It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.
 

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Noninvasive prenatal screening

Cell-free DNA testing, or noninvasive prenatal testing (NIPT), is a powerful noninvasive screening technology for aneuploidy that analyzes fetal DNA floating freely in maternal blood starting at about 9-10 weeks of pregnancy. However, it is not a substitute for invasive testing and is not diagnostic.

Patients we see are commonly misinformed that a negative cell-free DNA testing result means their baby is without doubt unaffected by a chromosomal abnormality. NIPT is the most sensitive and specific screening test for the common fetal aneuploidies (trisomies 13, 18, and 21), with a significantly better positive predictive value than previous noninvasive chromosome screening. However, NIPT findings still include false-negative results and some false-positive results. Patients must be counseled that NIPT does not offer absolute findings.

Courtesy Dr. Shifa Turan

Microarray analysis, variants of unknown significance (VUS)

Chromosomal microarray analysis of DNA from a chorionic villus sampling or amniocentesis specimen enables prenatal detection of exceptionally small genomic deletions and duplications – tiny chunks of DNA – that cannot be seen with standard karyotype testing.

That microdeletions and microduplications can produce abnormalities and conditions that can be significantly more severe than the absence or addition of entire chromosomes is not necessarily intuitive. It is as if the entire plot of a book is revealed in just one page.

For instance, Turner syndrome results when one of the X chromosomes is entirely missing. (Occasionally, there is a large, partial absence.) The absence can cause a variety of symptoms, including failure of the ovaries to develop and heart defects, but most affected individuals can lead healthy and independent lives with the only features being short stature and a wide neck.

Angelman syndrome, in contrast, is most often caused by a microdeletion of genetic material from chromosome 15 – a tiny snip of the chromosome – but results in ataxia, severe intellectual disability, lifelong seizures, and severe lifelong speech impairment.

In our program, we counsel patients before testing that results may come back one of three ways: completely normal, definitely abnormal, or with a VUS.

A VUS is a challenging finding because it represents a loss or gain of a small portion of a chromosome with unclear clinical significance. In some cases, the uncertainty stems from the microdeletion or duplication not having been seen before — or not seen enough to be accurately characterized as benign or pathogenic. In other cases, the uncertainty stems from an associated phenotype that is highly variable. Either way, a VUS often makes the investigation for genetic conditions and subsequent decision-making more difficult, and a genetic counselor’s expertise and guidance is needed.
 

Advances in imaging, panel testing

The most significant addition to the first-trimester ultrasound evaluation in recent years has been the systematic assessment of the fetal circulation and the structure of the fetal heart, with early detection of the most common forms of birth defects.

Structural assessment of the central nervous system, abdomen, and skeleton is also now possible during the first-trimester ultrasound and offers the opportunity for early genetic assessment when anomalies are detected.

Ultrasound imaging in the second and third trimesters can help refine the diagnosis of birth defects, track the evolution of suspicious findings from the first trimester, or uncover anomalies that did not present earlier. Findings may be suggestive of underlying genetic conditions and drive the use of “panel” tests, or targeted sequencing panels, to help make a diagnosis.

Features of skeletal dysplasia, for instance, would lead the genetic counselor to recommend a panel of tests that target skeletal dysplasia-associated genes, looking for genetic mutations. Similarly, holoprosencephaly detected on ultrasound could prompt use of a customized gene panel to look for mutations in a series of different genes known to cause the anomaly.

Second trimester details that may guide genetic investigation are not limited to ultrasound. In certain instances, MRI has the unique capability to diagnose particular structural defects, especially brain anomalies with developmental specificity.
 

Commentary by Christopher R. Harman, MD

Genetic counseling is now a mandatory part of all pregnancy evaluation programs. Counselors not only explain and interpret tests and results to families but also, increasingly, guide the efforts of the obstetrics team, including the maternal-fetal medicine specialist.

The genetic counselor helps design screening for the whole patient population and focuses diagnostic testing in specific cases of screening concerns, family history, chromosomal abnormalities in prior pregnancies, and fetal abnormalities detected through ultrasonography or other prenatal surveillance. They also serve as a crucial link between the physician and the family.

