Mixed Topics

BALTIMORE – Training hospitals that have state or institutional abortion restrictions are less likely to follow the evidence-based standard of care in diagnosing and managing miscarriages, including taking patient preferences into account, according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.

The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.

“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”

For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
 

Reduced access leads to higher risk interventions

An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.

They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.

For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.

”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.

“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.

“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
 

Reduced access to miscarriage care options in ‘hostile’ states

Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.

The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.

At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).

Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.

Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.

Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).

In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).

Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.

“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
 

Institutional policies had the strongest impact

Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.

After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.

Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).

Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).

Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.

Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.

“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”

The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”

The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.

BALTIMORE – Training hospitals that have state or institutional abortion restrictions are less likely to follow the evidence-based standard of care in diagnosing and managing miscarriages, including taking patient preferences into account, according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.

The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.

“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”

For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
 

Reduced access leads to higher risk interventions

An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.

They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.

For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.

”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.

“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.

“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
 

Reduced access to miscarriage care options in ‘hostile’ states

Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.

The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.

At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).

Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.

Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.

Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).

In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).

Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.

“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
 

Institutional policies had the strongest impact

Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.

After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.

Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).

Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).

Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.

Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.

“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”

The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”

The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.

BALTIMORE – Training hospitals that have state or institutional abortion restrictions are less likely to follow the evidence-based standard of care in diagnosing and managing miscarriages, including taking patient preferences into account, according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.

The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.

“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”

For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
 

Reduced access leads to higher risk interventions

An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.

They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.

For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.

”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.

“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.

“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
 

Reduced access to miscarriage care options in ‘hostile’ states

Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.

The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.

At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).

Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.

Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.

Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).

In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).

Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.

“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
 

Institutional policies had the strongest impact

Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.

After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.

Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).

Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).

Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.

Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.

“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”

The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”

The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVD by ascertaining LDL-C

• The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL),estimation of LDL-C is invalid.
• The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC–HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴
• National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵
• Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

• Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴
• Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Continue to: Applying the estimate of 10-year ASCVD risk...

 

 

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

• Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

• Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention: Stratification by age

• 40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force (USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

• 20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴
• > 75 years, without ASCVD. In this group, the benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy...

 

 

Options for lipid-lowering pharmacotherapy

• Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

• Ezetimibe, a selective cholesterol-absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴
• PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23
• Inclisiran, an injectable small-interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴
• Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28
• Bempedoic acid is a small-molecule inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-intolerant patients, bempedoicacid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰
• Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL)and TG (42 mg/dL).^31,32
• Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; HDL-C< 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴ ●

CORRESPONDENCE

Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVD by ascertaining LDL-C

• The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL),estimation of LDL-C is invalid.
• The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC–HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴
• National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵
• Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

• Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴
• Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Continue to: Applying the estimate of 10-year ASCVD risk...

 

 

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

• Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

• Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention: Stratification by age

• 40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force (USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

• 20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴
• > 75 years, without ASCVD. In this group, the benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy...

 

 

Options for lipid-lowering pharmacotherapy

• Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

• Ezetimibe, a selective cholesterol-absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴
• PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23
• Inclisiran, an injectable small-interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴
• Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28
• Bempedoic acid is a small-molecule inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-intolerant patients, bempedoicacid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰
• Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL)and TG (42 mg/dL).^31,32
• Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; HDL-C< 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴ ●

CORRESPONDENCE

Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVD by ascertaining LDL-C

• The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL),estimation of LDL-C is invalid.
• The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC–HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴
• National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵
• Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

• Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴
• Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Continue to: Applying the estimate of 10-year ASCVD risk...

 

 

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

• Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

• Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention: Stratification by age

• 40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force (USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

• 20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴
• > 75 years, without ASCVD. In this group, the benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy...

 

 

Options for lipid-lowering pharmacotherapy

• Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

• Ezetimibe, a selective cholesterol-absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴
• PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23
• Inclisiran, an injectable small-interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴
• Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28
• Bempedoic acid is a small-molecule inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-intolerant patients, bempedoicacid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰
• Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL)and TG (42 mg/dL).^31,32
• Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; HDL-C< 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴ ●

CORRESPONDENCE

Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

Adding online mindfulness and self-compassion training to usual care may improve quality of life (QOL) in adults with atopic dermatitis (AD), according to results of a small randomized controlled trial in Japan.

“We found that skin disease–specific QOL improved over time with a large effect size,” lead study author Sanae Kishimoto, MHS, MPH, of the School of Public Health, Graduate School of Medicine at Kyoto University and colleagues write in JAMA Dermatology. “These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD.”
 

A bothersome disease that worsens quality of life

AD, a chronic, relapsing, inflammatory, multifactorial skin disease involving intense itching, affects an estimated 15%-30% of children and 2%-10% of adults, with the incidence increasing in industrialized countries, the authors state. 

d3sign/Getty Images

Measured by disability-adjusted life years, AD has the highest disease burden among skin diseases, and people with AD commonly have anxiety, depression, and sleep problems. Treatments include medications, other skin care, and lifestyle changes. New biologics appear to be effective but are expensive and need to be studied for their long-term safety, the authors add.

“Stress can make the skin worse, but at the same time the skin disease and symptoms cause stress,” Peter A. Lio, MD, who was not involved in the study, told this news organization by email. “This vicious cycle contributes greatly to impairing quality of life.”
 

