Clinician Reviews

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

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

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

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

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

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

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

TOPLINE:

Among patients with type 1 diabetes, glycemic control may worsen in the 2 weeks after a heat wave, according to research published online May 17 in Science of The Total Environment.

METHODOLOGY:

Researchers in Spain analyzed data from 2,701 adults with type 1 diabetes who had been using intermittently scanned continuous glucose monitoring (CGM) devices during a 2022 heat wave (July 9-26) and 14 days after. Extreme heat claimed nearly 62,000 lives across Europe in the summer of 2022.

TAKEAWAY:

Time in range (between 70 mg/dL and 180 mg/dL of interstitial glucose) decreased by 4%, from 60.8% during the heat wave to 54.8% after (P < .001).

Patients who scanned their CGM results the most during the heat wave (more than 13 scans per day) scanned less often after the weather broke (1.8 fewer scans per day) and experienced the biggest drop in time in range (−5.4%).

More patients met all time-in-range recommendations during the heat wave (10.6% vs. 8.4%, P < .001).
 

IN PRACTICE:

“We hypothesized that people with diabetes, who are highly vulnerable, have more time for self-management as they spend more time indoors,” study author Jesús Moreno Fernández, MD, PhD, said in an interview. “During the COVID-19 pandemic, something similar was observed among people with diabetes.”

SOURCE:

Moreno Fernández, with the department of endocrinology and nutrition at Ciudad Real General University Hospital in Spain, is the study’s lead author.

LIMITATIONS:

The CGM data were anonymized, so researchers could not examine how individual patient factors like sex, education, or treatment type may have influenced outcomes. Temperatures remained higher than usual even after the heat wave. Worsening glycemic control could be interpreted as a lag effect of prolonged heat exposure, the researchers note.

DISCLOSURES:

The authors reported no conflicts of interest.

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

TOPLINE:

Among patients with type 1 diabetes, glycemic control may worsen in the 2 weeks after a heat wave, according to research published online May 17 in Science of The Total Environment.

METHODOLOGY:

Researchers in Spain analyzed data from 2,701 adults with type 1 diabetes who had been using intermittently scanned continuous glucose monitoring (CGM) devices during a 2022 heat wave (July 9-26) and 14 days after. Extreme heat claimed nearly 62,000 lives across Europe in the summer of 2022.

TAKEAWAY:

Time in range (between 70 mg/dL and 180 mg/dL of interstitial glucose) decreased by 4%, from 60.8% during the heat wave to 54.8% after (P < .001).

Patients who scanned their CGM results the most during the heat wave (more than 13 scans per day) scanned less often after the weather broke (1.8 fewer scans per day) and experienced the biggest drop in time in range (−5.4%).

More patients met all time-in-range recommendations during the heat wave (10.6% vs. 8.4%, P < .001).
 

IN PRACTICE:

“We hypothesized that people with diabetes, who are highly vulnerable, have more time for self-management as they spend more time indoors,” study author Jesús Moreno Fernández, MD, PhD, said in an interview. “During the COVID-19 pandemic, something similar was observed among people with diabetes.”

SOURCE:

Moreno Fernández, with the department of endocrinology and nutrition at Ciudad Real General University Hospital in Spain, is the study’s lead author.

LIMITATIONS:

The CGM data were anonymized, so researchers could not examine how individual patient factors like sex, education, or treatment type may have influenced outcomes. Temperatures remained higher than usual even after the heat wave. Worsening glycemic control could be interpreted as a lag effect of prolonged heat exposure, the researchers note.

DISCLOSURES:

The authors reported no conflicts of interest.

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

TOPLINE:

Among patients with type 1 diabetes, glycemic control may worsen in the 2 weeks after a heat wave, according to research published online May 17 in Science of The Total Environment.

METHODOLOGY:

Researchers in Spain analyzed data from 2,701 adults with type 1 diabetes who had been using intermittently scanned continuous glucose monitoring (CGM) devices during a 2022 heat wave (July 9-26) and 14 days after. Extreme heat claimed nearly 62,000 lives across Europe in the summer of 2022.

TAKEAWAY:

Time in range (between 70 mg/dL and 180 mg/dL of interstitial glucose) decreased by 4%, from 60.8% during the heat wave to 54.8% after (P < .001).

Patients who scanned their CGM results the most during the heat wave (more than 13 scans per day) scanned less often after the weather broke (1.8 fewer scans per day) and experienced the biggest drop in time in range (−5.4%).

More patients met all time-in-range recommendations during the heat wave (10.6% vs. 8.4%, P < .001).
 

IN PRACTICE:

“We hypothesized that people with diabetes, who are highly vulnerable, have more time for self-management as they spend more time indoors,” study author Jesús Moreno Fernández, MD, PhD, said in an interview. “During the COVID-19 pandemic, something similar was observed among people with diabetes.”