The counselor also has a key role in the case of a stillbirth or other adverse pregnancy outcome in investigating possible genetic elements and working with the family on evaluation of recurrence risk and prevention of a similar outcome in future pregnancies. The details of poor outcomes hold the potential for making the next pregnancy successful.
 

Commentary by Amanda S. Higgs, MGC

Even in 2021, there is no “perfect baby test.” Patients can have expanded carrier screening, cell-free DNA testing, invasive testing with microarray, and all of the available imaging, with normal results, and still have a baby with a genetic disorder. Understanding the concept of residual risk is important. So is appreciation for the possibility that incidental findings – information not sought – can occur even with specific genetic testing.

Genetic counselors are there to help patients understand and assimilate information, usher them through the screening and testing process, and facilitate informed decision-making. We are nondirective in our counseling. We try to assess their values, their support systems, and their experience with disability and help them to make the best decisions for themselves regarding testing and further evaluation, as well as other reproductive decisions.

[email protected]

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Feelings of chronic emptiness and self-injury have been identified as two key risk factors for suicide attempts (SAs) in patients with borderline personality disorder (BPD), a new cross-sectional, nationally representative study suggests.

The findings also show lifetime and past-year SAs are common among patients with BPD, even when excluding self-injurious behaviors.

The results suggest that in addition to asking patients about self-harm during suicide risk screenings and assessments, clinicians should query them about “longstanding” feelings of emptiness, study investigator Carlos M. Grilo, PhD, professor of psychiatry and psychology, Yale University, New Haven, Conn., said in an interview.

Although related, chronic emptiness “is distinct and goes beyond feelings of sadness, loneliness, and hopelessness,” explained Dr. Grilo. Patients describe this emptiness as “a feeling that their life has no meaning or any real purpose,” he said.

The study was published online May 11 in JAMA Network Open.
 

Filling a research gap

While BPD and other psychiatric disorders are associated with suicide, the authors noted there is a “dearth of epidemiological research” examining the link between BPD and suicide.

Criteria for BPD diagnosis requires any five of the following criteria: relationships, affective instability, abandonment fear, anger, identity disturbance, emptiness, disassociation/paranoia, self-injurious behavior, and impulsivity, along with social-occupation dysfunction.

To determine SA risk with specific BPD diagnostic criteria, the investigators examined data on 36,309 individuals who participated in the third wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), conducted from 2012 to 2013.

During computer-assisted, face-to-face interviews, study participants answered questions based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5) of the National Institute on Alcohol Abuse and Alcoholism.

This structured interview assesses a range of DSM-5–defined psychiatric disorders and their criteria. In addition to BPD, the AUDADIS-5 generates diagnoses for mood disorders, anxiety disorders, posttraumatic stress disorder, substance use disorders, antisocial personality disorder, schizotypal disorder, and conduct disorder.

During the interviews, respondents were asked if they had ever attempted suicide. For those who had, interviewers recorded the total number of lifetime attempts.

Participants also answered questions about childhood maltreatment including physical neglect, emotional neglect, physical abuse, emotional abuse, and sexual abuse by parents or caregivers and other adverse events occurring before the age of 18.
 

Childhood trauma common

Patients with BPD frequently report a history of childhood trauma, noted Dr. Grilo, adding that such trauma is associated with self-harm and suicide attempts. Sociodemographic information, including age, sex, and ethnicity/race, education level, and income, was also gathered.

Investigators examined data on suicide attempts using relatively stringent coding that required serious dysfunction in at least five BPD criteria.

Using this definition, investigators found the lifetime SA prevalence in patients with BPD was 30.4%, and 3.2% for past-year SAs. This compared with a rate of 3.7% for lifetime SAs and 0.2% for past-year SAs in those without a BPD diagnosis.

The authors examined SA rates using diagnostic codes in the NESARC-III that required seriously impaired function in only 1 or 2 BPD criteria. Rates were higher using the 5-criteria definition.

When the researchers excluded the BPD criterion of self-injurious behavior, the prevalence was 28.1% for lifetime and 3.0% for past-year SAs among the BPD group, with corresponding rates of 3.8% and 0.2% in those without a BPD diagnosis.