A program focused on wise, kind self-care

In the SMiLE study, the authors recruited adults with moderate to severe AD and Dermatology Life Quality Index (DLQI) score above 6 from dermatology clinics and through online announcements over 1 year beginning in July 2019.

Participants averaged 36.3 years of age, 80% were women, and their mean AD duration was 26.6 years. Everyone was allowed to receive usual care during the study, except for dupilumab (a newly marketed drug when the study started), psychotherapy, or other mindfulness training.

The researchers randomly assigned 56 adults to receive mindfulness training in addition to their usual care and 51 to the wait list plus usual care. Those in the training group received eight weekly 90-minute online mindfulness and self-compassion sessions. Each group-based session was conducted at the same time and day of the week and included meditation, informal psychoeducation, inquiry, and a short lecture, along with an optional 1-day silent meditation retreat at week 7 and an optional 2-hour videoconferencing booster session at week 13.

The intervention encouraged a nonjudgmental relationship with stress using mindfulness-based stress reduction (MBSR) and emphasized a compassionate relationship with oneself during suffering using mindful self-compassion (MSC). The program was developed and taught by lead author Dr. Kishimoto, a Japanese licensed clinical psychologist who has a history of AD, the paper notes.

At 13 weeks, after completing electronic assessments, patients in the training group showed greater improvement in the DLQI score than those on the wait list (between-group difference estimate, –6.34; 95% confidence interval, –8.27 to –4.41; P < .001). The standardized effect size (Cohen’s d) at 13 weeks was –1.06 (95% CI, –1.39 to –0.74).

Patients in the training group also improved more in all secondary outcomes: severity, itch- and scratch-related visual analog scales, self-compassion, mindfulness, psychological symptoms, and adherence to dermatologist-advised treatments.

They were also more likely to follow their dermatologist’s medical treatment plans, including moisturizer and topical steroid use.

One serious adverse event, endometrial cancer in one patient, was judged to be unrelated to the intervention.
 

Online format may give more patients access to treatment

“With relatively limited data in the literature, this particularly well-done, important study is likely to positively shape thinking around this topic,” said Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago. “This study nicely demonstrates that an online approach can be effective.

“In theory, these methods or techniques could democratize treatments like this, and open them up to many more patients,” he added. He would like to see partially or entirely automated apps (free of cost), similar to meditation “apps,” to treat patients more cost-effectively.

Dr. Lio explained that excluding participants on dupilumab (Dupixent) makes the results slightly less generalizable to patients with moderate to severe AD, who may have the most serious QOL challenges and who are often candidates for dupilumab.

“However, given that we almost never have all the known variables for a study, we are generally comfortable extrapolating that the intervention would likely be helpful for patients taking dupilumab as well, despite it not being specifically evaluated in that group,” he said.

Susan Massick, MD, of the department of dermatology at the Ohio State University Wexner Medical Center in Columbus, advises clinicians to take a multipronged approach to treating the physical and behavioral components of AD and to embrace therapies beyond prescription medications.

“Self-compassion training is another tool in our toolbox toward finding the right fix for our patients,” Dr. Massick said by email. She was not involved with this research.

“I applaud the focus of this study on behavioral health training as a means toward wellness and improved mindfulness,” she added. “I was impressed by the extent to which these simple measures helped improve the quality of life for patients who used the training.”

U.S. patients can benefit from these findings

“My sense is that AD patients the world over have many similar characteristics and concerns, so I would anticipate that the results would be comparable in a U.S. population,” Dr. Lio said. “Other studies performed in the U.S. also support this line of thinking.”

Although the study involved highly motivated patients in Japan, the suffering that patients with AD experience is universal regardless of race or ethnicity, Dr. Massick said. “Americans may be even more willing to embrace mindfulness and self-compassion training as a path toward better health and wellness.”

The study was funded by the Japan Agency for Medical Research and Development and the Mental Health Okamoto Memorial Foundation, the KDDI Foundation, the Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science.

Dr. Kishimoto and several coauthors report relevant financial relationships with pharmaceutical companies. Dr. Lio reports financial relationships with Sanofi and Regeneron, the joint developers of dupilumab. Dr. Massick reports no relevant financial relationships.

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

Adding online mindfulness and self-compassion training to usual care may improve quality of life (QOL) in adults with atopic dermatitis (AD), according to results of a small randomized controlled trial in Japan.

“We found that skin disease–specific QOL improved over time with a large effect size,” lead study author Sanae Kishimoto, MHS, MPH, of the School of Public Health, Graduate School of Medicine at Kyoto University and colleagues write in JAMA Dermatology. “These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD.”
 

A bothersome disease that worsens quality of life

AD, a chronic, relapsing, inflammatory, multifactorial skin disease involving intense itching, affects an estimated 15%-30% of children and 2%-10% of adults, with the incidence increasing in industrialized countries, the authors state. 

d3sign/Getty Images

Measured by disability-adjusted life years, AD has the highest disease burden among skin diseases, and people with AD commonly have anxiety, depression, and sleep problems. Treatments include medications, other skin care, and lifestyle changes. New biologics appear to be effective but are expensive and need to be studied for their long-term safety, the authors add.

“Stress can make the skin worse, but at the same time the skin disease and symptoms cause stress,” Peter A. Lio, MD, who was not involved in the study, told this news organization by email. “This vicious cycle contributes greatly to impairing quality of life.”
 