SOURCE:

Moreno Fernández, with the department of endocrinology and nutrition at Ciudad Real General University Hospital in Spain, is the study’s lead author.

LIMITATIONS:

The CGM data were anonymized, so researchers could not examine how individual patient factors like sex, education, or treatment type may have influenced outcomes. Temperatures remained higher than usual even after the heat wave. Worsening glycemic control could be interpreted as a lag effect of prolonged heat exposure, the researchers note.

DISCLOSURES:

The authors reported no conflicts of interest.

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

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

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

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

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

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

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

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

Chronic constipation may be associated with worsening cognitive function, new data from three prospective cohort studies with more than 100,000 adults show.

Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.

“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.

The findings were presented at the Alzheimer’s Association International Conference.
 

Prevent constipation, improve brain health?

It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.

Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.

However, few studies have investigated variations in intestinal motility and cognitive function.

“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.

The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).

Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.

The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).

Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).

The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.

Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).

These relationships were generally consistent across the three cohorts and subgroups.

“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.

“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.

The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.

They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.

“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
 

Interconnected systems

Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”

Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”

In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.

“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.

The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.

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

Chronic constipation may be associated with worsening cognitive function, new data from three prospective cohort studies with more than 100,000 adults show.

Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.

“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.

The findings were presented at the Alzheimer’s Association International Conference.
 

Prevent constipation, improve brain health?

It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.

Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.

However, few studies have investigated variations in intestinal motility and cognitive function.

“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.

The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).

Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.

The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).

Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).

The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.

Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).

These relationships were generally consistent across the three cohorts and subgroups.

“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.

“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.

The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.

They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.

“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
 

Interconnected systems

Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”

Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”

In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.

“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.

The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.

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

Chronic constipation may be associated with worsening cognitive function, new data from three prospective cohort studies with more than 100,000 adults show.

Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.

“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.

The findings were presented at the Alzheimer’s Association International Conference.
 

Prevent constipation, improve brain health?

It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.

Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.

However, few studies have investigated variations in intestinal motility and cognitive function.

“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.

The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).

Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.

The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).

Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).

The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.

Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).

These relationships were generally consistent across the three cohorts and subgroups.

“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.

“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.

The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.

They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.

“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
 

Interconnected systems

Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”

Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”

In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.

“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.

The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

Nearly 90% of diabetes management in the United States is provided by primary care clinicians; diabetes is the fifth most common reason for a primary care visit. State-of-the-art technology such as continuous glucose monitors (CGMs) will inevitably transform the management of diabetes in primary care. Clinicians and staff must be ready to educate, counsel, and support primary care patients in the use of CGMs.

CGMs (also called glucose sensors) are small, minimally invasive devices that attach to the skin of the upper arm or trunk. A tiny electrode in the subcutaneous space prompts an enzyme reaction that measures the interstitial (rather than blood) glucose concentration, typically every 5 minutes. The results are displayed on an accompanying reader or transmitted to an app on the user’s mobile phone.

CGMs could eliminate the need for finger-stick blood glucose testing, which until now, has been the much-despised gold standard for self-monitoring of glucose levels in diabetes. Despite being relatively inexpensive and accurate, finger-stick glucose tests are inconvenient and often painful. But of greater significance is this downside: Finger-stick monitoring reveals the patient’s blood glucose concentration at a single point in time, which can be difficult to interpret. Is the blood glucose rising or falling? Multiple finger-stick tests are required to determine the trend of a patient’s glucose levels or the response to food or exercise.

In contrast, the graphic display from a CGM sensor is more like a movie, telling a story as it unfolds. Uninterrupted data provide valuable feedback to patients about the effects of diet, physical activity, stress, or pain on their glucose levels. And for the first time, it’s easy to determine the proportion of time the patient spends in or out of the target glucose range.

Incorporating new technology into your practice may seem like a burden, but the reward is better information that leads to better management of diabetes. If you’re new to glucose sensors, many excellent resources are available to learn how to use them.

I recommend starting with a website called diabeteswise.org, which has both a patient-facing and clinician-facing version. This unbranded site serves as a kind of Consumer Reports for diabetes technology, allowing both patients and professionals to compare and contrast currently available CGM devices.

DiabetesWisePro  has information ranging from CGM device fundamentals and best practices to CGM prescribing and reimbursement.

Clinical Diabetes also provides multiple tools to help incorporate these devices into primary care clinical practice, including:

• Continuous Glucose Monitoring: Optimizing Diabetes Care (CME course).

• Diabetes Technology in Primary Care.

The next article in this series will cover two types of CGMs used in primary care: professional and personal devices.

Dr. Shubrook is a professor in the department of primary care, Touro University California College of Osteopathic Medicine, Vallejo, Calif., and director of diabetes services, Solano County Family Health Services, Fairfield, Calif. He disclosed ties with Abbott, Astra Zeneca, Bayer, Nevro, and Novo Nordisk.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.