It’s important to look at this, said Dr. Grilo, as some patients with BPD who engage in self-harm have suicidal intent while others don’t.

“We tested whether BPD had heightened risk for suicide attempts if we eliminated the self-injurious criterion and we found that heightened risk was still there,” he explained.

Looking at individual criteria for BPD, a model that adjusted for sociodemographic characteristics, other psychiatric disorders, age at BPD onset, and history of childhood adverse events uncovered two criteria that were significantly associated with increased odds of SAs.

One was emptiness. For lifetime suicide attempts, the adjusted odds ratio (aOR) was 1.58 (95% confidence interval, 1.16-2.14) and for past-year attempts, the aOR was 1.99 (95% CI, 1.08-3.66).

The second was self-injurious behavior. For lifetime attempts, the aOR was 24.28 (95% CI, 16.83-32.03) and for past-year attempts, the aOR was 19.32 (95% CI, 5.22-71.58).

In a model in which all BPD-specific criteria were entered while excluding self-injurious behavior, the aORs for emptiness were 1.66 (95% CI, 1.23-2.24) for lifetime suicide attempts and 2.45 (95% CI, 1.18-5.08) for past year attempts.

Unlike another recent study that included more than 700 treatment-seeking patients with BPD who were followed for 10 years, the current study did not show significant associations with SAs for two other BPD criteria – identity disturbance and frantic attempts to avoid abandonment.

Dr. Grilo explained this might be because the earlier study included treatment-seeking patients instead of community cases, or because of differences in assessment interviews or other factors.
 

‘Compelling evidence’

“Our epidemiological sample has much broader generalizability and fewer potential confounds than the clinical treatment-seeking sample,” said Dr. Grilo.

However, he noted that the two studies “converge strongly and provide compelling evidence that BPD is associated with substantially heightened risk for suicide attempts over the lifetime.”

The two studies “also converge in finding that the presence of symptoms such as repeated self-harm and feelings of chronic emptiness are also associated with risk for suicide attempts.”

The new findings highlight the need to ask potentially at-risk patients about feelings of emptiness as well as self-injurious behaviors. Clinicians could, for example, ask: “Have you often felt like your life had no purpose or meaning?” or “Have you often felt empty inside?”

Limitations of the study include reliance on retrospective self-reports and use of lay interviewers, although these interviewers were trained and had an average of 5 years of experience conducting health-related surveys.

Although the study included a representative sample of U.S. adults, the sample did not include groups known to have high rates of suicide and self-harm behaviors, such as institutionalized, incarcerated, or homeless individuals.

In addition, the study did not evaluate severity and duration of BPD, although the authors noted they did adjust for age at BPD onset, this did not alter the findings.
 

Often misdiagnosed

Commenting on the study, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, and past-president, American Psychiatric Association, and an expert on BPD, had high praise for the research.

BPD is often misdiagnosed, Dr. Oldham said in an interview. Many patients seek help from primary care doctors who may label the symptoms as an anxiety disorder or a mood disorder, he said.

Although medications can help treat some BPD symptoms, “the primary, core evidence-based treatment for BPD is psychotherapy,” said Dr. Oldham, who some years ago helped develop evidence-based practice guidelines for BPD.

“It’s a clear and very well-designed study, and I don’t see any major limitations or problems with it,” he said. “The authors kept their focus rigorously on their goals and they used really careful methodology.”

He noted the “huge” numbers of patients included in the data and the relatively large percentage of men (43.7%).

“There’s a general belief that it’s mostly females who have BPD, but that’s not true; it’s females who come to treatment,” said Dr. Oldham.

Requiring that all five criteria lead to seriously impaired functioning “is a much more rigorous diagnostic methodology” than requiring only one or two criteria to lead to such impairment, said Dr. Oldham. “This is really important” and makes it “a much stronger study.”

The finding that self-harm behavior was linked to suicide attempts isn’t that surprising as this association has been well documented, but the finding that chronic emptiness is also predictive of future suicide attempts “is news,” said Dr. Oldham.

“We have not paid enough attention to this criterion in the clinical world or in the research world.”