A program focused on wise, kind self-care

In the SMiLE study, the authors recruited adults with moderate to severe AD and Dermatology Life Quality Index (DLQI) score above 6 from dermatology clinics and through online announcements over 1 year beginning in July 2019.

Participants averaged 36.3 years of age, 80% were women, and their mean AD duration was 26.6 years. Everyone was allowed to receive usual care during the study, except for dupilumab (a newly marketed drug when the study started), psychotherapy, or other mindfulness training.

The researchers randomly assigned 56 adults to receive mindfulness training in addition to their usual care and 51 to the wait list plus usual care. Those in the training group received eight weekly 90-minute online mindfulness and self-compassion sessions. Each group-based session was conducted at the same time and day of the week and included meditation, informal psychoeducation, inquiry, and a short lecture, along with an optional 1-day silent meditation retreat at week 7 and an optional 2-hour videoconferencing booster session at week 13.

The intervention encouraged a nonjudgmental relationship with stress using mindfulness-based stress reduction (MBSR) and emphasized a compassionate relationship with oneself during suffering using mindful self-compassion (MSC). The program was developed and taught by lead author Dr. Kishimoto, a Japanese licensed clinical psychologist who has a history of AD, the paper notes.

At 13 weeks, after completing electronic assessments, patients in the training group showed greater improvement in the DLQI score than those on the wait list (between-group difference estimate, –6.34; 95% confidence interval, –8.27 to –4.41; P < .001). The standardized effect size (Cohen’s d) at 13 weeks was –1.06 (95% CI, –1.39 to –0.74).

Patients in the training group also improved more in all secondary outcomes: severity, itch- and scratch-related visual analog scales, self-compassion, mindfulness, psychological symptoms, and adherence to dermatologist-advised treatments.

They were also more likely to follow their dermatologist’s medical treatment plans, including moisturizer and topical steroid use.

One serious adverse event, endometrial cancer in one patient, was judged to be unrelated to the intervention.
 

Online format may give more patients access to treatment

“With relatively limited data in the literature, this particularly well-done, important study is likely to positively shape thinking around this topic,” said Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago. “This study nicely demonstrates that an online approach can be effective.

“In theory, these methods or techniques could democratize treatments like this, and open them up to many more patients,” he added. He would like to see partially or entirely automated apps (free of cost), similar to meditation “apps,” to treat patients more cost-effectively.

Dr. Lio explained that excluding participants on dupilumab (Dupixent) makes the results slightly less generalizable to patients with moderate to severe AD, who may have the most serious QOL challenges and who are often candidates for dupilumab.

“However, given that we almost never have all the known variables for a study, we are generally comfortable extrapolating that the intervention would likely be helpful for patients taking dupilumab as well, despite it not being specifically evaluated in that group,” he said.

Susan Massick, MD, of the department of dermatology at the Ohio State University Wexner Medical Center in Columbus, advises clinicians to take a multipronged approach to treating the physical and behavioral components of AD and to embrace therapies beyond prescription medications.

“Self-compassion training is another tool in our toolbox toward finding the right fix for our patients,” Dr. Massick said by email. She was not involved with this research.

“I applaud the focus of this study on behavioral health training as a means toward wellness and improved mindfulness,” she added. “I was impressed by the extent to which these simple measures helped improve the quality of life for patients who used the training.”

U.S. patients can benefit from these findings

“My sense is that AD patients the world over have many similar characteristics and concerns, so I would anticipate that the results would be comparable in a U.S. population,” Dr. Lio said. “Other studies performed in the U.S. also support this line of thinking.”

Although the study involved highly motivated patients in Japan, the suffering that patients with AD experience is universal regardless of race or ethnicity, Dr. Massick said. “Americans may be even more willing to embrace mindfulness and self-compassion training as a path toward better health and wellness.”

The study was funded by the Japan Agency for Medical Research and Development and the Mental Health Okamoto Memorial Foundation, the KDDI Foundation, the Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science.

Dr. Kishimoto and several coauthors report relevant financial relationships with pharmaceutical companies. Dr. Lio reports financial relationships with Sanofi and Regeneron, the joint developers of dupilumab. Dr. Massick reports no relevant financial relationships.

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

Adding online mindfulness and self-compassion training to usual care may improve quality of life (QOL) in adults with atopic dermatitis (AD), according to results of a small randomized controlled trial in Japan.

“We found that skin disease–specific QOL improved over time with a large effect size,” lead study author Sanae Kishimoto, MHS, MPH, of the School of Public Health, Graduate School of Medicine at Kyoto University and colleagues write in JAMA Dermatology. “These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD.”
 

A bothersome disease that worsens quality of life

AD, a chronic, relapsing, inflammatory, multifactorial skin disease involving intense itching, affects an estimated 15%-30% of children and 2%-10% of adults, with the incidence increasing in industrialized countries, the authors state. 

d3sign/Getty Images

Measured by disability-adjusted life years, AD has the highest disease burden among skin diseases, and people with AD commonly have anxiety, depression, and sleep problems. Treatments include medications, other skin care, and lifestyle changes. New biologics appear to be effective but are expensive and need to be studied for their long-term safety, the authors add.

“Stress can make the skin worse, but at the same time the skin disease and symptoms cause stress,” Peter A. Lio, MD, who was not involved in the study, told this news organization by email. “This vicious cycle contributes greatly to impairing quality of life.”
 

