior authorization. One way to accomplish that goal is by aligning electronic prior authorization standards “with payment and quality reporting programs, as well as care delivery models, to minimize burden and overhead costs.”

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

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.

The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.

Is the use of chemo in this patient population merely a “graceless” means of achieving ovarian function suppression, as one expert argued in a recent debate?

Or does it offer a distinct cytotoxic benefit, as the other expert countered?

The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.

The controversy had arisen the previous year over results from the RxPONDER trial.

Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.

However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).

The results were immediately controversial.

Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.

Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.

“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.

“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.

But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.

Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”

For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”

“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”

But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
 

Debate rages on

The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”

At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.

Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.

Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”

The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?

Yes, argued Michael Gnant, MD, from the Medical University of Vienna.

Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.

Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.

“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”

The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”

So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.

But the real question is: “What does it mean for clinical practice?”

Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.

Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.

On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.

“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.

Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”

She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.

The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.

Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.

“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.

“I think both are needed in young premenopausal patients,” she added.
 

Audience responses

After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.

However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.

When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.

A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.

From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.

In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”

Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”

Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”

Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.

Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.

Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.

He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.

Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”

A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.

Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.

He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
 

Treating individual patients

When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”

For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.

For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.

“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”

“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”

This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.

The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”

“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.

Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”

These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.

Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.

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

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.

Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.

By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.

The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.

Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.

Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”

The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”

The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.

Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”

The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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

A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.

People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.

S_Bachstroem/Getty Images

In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.

In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.

Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”

Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.

UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.

“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.

The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.

The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.

“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”

But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”

Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”

Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
 

Benefits with or without known heart disease

The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.

Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).

The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).

A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).

Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).

In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.

The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).

Potential mechanisms, study limitations

“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”

Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.

However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.

They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.

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