Dr. Oldham said one patient with BPD gave him an ideal metaphor for emptiness. “She said it’s like there’s just nobody home. Think of it as an empty house that may look fine on the outside but you go inside and nobody lives there; there’s no furniture; no favorite things; no photos; no possessions.”

The authors have “important messages we need to pay attention to, and the main one is to explore this sense of chronic ‘nobody home’ emptiness,” said Dr. Oldham.

Dr. Grilo has reported receiving research grants from the National Institutes of Health; serving as a consultant for Sunovion and Weight Watchers; receiving honoraria for lectures, continuing medical education activities, and presentations at scientific conferences; and receiving royalties from Guilford Press and Taylor & Francis, all outside the submitted work.

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

Feelings of chronic emptiness and self-injury have been identified as two key risk factors for suicide attempts (SAs) in patients with borderline personality disorder (BPD), a new cross-sectional, nationally representative study suggests.

The findings also show lifetime and past-year SAs are common among patients with BPD, even when excluding self-injurious behaviors.

The results suggest that in addition to asking patients about self-harm during suicide risk screenings and assessments, clinicians should query them about “longstanding” feelings of emptiness, study investigator Carlos M. Grilo, PhD, professor of psychiatry and psychology, Yale University, New Haven, Conn., said in an interview.

Although related, chronic emptiness “is distinct and goes beyond feelings of sadness, loneliness, and hopelessness,” explained Dr. Grilo. Patients describe this emptiness as “a feeling that their life has no meaning or any real purpose,” he said.

The study was published online May 11 in JAMA Network Open.
 

Filling a research gap

While BPD and other psychiatric disorders are associated with suicide, the authors noted there is a “dearth of epidemiological research” examining the link between BPD and suicide.

Criteria for BPD diagnosis requires any five of the following criteria: relationships, affective instability, abandonment fear, anger, identity disturbance, emptiness, disassociation/paranoia, self-injurious behavior, and impulsivity, along with social-occupation dysfunction.

To determine SA risk with specific BPD diagnostic criteria, the investigators examined data on 36,309 individuals who participated in the third wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), conducted from 2012 to 2013.

During computer-assisted, face-to-face interviews, study participants answered questions based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5) of the National Institute on Alcohol Abuse and Alcoholism.

This structured interview assesses a range of DSM-5–defined psychiatric disorders and their criteria. In addition to BPD, the AUDADIS-5 generates diagnoses for mood disorders, anxiety disorders, posttraumatic stress disorder, substance use disorders, antisocial personality disorder, schizotypal disorder, and conduct disorder.

During the interviews, respondents were asked if they had ever attempted suicide. For those who had, interviewers recorded the total number of lifetime attempts.

Participants also answered questions about childhood maltreatment including physical neglect, emotional neglect, physical abuse, emotional abuse, and sexual abuse by parents or caregivers and other adverse events occurring before the age of 18.
 

Childhood trauma common

Patients with BPD frequently report a history of childhood trauma, noted Dr. Grilo, adding that such trauma is associated with self-harm and suicide attempts. Sociodemographic information, including age, sex, and ethnicity/race, education level, and income, was also gathered.

Investigators examined data on suicide attempts using relatively stringent coding that required serious dysfunction in at least five BPD criteria.

Using this definition, investigators found the lifetime SA prevalence in patients with BPD was 30.4%, and 3.2% for past-year SAs. This compared with a rate of 3.7% for lifetime SAs and 0.2% for past-year SAs in those without a BPD diagnosis.

The authors examined SA rates using diagnostic codes in the NESARC-III that required seriously impaired function in only 1 or 2 BPD criteria. Rates were higher using the 5-criteria definition.

When the researchers excluded the BPD criterion of self-injurious behavior, the prevalence was 28.1% for lifetime and 3.0% for past-year SAs among the BPD group, with corresponding rates of 3.8% and 0.2% in those without a BPD diagnosis.

It’s important to look at this, said Dr. Grilo, as some patients with BPD who engage in self-harm have suicidal intent while others don’t.