A program focused on wise, kind self-care

In the SMiLE study, the authors recruited adults with moderate to severe AD and Dermatology Life Quality Index (DLQI) score above 6 from dermatology clinics and through online announcements over 1 year beginning in July 2019.

Participants averaged 36.3 years of age, 80% were women, and their mean AD duration was 26.6 years. Everyone was allowed to receive usual care during the study, except for dupilumab (a newly marketed drug when the study started), psychotherapy, or other mindfulness training.

The researchers randomly assigned 56 adults to receive mindfulness training in addition to their usual care and 51 to the wait list plus usual care. Those in the training group received eight weekly 90-minute online mindfulness and self-compassion sessions. Each group-based session was conducted at the same time and day of the week and included meditation, informal psychoeducation, inquiry, and a short lecture, along with an optional 1-day silent meditation retreat at week 7 and an optional 2-hour videoconferencing booster session at week 13.

The intervention encouraged a nonjudgmental relationship with stress using mindfulness-based stress reduction (MBSR) and emphasized a compassionate relationship with oneself during suffering using mindful self-compassion (MSC). The program was developed and taught by lead author Dr. Kishimoto, a Japanese licensed clinical psychologist who has a history of AD, the paper notes.

At 13 weeks, after completing electronic assessments, patients in the training group showed greater improvement in the DLQI score than those on the wait list (between-group difference estimate, –6.34; 95% confidence interval, –8.27 to –4.41; P < .001). The standardized effect size (Cohen’s d) at 13 weeks was –1.06 (95% CI, –1.39 to –0.74).

Patients in the training group also improved more in all secondary outcomes: severity, itch- and scratch-related visual analog scales, self-compassion, mindfulness, psychological symptoms, and adherence to dermatologist-advised treatments.

They were also more likely to follow their dermatologist’s medical treatment plans, including moisturizer and topical steroid use.

One serious adverse event, endometrial cancer in one patient, was judged to be unrelated to the intervention.
 

Online format may give more patients access to treatment

“With relatively limited data in the literature, this particularly well-done, important study is likely to positively shape thinking around this topic,” said Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago. “This study nicely demonstrates that an online approach can be effective.

“In theory, these methods or techniques could democratize treatments like this, and open them up to many more patients,” he added. He would like to see partially or entirely automated apps (free of cost), similar to meditation “apps,” to treat patients more cost-effectively.

Dr. Lio explained that excluding participants on dupilumab (Dupixent) makes the results slightly less generalizable to patients with moderate to severe AD, who may have the most serious QOL challenges and who are often candidates for dupilumab.

“However, given that we almost never have all the known variables for a study, we are generally comfortable extrapolating that the intervention would likely be helpful for patients taking dupilumab as well, despite it not being specifically evaluated in that group,” he said.

Susan Massick, MD, of the department of dermatology at the Ohio State University Wexner Medical Center in Columbus, advises clinicians to take a multipronged approach to treating the physical and behavioral components of AD and to embrace therapies beyond prescription medications.

“Self-compassion training is another tool in our toolbox toward finding the right fix for our patients,” Dr. Massick said by email. She was not involved with this research.

“I applaud the focus of this study on behavioral health training as a means toward wellness and improved mindfulness,” she added. “I was impressed by the extent to which these simple measures helped improve the quality of life for patients who used the training.”

U.S. patients can benefit from these findings

“My sense is that AD patients the world over have many similar characteristics and concerns, so I would anticipate that the results would be comparable in a U.S. population,” Dr. Lio said. “Other studies performed in the U.S. also support this line of thinking.”

Although the study involved highly motivated patients in Japan, the suffering that patients with AD experience is universal regardless of race or ethnicity, Dr. Massick said. “Americans may be even more willing to embrace mindfulness and self-compassion training as a path toward better health and wellness.”

The study was funded by the Japan Agency for Medical Research and Development and the Mental Health Okamoto Memorial Foundation, the KDDI Foundation, the Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science.

Dr. Kishimoto and several coauthors report relevant financial relationships with pharmaceutical companies. Dr. Lio reports financial relationships with Sanofi and Regeneron, the joint developers of dupilumab. Dr. Massick reports no relevant financial relationships.

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

BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.

The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.

“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
 

Improving health by tackling legal barriers

Health-harming legal needs – social determinants of health that have a legal remedy – are drivers of poor health outcomes, particularly for Black women and children, Ms. Richardson said.

The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.

Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.

From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.

The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.

Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.

Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
 

COVID ... or morning sickness?

In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.

With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.

Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.

“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”

Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.

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

BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.

The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.

“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
 

Improving health by tackling legal barriers

Health-harming legal needs – social determinants of health that have a legal remedy – are drivers of poor health outcomes, particularly for Black women and children, Ms. Richardson said.

The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.

Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.

From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.

The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.

Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.

Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
 

COVID ... or morning sickness?

In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.

With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.

Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.

“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”

Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.

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

BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.

The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.

“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
 

Improving health by tackling legal barriers

Health-harming legal needs – social determinants of health that have a legal remedy – are drivers of poor health outcomes, particularly for Black women and children, Ms. Richardson said.

The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.

Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.

From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.

The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.

Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.

Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
 

COVID ... or morning sickness?

In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.

With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.

Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.

“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”

Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.

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

Doctors or AI? Lukewarm vote of confidence goes to …

Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.

Alexandra_Koch/Pixabay

And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.

They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?

And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.

How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
 

Explaining the joke makes it funnier, right?

Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”

Amy/Pixabay

This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.

Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.

In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.

During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.

The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
 

Hot take: Humans aren’t that special

We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.

jacoblund/iStock/Getty Images

Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.

This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.

“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.

The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.

Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.

So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.

Doctors or AI? Lukewarm vote of confidence goes to …

Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.

Alexandra_Koch/Pixabay

And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.

They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?

And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.

How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
 

Explaining the joke makes it funnier, right?

Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”

Amy/Pixabay

This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.

Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.

In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.

During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.

The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
 

Hot take: Humans aren’t that special

We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.

jacoblund/iStock/Getty Images

Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.

This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.

“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.

The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.

Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.

So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.

Doctors or AI? Lukewarm vote of confidence goes to …

Well, we’ve got some good news for the physicians out there, and we’ve got some bad news. Which do you want first? Okay, we’re mostly hearing good news, so here goes: Most people would choose a human doctor over artificial intelligence for the diagnosis and treatment of their medical conditions.

Alexandra_Koch/Pixabay

And the bad news? In the survey we’re talking about, “most” was 53%, so not exactly a huge victory for the carbon-based life forms. Yup, about 47% of the 2,472 respondents said they would prefer an AI-based clinic over a human specialist, and that number went up if individuals were told that their primary care physicians were on board with AI, “or otherwise nudged to consider AI as good,” the research team said in a written statement released by the University of Arizona, Tucson.

They went on to add that “this signaled the significance of the human physician in guiding a patient’s decision.” So patients will still need their doctors in the future to … um … this is a bit awkward … tell them how good the AI is?

And yes, we know that ChatGPT is already doing the same thing to journalists, but could it write a medical-humor column? Not a chance. Probably can’t even tell a joke.

How do ghosts get rid of wrinkles? Boo-tox. There, let’s see ChatGPT do that.
 

Explaining the joke makes it funnier, right?

Here at LOTME headquarters, we live by one simple rule, passed down directly from the Buddha himself: “Never let a good presurgical assessment of refractory epilepsy go to waste. Also, don’t believe everything you read on the Internet.”

Amy/Pixabay

This human-created joke has been brought to you by the leading theory of humor, which states that comedy stems from our brain reacting to an incongruous part of reality in a positive way. These positive emotions light up our neurons in a specific fashion, and boom, comedy is achieved.

Previous studies into the science of comedy have typically used functional MRI to analyze the brain while it was gripped in the throes of a comedic reaction. Unfortunately, fMRI cannot detect the entirety of the electromagnetic spectrum generated by the brain during these moments, so observing scientists have been, quite literally, missing out on some of the joke. And that’s where a new study from France comes in.

In the study, the researchers showed a group of patients with epilepsy who were hooked up to deep brain electrodes and a high-tech neuroimaging machine – part of the aforementioned presurgical assessment – a 3-minute excerpt from a Charlie Chaplin movie and analyzed their brain activity. Why Charlie Chaplin? Simple. Slapstick is perhaps the most accessible form of comedy across cultures. We can all appreciate a man getting hit in the head with a coconut. The world’s oldest bar joke or whatever this is? Not so much.

During the funniest scenes, all study participants showed increased high-frequency gamma waves (indicating high cognitive engagement) and a decrease in low-frequency waves (indicating reduced inattention and introspection). During unfunny scenes, such as transition moments, the opposite occurred. Importantly, this inverse relationship occurred in the temporal lobe but not in other regions, supporting previous research that indicated humor was mainly processed in the temporal lobe.

The investigators suggested future research should focus on longer videos with more complex forms of comedy, such as jokes, irony, sarcasm, or reference humor. So, uh, a guy getting hit in the head with two coconuts? That’s high-brow stuff right there.
 

Hot take: Humans aren’t that special

We humans have always prided ourselves on being different from “the animals” in an exceptional way. News flash! We aren’t. We may be the apex predator, but new research shows that humans, as part of the animal kingdom, just aren’t special.

jacoblund/iStock/Getty Images

Not special? How can they say that? Are gorillas doing open-heart surgery? Do wolverines tell jokes? At a more basic level, though, the way we operate as mammals in societies is not unique or even new. Elephants are known to mourn their deceased and to have funeral-like practices, ants invented agriculture, and we’re certainly not the only species that has figured out how to use tools.

This new research just demonstrates another way we aren’t exceptional, and that’s in our mating practices and outcomes.

“Humans appear to resemble mammals that live in monogamous partnerships and to some extent, those classified as cooperative breeders, where breeding individuals have to rely on the help of others to raise their offspring,” Monique Borgerhoff Mulder, PhD, professor emerita of anthropology at the University of California, Davis, said in a written statement.

The research team, which consisted of over 100 investigators, looked at 90 human populations based on data from over 80,000 people globally and compared the human data with 49 different nonhuman mammal species. In polygynous societies in which men take several wives, they found, women have more access to resources like food, shelter, and parenting help. Monogamy, on the other hand, “can drive significant inequalities among women,” Dr. Borgerhoff Mulder said, by promoting large differences in the number of children couples produce.

Human day-to-day behavior and child-rearing habits – one parent taking a daughter to ballet class and fixing dinner so the other parent can get to exercise class before picking up the son from soccer practice – may have us thinking that we are part of an evolved society, but really we are not much different than other mammals that hunt, forage for food, and rear and teach their children, the researchers suggested.