“We tested whether BPD had heightened risk for suicide attempts if we eliminated the self-injurious criterion and we found that heightened risk was still there,” he explained.

Looking at individual criteria for BPD, a model that adjusted for sociodemographic characteristics, other psychiatric disorders, age at BPD onset, and history of childhood adverse events uncovered two criteria that were significantly associated with increased odds of SAs.

One was emptiness. For lifetime suicide attempts, the adjusted odds ratio (aOR) was 1.58 (95% confidence interval, 1.16-2.14) and for past-year attempts, the aOR was 1.99 (95% CI, 1.08-3.66).

The second was self-injurious behavior. For lifetime attempts, the aOR was 24.28 (95% CI, 16.83-32.03) and for past-year attempts, the aOR was 19.32 (95% CI, 5.22-71.58).

In a model in which all BPD-specific criteria were entered while excluding self-injurious behavior, the aORs for emptiness were 1.66 (95% CI, 1.23-2.24) for lifetime suicide attempts and 2.45 (95% CI, 1.18-5.08) for past year attempts.

Unlike another recent study that included more than 700 treatment-seeking patients with BPD who were followed for 10 years, the current study did not show significant associations with SAs for two other BPD criteria – identity disturbance and frantic attempts to avoid abandonment.

Dr. Grilo explained this might be because the earlier study included treatment-seeking patients instead of community cases, or because of differences in assessment interviews or other factors.
 

‘Compelling evidence’

“Our epidemiological sample has much broader generalizability and fewer potential confounds than the clinical treatment-seeking sample,” said Dr. Grilo.

However, he noted that the two studies “converge strongly and provide compelling evidence that BPD is associated with substantially heightened risk for suicide attempts over the lifetime.”

The two studies “also converge in finding that the presence of symptoms such as repeated self-harm and feelings of chronic emptiness are also associated with risk for suicide attempts.”

The new findings highlight the need to ask potentially at-risk patients about feelings of emptiness as well as self-injurious behaviors. Clinicians could, for example, ask: “Have you often felt like your life had no purpose or meaning?” or “Have you often felt empty inside?”

Limitations of the study include reliance on retrospective self-reports and use of lay interviewers, although these interviewers were trained and had an average of 5 years of experience conducting health-related surveys.

Although the study included a representative sample of U.S. adults, the sample did not include groups known to have high rates of suicide and self-harm behaviors, such as institutionalized, incarcerated, or homeless individuals.

In addition, the study did not evaluate severity and duration of BPD, although the authors noted they did adjust for age at BPD onset, this did not alter the findings.
 

Often misdiagnosed

Commenting on the study, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, and past-president, American Psychiatric Association, and an expert on BPD, had high praise for the research.

BPD is often misdiagnosed, Dr. Oldham said in an interview. Many patients seek help from primary care doctors who may label the symptoms as an anxiety disorder or a mood disorder, he said.

Although medications can help treat some BPD symptoms, “the primary, core evidence-based treatment for BPD is psychotherapy,” said Dr. Oldham, who some years ago helped develop evidence-based practice guidelines for BPD.

“It’s a clear and very well-designed study, and I don’t see any major limitations or problems with it,” he said. “The authors kept their focus rigorously on their goals and they used really careful methodology.”

He noted the “huge” numbers of patients included in the data and the relatively large percentage of men (43.7%).

“There’s a general belief that it’s mostly females who have BPD, but that’s not true; it’s females who come to treatment,” said Dr. Oldham.

Requiring that all five criteria lead to seriously impaired functioning “is a much more rigorous diagnostic methodology” than requiring only one or two criteria to lead to such impairment, said Dr. Oldham. “This is really important” and makes it “a much stronger study.”

The finding that self-harm behavior was linked to suicide attempts isn’t that surprising as this association has been well documented, but the finding that chronic emptiness is also predictive of future suicide attempts “is news,” said Dr. Oldham.

“We have not paid enough attention to this criterion in the clinical world or in the research world.”

Dr. Oldham said one patient with BPD gave him an ideal metaphor for emptiness. “She said it’s like there’s just nobody home. Think of it as an empty house that may look fine on the outside but you go inside and nobody lives there; there’s no furniture; no favorite things; no photos; no possessions.”

The authors have “important messages we need to pay attention to, and the main one is to explore this sense of chronic ‘nobody home’ emptiness,” said Dr. Oldham.

Dr. Grilo has reported receiving research grants from the National Institutes of Health; serving as a consultant for Sunovion and Weight Watchers; receiving honoraria for lectures, continuing medical education activities, and presentations at scientific conferences; and receiving royalties from Guilford Press and Taylor & Francis, all outside the submitted work.

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

Feelings of chronic emptiness and self-injury have been identified as two key risk factors for suicide attempts (SAs) in patients with borderline personality disorder (BPD), a new cross-sectional, nationally representative study suggests.

The findings also show lifetime and past-year SAs are common among patients with BPD, even when excluding self-injurious behaviors.

The results suggest that in addition to asking patients about self-harm during suicide risk screenings and assessments, clinicians should query them about “longstanding” feelings of emptiness, study investigator Carlos M. Grilo, PhD, professor of psychiatry and psychology, Yale University, New Haven, Conn., said in an interview.

Although related, chronic emptiness “is distinct and goes beyond feelings of sadness, loneliness, and hopelessness,” explained Dr. Grilo. Patients describe this emptiness as “a feeling that their life has no meaning or any real purpose,” he said.

The study was published online May 11 in JAMA Network Open.
 

Filling a research gap

While BPD and other psychiatric disorders are associated with suicide, the authors noted there is a “dearth of epidemiological research” examining the link between BPD and suicide.

Criteria for BPD diagnosis requires any five of the following criteria: relationships, affective instability, abandonment fear, anger, identity disturbance, emptiness, disassociation/paranoia, self-injurious behavior, and impulsivity, along with social-occupation dysfunction.

To determine SA risk with specific BPD diagnostic criteria, the investigators examined data on 36,309 individuals who participated in the third wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), conducted from 2012 to 2013.

During computer-assisted, face-to-face interviews, study participants answered questions based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5) of the National Institute on Alcohol Abuse and Alcoholism.

This structured interview assesses a range of DSM-5–defined psychiatric disorders and their criteria. In addition to BPD, the AUDADIS-5 generates diagnoses for mood disorders, anxiety disorders, posttraumatic stress disorder, substance use disorders, antisocial personality disorder, schizotypal disorder, and conduct disorder.

During the interviews, respondents were asked if they had ever attempted suicide. For those who had, interviewers recorded the total number of lifetime attempts.

Participants also answered questions about childhood maltreatment including physical neglect, emotional neglect, physical abuse, emotional abuse, and sexual abuse by parents or caregivers and other adverse events occurring before the age of 18.
 

Childhood trauma common

Patients with BPD frequently report a history of childhood trauma, noted Dr. Grilo, adding that such trauma is associated with self-harm and suicide attempts. Sociodemographic information, including age, sex, and ethnicity/race, education level, and income, was also gathered.

Investigators examined data on suicide attempts using relatively stringent coding that required serious dysfunction in at least five BPD criteria.

Using this definition, investigators found the lifetime SA prevalence in patients with BPD was 30.4%, and 3.2% for past-year SAs. This compared with a rate of 3.7% for lifetime SAs and 0.2% for past-year SAs in those without a BPD diagnosis.

The authors examined SA rates using diagnostic codes in the NESARC-III that required seriously impaired function in only 1 or 2 BPD criteria. Rates were higher using the 5-criteria definition.

When the researchers excluded the BPD criterion of self-injurious behavior, the prevalence was 28.1% for lifetime and 3.0% for past-year SAs among the BPD group, with corresponding rates of 3.8% and 0.2% in those without a BPD diagnosis.

It’s important to look at this, said Dr. Grilo, as some patients with BPD who engage in self-harm have suicidal intent while others don’t.

“We tested whether BPD had heightened risk for suicide attempts if we eliminated the self-injurious criterion and we found that heightened risk was still there,” he explained.

Looking at individual criteria for BPD, a model that adjusted for sociodemographic characteristics, other psychiatric disorders, age at BPD onset, and history of childhood adverse events uncovered two criteria that were significantly associated with increased odds of SAs.