So, yes, humans can travel to the moon, create a vaccine for smallpox, and hit other humans with coconuts, but when it comes to simply having offspring or raising them, we’re not all that special. Get over it.

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

For health professionals, the thought that our parents and grandparents don’t have sex – or didn’t – might be comforting.

The reality is that, for a significant proportion of our older patients, sex has no use-by date. Humans are sexual beings throughout their lives, yet the culture has concealed that fact.

According to Rome, the purpose of sex is to make children. According to Hollywood, sex is only for the young, the healthy, and the beautiful. For the medical profession, sex consists mainly of risks or dysfunctions.

The results of these biases? Many middle-aged people fear their later sexual life. And medical professionals rarely ask about sexuality. That failing can be harmful. Sexuality and intimacy are essential elements for quality of life, with clear physical, emotional, and relational benefits.

Let’s look at the data when researchers dared to ask seniors about their sexuality.

We start with the 2015 U.K. national research on sexuality. The study found a link between age and a decline in various aspects of sexual activity – but not a zeroing-out. For example, among men aged 70-79, 59% reported having had sex in the past year, with 19% having intercourse at least twice a month and 18% masturbating at least that often. Above age 80, those numbers dropped to 39%, 6%, and 5%, respectively. The reason behind the declines? A combination of taboo, fear of disease, use of medications or other interventions that disrupt sexual function or cause disfigurement, and a little bit of age itself.

What about women? Among women ages 70-79, 39% said they’d had sex in the past year, with 6% having intercourse at least twice per month and 5% masturbating two times or more monthly. Above age 80, those numbers were 10%, 4.5%, and 1%, respectively. Driving the falloff in women were the same factors as for men, plus the sad reality that many heterosexual women become widowed because their older male partners die earlier.

The male-female difference also reflects lower levels of testosterone in women. And, because women say they value intimacy more than performance, we have two explanations for their lower frequency of masturbation. After all, a lot of intimacy occurs without either intercourse or masturbation.

Surprising and relevant is the amount of distress – or rather, their relative lack thereof – older patients report because of sexual problems. At age 18-44, 11% of U.S. women indicated sexual distress; at age 45-64, the figure was 15%; and at age 65 and up, 9%.

For clinicians, those figures should prompt us to look more closely at alternative forms of sexual expression – those not involving intercourse or masturbation – in the aged, a field physicians typically do not consider.

Although dyspareunia or erectile problems affect many in long-standing relationships, neither is a reason to abstain from sexual pleasure. Indeed, in many couples, oral sex will replace vaginal intercourse, and if urinary, fecal, or flatal incontinence intrude, couples often waive oral sex in favor of more cuddling, kissing, digital stimulation, and other forms of sexual pleasure.
 

What about the expiry date for sex?

Fascinating research from Nils Beckman, PhD, and colleagues found that the sex drive persists even as people (and men in particular) reach their 100th year. Dr. Beckman’s group interviewed 269 Swedish seniors, all without dementia, at age 97. Sexual desire was affirmed by 27% of men and 5% of women in the survey. Among the men, 32% said they still had sexual thoughts, compared with 18% of women. Meanwhile, 26% of the men and 15% of the women said they missed sexual activity.

What should clinicians do with this information? First, we could start talking about sex with our older patients. According to the 97-year-old Swedes, most want us to! More than 8 in 10 of both women and men in the survey expressed positive views about questions on sexuality. And please don’t be scared to address the subject in the single senior. They, too, can have a sexual or relationship issue and are happy when we raise the subject. They’re not scared to talk about masturbation, either.

When caring for those with chronic diseases, cancer, in the course of physical rehabilitation, and even in the last phase of life, the clinical experience indicates that our patients are happy when we address sexuality and intimacy. Doing so can open the door to the admission of a problem and a corresponding solution, a lubricant or a PDE5 inhibitor.

But sometimes the solution is the conversation itself: Roughly 25% of patients are sufficiently helped simply by talking about sex. Addressing the importance of sexual pleasure is nearly always valuable.

Here are a few ice-breakers I find helpful:

• Did taking this medication change aspects of sexuality? If so, does that bother you?
• Knowing that continuing intimacy is healthy, do you mind if I address that subject?
• We know that aspects of sexuality and intimacy are healthy. Without a partner, some people become sexually isolated. Would you like to talk about that?’

If addressing sexuality has benefits, what about sex itself?

We are gradually learning more about the many short-, intermediate-, and long-term health benefits of solo and joint sexual activity. Short-term benefits include muscle relaxation, pain relief (even, perhaps ironically, for headaches), and better sleep – all pretty valuable for older adults. Examples of intermediate-term benefits include stress relief and less depression. Research from the United States has found that hugging can reduce the concentrations of proinflammatory cytokines, and kissing positively influences cholesterol levels.

Finally, while the long-term benefits of sex might be less relevant for seniors, they do exist.

Among them are delayed onset of dementia and a substantial reduction in cardiovascular and cerebrovascular problems in men. More sex has been linked to longevity, with men benefiting a bit more than women from going through the entire process, including an orgasm, whereas women appear to gain from having a “satisfying” sex life, which does not always require an orgasm.

Let us not forget that these benefits apply to both patients and clinicians alike. Addressing intimacy and sexuality can ease eventual sexual concerns and potentially create a stronger clinician-patient relationship.

Dr. Gianotten, MD is emeritus senior lecturer in medical sexology, Erasmus University Medical Centre, Rotterdam, the Netherlands. He reported no conflicts of interest.