One was emptiness. For lifetime suicide attempts, the adjusted odds ratio (aOR) was 1.58 (95% confidence interval, 1.16-2.14) and for past-year attempts, the aOR was 1.99 (95% CI, 1.08-3.66).

The second was self-injurious behavior. For lifetime attempts, the aOR was 24.28 (95% CI, 16.83-32.03) and for past-year attempts, the aOR was 19.32 (95% CI, 5.22-71.58).

In a model in which all BPD-specific criteria were entered while excluding self-injurious behavior, the aORs for emptiness were 1.66 (95% CI, 1.23-2.24) for lifetime suicide attempts and 2.45 (95% CI, 1.18-5.08) for past year attempts.

Unlike another recent study that included more than 700 treatment-seeking patients with BPD who were followed for 10 years, the current study did not show significant associations with SAs for two other BPD criteria – identity disturbance and frantic attempts to avoid abandonment.

Dr. Grilo explained this might be because the earlier study included treatment-seeking patients instead of community cases, or because of differences in assessment interviews or other factors.
 

‘Compelling evidence’

“Our epidemiological sample has much broader generalizability and fewer potential confounds than the clinical treatment-seeking sample,” said Dr. Grilo.

However, he noted that the two studies “converge strongly and provide compelling evidence that BPD is associated with substantially heightened risk for suicide attempts over the lifetime.”

The two studies “also converge in finding that the presence of symptoms such as repeated self-harm and feelings of chronic emptiness are also associated with risk for suicide attempts.”

The new findings highlight the need to ask potentially at-risk patients about feelings of emptiness as well as self-injurious behaviors. Clinicians could, for example, ask: “Have you often felt like your life had no purpose or meaning?” or “Have you often felt empty inside?”

Limitations of the study include reliance on retrospective self-reports and use of lay interviewers, although these interviewers were trained and had an average of 5 years of experience conducting health-related surveys.

Although the study included a representative sample of U.S. adults, the sample did not include groups known to have high rates of suicide and self-harm behaviors, such as institutionalized, incarcerated, or homeless individuals.

In addition, the study did not evaluate severity and duration of BPD, although the authors noted they did adjust for age at BPD onset, this did not alter the findings.
 

Often misdiagnosed

Commenting on the study, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, and past-president, American Psychiatric Association, and an expert on BPD, had high praise for the research.

BPD is often misdiagnosed, Dr. Oldham said in an interview. Many patients seek help from primary care doctors who may label the symptoms as an anxiety disorder or a mood disorder, he said.

Although medications can help treat some BPD symptoms, “the primary, core evidence-based treatment for BPD is psychotherapy,” said Dr. Oldham, who some years ago helped develop evidence-based practice guidelines for BPD.

“It’s a clear and very well-designed study, and I don’t see any major limitations or problems with it,” he said. “The authors kept their focus rigorously on their goals and they used really careful methodology.”

He noted the “huge” numbers of patients included in the data and the relatively large percentage of men (43.7%).

“There’s a general belief that it’s mostly females who have BPD, but that’s not true; it’s females who come to treatment,” said Dr. Oldham.

Requiring that all five criteria lead to seriously impaired functioning “is a much more rigorous diagnostic methodology” than requiring only one or two criteria to lead to such impairment, said Dr. Oldham. “This is really important” and makes it “a much stronger study.”

The finding that self-harm behavior was linked to suicide attempts isn’t that surprising as this association has been well documented, but the finding that chronic emptiness is also predictive of future suicide attempts “is news,” said Dr. Oldham.

“We have not paid enough attention to this criterion in the clinical world or in the research world.”

Dr. Oldham said one patient with BPD gave him an ideal metaphor for emptiness. “She said it’s like there’s just nobody home. Think of it as an empty house that may look fine on the outside but you go inside and nobody lives there; there’s no furniture; no favorite things; no photos; no possessions.”

The authors have “important messages we need to pay attention to, and the main one is to explore this sense of chronic ‘nobody home’ emptiness,” said Dr. Oldham.

Dr. Grilo has reported receiving research grants from the National Institutes of Health; serving as a consultant for Sunovion and Weight Watchers; receiving honoraria for lectures, continuing medical education activities, and presentations at scientific conferences; and receiving royalties from Guilford Press and Taylor & Francis, all outside the submitted work.

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

The Foundation introduced new awards in the 2021 awards cycle addressing diversity of GI investigators and the need for GI-specific COVID-19 research.

The American Gastroenterological Association is excited to announce the 45 researchers inducted into the 2021 class of AGA Research Foundation Awards Program recipients.

In the 2021 awards cycle, the AGA Research Foundation will provide more than $2.5 million in research funding to investigators working on projects that will further enhance our understanding of gastrointestinal and liver conditions and ultimately lead to the development of better treatment options for digestive diseases patients.

“This year, we made several enhancements to our awards portfolio to address current priorities for AGA and the field – we launched a new COVID-19 research award and established a summer undergraduate research fellowship to introduce talented underrepresented minority students into GI research,” said Robert S. Sandler, MD, MPH, AGAF, chair of the AGA Research Foundation. “We continue to change our funding program to meet the needs of GI research. What does not change is our long-standing commitment to support the research careers of talented early career investigators.”

The AGA Research Foundation Awards Program recruits, retains, and supports the most promising researchers in gastroenterology and hepatology. With funding from the foundation, recipients have protected time to take their research to the next level.

View the full list of recipients online.

The AGA Research Awards Program is made possible thanks to generous donors and funders. Learn more about the AGA Research Foundation at http://foundation.gastro.org.  

The Foundation introduced new awards in the 2021 awards cycle addressing diversity of GI investigators and the need for GI-specific COVID-19 research.

The American Gastroenterological Association is excited to announce the 45 researchers inducted into the 2021 class of AGA Research Foundation Awards Program recipients.

In the 2021 awards cycle, the AGA Research Foundation will provide more than $2.5 million in research funding to investigators working on projects that will further enhance our understanding of gastrointestinal and liver conditions and ultimately lead to the development of better treatment options for digestive diseases patients.

“This year, we made several enhancements to our awards portfolio to address current priorities for AGA and the field – we launched a new COVID-19 research award and established a summer undergraduate research fellowship to introduce talented underrepresented minority students into GI research,” said Robert S. Sandler, MD, MPH, AGAF, chair of the AGA Research Foundation. “We continue to change our funding program to meet the needs of GI research. What does not change is our long-standing commitment to support the research careers of talented early career investigators.”

The AGA Research Foundation Awards Program recruits, retains, and supports the most promising researchers in gastroenterology and hepatology. With funding from the foundation, recipients have protected time to take their research to the next level.

View the full list of recipients online.

The AGA Research Awards Program is made possible thanks to generous donors and funders. Learn more about the AGA Research Foundation at http://foundation.gastro.org.  

The Foundation introduced new awards in the 2021 awards cycle addressing diversity of GI investigators and the need for GI-specific COVID-19 research.

The American Gastroenterological Association is excited to announce the 45 researchers inducted into the 2021 class of AGA Research Foundation Awards Program recipients.

In the 2021 awards cycle, the AGA Research Foundation will provide more than $2.5 million in research funding to investigators working on projects that will further enhance our understanding of gastrointestinal and liver conditions and ultimately lead to the development of better treatment options for digestive diseases patients.

“This year, we made several enhancements to our awards portfolio to address current priorities for AGA and the field – we launched a new COVID-19 research award and established a summer undergraduate research fellowship to introduce talented underrepresented minority students into GI research,” said Robert S. Sandler, MD, MPH, AGAF, chair of the AGA Research Foundation. “We continue to change our funding program to meet the needs of GI research. What does not change is our long-standing commitment to support the research careers of talented early career investigators.”

The AGA Research Foundation Awards Program recruits, retains, and supports the most promising researchers in gastroenterology and hepatology. With funding from the foundation, recipients have protected time to take their research to the next level.

View the full list of recipients online.

The AGA Research Awards Program is made possible thanks to generous donors and funders. Learn more about the AGA Research Foundation at http://foundation.gastro.org.  

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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