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

For health professionals, the thought that our parents and grandparents don’t have sex – or didn’t – might be comforting.

The reality is that, for a significant proportion of our older patients, sex has no use-by date. Humans are sexual beings throughout their lives, yet the culture has concealed that fact.

According to Rome, the purpose of sex is to make children. According to Hollywood, sex is only for the young, the healthy, and the beautiful. For the medical profession, sex consists mainly of risks or dysfunctions.

The results of these biases? Many middle-aged people fear their later sexual life. And medical professionals rarely ask about sexuality. That failing can be harmful. Sexuality and intimacy are essential elements for quality of life, with clear physical, emotional, and relational benefits.

Let’s look at the data when researchers dared to ask seniors about their sexuality.

We start with the 2015 U.K. national research on sexuality. The study found a link between age and a decline in various aspects of sexual activity – but not a zeroing-out. For example, among men aged 70-79, 59% reported having had sex in the past year, with 19% having intercourse at least twice a month and 18% masturbating at least that often. Above age 80, those numbers dropped to 39%, 6%, and 5%, respectively. The reason behind the declines? A combination of taboo, fear of disease, use of medications or other interventions that disrupt sexual function or cause disfigurement, and a little bit of age itself.

What about women? Among women ages 70-79, 39% said they’d had sex in the past year, with 6% having intercourse at least twice per month and 5% masturbating two times or more monthly. Above age 80, those numbers were 10%, 4.5%, and 1%, respectively. Driving the falloff in women were the same factors as for men, plus the sad reality that many heterosexual women become widowed because their older male partners die earlier.

The male-female difference also reflects lower levels of testosterone in women. And, because women say they value intimacy more than performance, we have two explanations for their lower frequency of masturbation. After all, a lot of intimacy occurs without either intercourse or masturbation.

Surprising and relevant is the amount of distress – or rather, their relative lack thereof – older patients report because of sexual problems. At age 18-44, 11% of U.S. women indicated sexual distress; at age 45-64, the figure was 15%; and at age 65 and up, 9%.

For clinicians, those figures should prompt us to look more closely at alternative forms of sexual expression – those not involving intercourse or masturbation – in the aged, a field physicians typically do not consider.

Although dyspareunia or erectile problems affect many in long-standing relationships, neither is a reason to abstain from sexual pleasure. Indeed, in many couples, oral sex will replace vaginal intercourse, and if urinary, fecal, or flatal incontinence intrude, couples often waive oral sex in favor of more cuddling, kissing, digital stimulation, and other forms of sexual pleasure.
 

What about the expiry date for sex?

Fascinating research from Nils Beckman, PhD, and colleagues found that the sex drive persists even as people (and men in particular) reach their 100th year. Dr. Beckman’s group interviewed 269 Swedish seniors, all without dementia, at age 97. Sexual desire was affirmed by 27% of men and 5% of women in the survey. Among the men, 32% said they still had sexual thoughts, compared with 18% of women. Meanwhile, 26% of the men and 15% of the women said they missed sexual activity.

What should clinicians do with this information? First, we could start talking about sex with our older patients. According to the 97-year-old Swedes, most want us to! More than 8 in 10 of both women and men in the survey expressed positive views about questions on sexuality. And please don’t be scared to address the subject in the single senior. They, too, can have a sexual or relationship issue and are happy when we raise the subject. They’re not scared to talk about masturbation, either.

When caring for those with chronic diseases, cancer, in the course of physical rehabilitation, and even in the last phase of life, the clinical experience indicates that our patients are happy when we address sexuality and intimacy. Doing so can open the door to the admission of a problem and a corresponding solution, a lubricant or a PDE5 inhibitor.

But sometimes the solution is the conversation itself: Roughly 25% of patients are sufficiently helped simply by talking about sex. Addressing the importance of sexual pleasure is nearly always valuable.

Here are a few ice-breakers I find helpful:

• Did taking this medication change aspects of sexuality? If so, does that bother you?
• Knowing that continuing intimacy is healthy, do you mind if I address that subject?
• We know that aspects of sexuality and intimacy are healthy. Without a partner, some people become sexually isolated. Would you like to talk about that?’

If addressing sexuality has benefits, what about sex itself?

We are gradually learning more about the many short-, intermediate-, and long-term health benefits of solo and joint sexual activity. Short-term benefits include muscle relaxation, pain relief (even, perhaps ironically, for headaches), and better sleep – all pretty valuable for older adults. Examples of intermediate-term benefits include stress relief and less depression. Research from the United States has found that hugging can reduce the concentrations of proinflammatory cytokines, and kissing positively influences cholesterol levels.

Finally, while the long-term benefits of sex might be less relevant for seniors, they do exist.

Among them are delayed onset of dementia and a substantial reduction in cardiovascular and cerebrovascular problems in men. More sex has been linked to longevity, with men benefiting a bit more than women from going through the entire process, including an orgasm, whereas women appear to gain from having a “satisfying” sex life, which does not always require an orgasm.

Let us not forget that these benefits apply to both patients and clinicians alike. Addressing intimacy and sexuality can ease eventual sexual concerns and potentially create a stronger clinician-patient relationship.

Dr. Gianotten, MD is emeritus senior lecturer in medical sexology, Erasmus University Medical Centre, Rotterdam, the Netherlands. He reported no conflicts of interest.

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

For health professionals, the thought that our parents and grandparents don’t have sex – or didn’t – might be comforting.

The reality is that, for a significant proportion of our older patients, sex has no use-by date. Humans are sexual beings throughout their lives, yet the culture has concealed that fact.

According to Rome, the purpose of sex is to make children. According to Hollywood, sex is only for the young, the healthy, and the beautiful. For the medical profession, sex consists mainly of risks or dysfunctions.

The results of these biases? Many middle-aged people fear their later sexual life. And medical professionals rarely ask about sexuality. That failing can be harmful. Sexuality and intimacy are essential elements for quality of life, with clear physical, emotional, and relational benefits.

Let’s look at the data when researchers dared to ask seniors about their sexuality.

We start with the 2015 U.K. national research on sexuality. The study found a link between age and a decline in various aspects of sexual activity – but not a zeroing-out. For example, among men aged 70-79, 59% reported having had sex in the past year, with 19% having intercourse at least twice a month and 18% masturbating at least that often. Above age 80, those numbers dropped to 39%, 6%, and 5%, respectively. The reason behind the declines? A combination of taboo, fear of disease, use of medications or other interventions that disrupt sexual function or cause disfigurement, and a little bit of age itself.

What about women? Among women ages 70-79, 39% said they’d had sex in the past year, with 6% having intercourse at least twice per month and 5% masturbating two times or more monthly. Above age 80, those numbers were 10%, 4.5%, and 1%, respectively. Driving the falloff in women were the same factors as for men, plus the sad reality that many heterosexual women become widowed because their older male partners die earlier.

The male-female difference also reflects lower levels of testosterone in women. And, because women say they value intimacy more than performance, we have two explanations for their lower frequency of masturbation. After all, a lot of intimacy occurs without either intercourse or masturbation.

Surprising and relevant is the amount of distress – or rather, their relative lack thereof – older patients report because of sexual problems. At age 18-44, 11% of U.S. women indicated sexual distress; at age 45-64, the figure was 15%; and at age 65 and up, 9%.

For clinicians, those figures should prompt us to look more closely at alternative forms of sexual expression – those not involving intercourse or masturbation – in the aged, a field physicians typically do not consider.

Although dyspareunia or erectile problems affect many in long-standing relationships, neither is a reason to abstain from sexual pleasure. Indeed, in many couples, oral sex will replace vaginal intercourse, and if urinary, fecal, or flatal incontinence intrude, couples often waive oral sex in favor of more cuddling, kissing, digital stimulation, and other forms of sexual pleasure.
 

What about the expiry date for sex?

Fascinating research from Nils Beckman, PhD, and colleagues found that the sex drive persists even as people (and men in particular) reach their 100th year. Dr. Beckman’s group interviewed 269 Swedish seniors, all without dementia, at age 97. Sexual desire was affirmed by 27% of men and 5% of women in the survey. Among the men, 32% said they still had sexual thoughts, compared with 18% of women. Meanwhile, 26% of the men and 15% of the women said they missed sexual activity.

What should clinicians do with this information? First, we could start talking about sex with our older patients. According to the 97-year-old Swedes, most want us to! More than 8 in 10 of both women and men in the survey expressed positive views about questions on sexuality. And please don’t be scared to address the subject in the single senior. They, too, can have a sexual or relationship issue and are happy when we raise the subject. They’re not scared to talk about masturbation, either.

When caring for those with chronic diseases, cancer, in the course of physical rehabilitation, and even in the last phase of life, the clinical experience indicates that our patients are happy when we address sexuality and intimacy. Doing so can open the door to the admission of a problem and a corresponding solution, a lubricant or a PDE5 inhibitor.

But sometimes the solution is the conversation itself: Roughly 25% of patients are sufficiently helped simply by talking about sex. Addressing the importance of sexual pleasure is nearly always valuable.

Here are a few ice-breakers I find helpful:

• Did taking this medication change aspects of sexuality? If so, does that bother you?
• Knowing that continuing intimacy is healthy, do you mind if I address that subject?
• We know that aspects of sexuality and intimacy are healthy. Without a partner, some people become sexually isolated. Would you like to talk about that?’

If addressing sexuality has benefits, what about sex itself?

We are gradually learning more about the many short-, intermediate-, and long-term health benefits of solo and joint sexual activity. Short-term benefits include muscle relaxation, pain relief (even, perhaps ironically, for headaches), and better sleep – all pretty valuable for older adults. Examples of intermediate-term benefits include stress relief and less depression. Research from the United States has found that hugging can reduce the concentrations of proinflammatory cytokines, and kissing positively influences cholesterol levels.

Finally, while the long-term benefits of sex might be less relevant for seniors, they do exist.

Among them are delayed onset of dementia and a substantial reduction in cardiovascular and cerebrovascular problems in men. More sex has been linked to longevity, with men benefiting a bit more than women from going through the entire process, including an orgasm, whereas women appear to gain from having a “satisfying” sex life, which does not always require an orgasm.

Let us not forget that these benefits apply to both patients and clinicians alike. Addressing intimacy and sexuality can ease eventual sexual concerns and potentially create a stronger clinician-patient relationship.

Dr. Gianotten, MD is emeritus senior lecturer in medical sexology, Erasmus University Medical Centre, Rotterdam, the Netherlands. He reported no conflicts of interest.

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