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Novel medication tied to better quality of life in major depression
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
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Bilateral palmar rash
A biopsy was performed and the pathology report showed ectatic, thin-walled vessels consistent with telangiectasias. There were no other inflammatory, infectious, or malignant changes.
Telangiectasias are caused by permanent dilatation of subpapillary plexus end vessels. Unlike petechiae and angiomata, telangiectasias blanch with pressure. They usually manifest as small, bright red, nonpulsatile vascular lesions with a fine, netlike pattern on the surface of the skin. Telangiectasis can affect many organs (eg, intestines, bladder, brain, eyes) and may occur in patients with certain genetic disorders and environmental exposures (eg, radiation).1
Palmar telangiectasias are specifically associated with hereditary hemorrhagic telangiectasia, dermatomyositis, Grave disease, CREST syndrome, systemic lupus erythematosus, and smoking.2 Sun exposure and smoking are the main risk factors for the development of telangiectasias.1
This patient had no history of autoimmune disease or hyperthyroidism, and no one in her family had telangiectasis. Thus, the likely cause of her lesions was smoking. While the pathophysiology is not fully understood, it is likely related to the vasoconstrictive quality of nicotine, causing ischemia in the dermis. This chronic, low-grade ischemia may trigger the compensatory development of telangiectasias.2
This patient was informed that her telangiectasias were most likely caused by her smoking and that the lesions themselves did not require treatment. She was encouraged to continue her smoking cessation efforts with her primary care provider.
Photos courtesy of Daniel Stulberg, MD. Text courtesy of Mia MJ Coleman, BA, BS, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
1. Schieving JH, Shoenaker MHD, Weemaes CM, et al. Telangiectasias: Small lesions referring to serious disorders. Eur J Paediatr Neurol. 2017;21:807-815. doi: 10.1016/j.ejpn.2017.07.016
2. Levi A, Shechter R, Lapidoth M, et al. Palmar telangiectasias: a cutaneous sign for smoking. Dermatology. 2017;233:390-395. doi: 10.1159/000481855
A biopsy was performed and the pathology report showed ectatic, thin-walled vessels consistent with telangiectasias. There were no other inflammatory, infectious, or malignant changes.
Telangiectasias are caused by permanent dilatation of subpapillary plexus end vessels. Unlike petechiae and angiomata, telangiectasias blanch with pressure. They usually manifest as small, bright red, nonpulsatile vascular lesions with a fine, netlike pattern on the surface of the skin. Telangiectasis can affect many organs (eg, intestines, bladder, brain, eyes) and may occur in patients with certain genetic disorders and environmental exposures (eg, radiation).1
Palmar telangiectasias are specifically associated with hereditary hemorrhagic telangiectasia, dermatomyositis, Grave disease, CREST syndrome, systemic lupus erythematosus, and smoking.2 Sun exposure and smoking are the main risk factors for the development of telangiectasias.1
This patient had no history of autoimmune disease or hyperthyroidism, and no one in her family had telangiectasis. Thus, the likely cause of her lesions was smoking. While the pathophysiology is not fully understood, it is likely related to the vasoconstrictive quality of nicotine, causing ischemia in the dermis. This chronic, low-grade ischemia may trigger the compensatory development of telangiectasias.2
This patient was informed that her telangiectasias were most likely caused by her smoking and that the lesions themselves did not require treatment. She was encouraged to continue her smoking cessation efforts with her primary care provider.
Photos courtesy of Daniel Stulberg, MD. Text courtesy of Mia MJ Coleman, BA, BS, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
A biopsy was performed and the pathology report showed ectatic, thin-walled vessels consistent with telangiectasias. There were no other inflammatory, infectious, or malignant changes.
Telangiectasias are caused by permanent dilatation of subpapillary plexus end vessels. Unlike petechiae and angiomata, telangiectasias blanch with pressure. They usually manifest as small, bright red, nonpulsatile vascular lesions with a fine, netlike pattern on the surface of the skin. Telangiectasis can affect many organs (eg, intestines, bladder, brain, eyes) and may occur in patients with certain genetic disorders and environmental exposures (eg, radiation).1
Palmar telangiectasias are specifically associated with hereditary hemorrhagic telangiectasia, dermatomyositis, Grave disease, CREST syndrome, systemic lupus erythematosus, and smoking.2 Sun exposure and smoking are the main risk factors for the development of telangiectasias.1
This patient had no history of autoimmune disease or hyperthyroidism, and no one in her family had telangiectasis. Thus, the likely cause of her lesions was smoking. While the pathophysiology is not fully understood, it is likely related to the vasoconstrictive quality of nicotine, causing ischemia in the dermis. This chronic, low-grade ischemia may trigger the compensatory development of telangiectasias.2
This patient was informed that her telangiectasias were most likely caused by her smoking and that the lesions themselves did not require treatment. She was encouraged to continue her smoking cessation efforts with her primary care provider.
Photos courtesy of Daniel Stulberg, MD. Text courtesy of Mia MJ Coleman, BA, BS, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
1. Schieving JH, Shoenaker MHD, Weemaes CM, et al. Telangiectasias: Small lesions referring to serious disorders. Eur J Paediatr Neurol. 2017;21:807-815. doi: 10.1016/j.ejpn.2017.07.016
2. Levi A, Shechter R, Lapidoth M, et al. Palmar telangiectasias: a cutaneous sign for smoking. Dermatology. 2017;233:390-395. doi: 10.1159/000481855
1. Schieving JH, Shoenaker MHD, Weemaes CM, et al. Telangiectasias: Small lesions referring to serious disorders. Eur J Paediatr Neurol. 2017;21:807-815. doi: 10.1016/j.ejpn.2017.07.016
2. Levi A, Shechter R, Lapidoth M, et al. Palmar telangiectasias: a cutaneous sign for smoking. Dermatology. 2017;233:390-395. doi: 10.1159/000481855
Why nurses are raging and quitting after the RaDonda Vaught verdict
Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.
Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.
Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.
Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.
“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”
In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. Ultimately, they say, it will worsen health care for all.
Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.
“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’
“Well, nobody is going to say that now.”
Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.
Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.
Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.
“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”
Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.
Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.
Some of Ms. Vaught’s peers support the conviction.
Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”
Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.
“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”
Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”
“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”
The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.
Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.
But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.
Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.
“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.
Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.
Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.
Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.
“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”
In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. Ultimately, they say, it will worsen health care for all.
Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.
“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’
“Well, nobody is going to say that now.”
Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.
Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.
Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.
“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”
Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.
Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.
Some of Ms. Vaught’s peers support the conviction.
Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”
Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.
“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”
Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”
“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”
The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.
Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.
But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.
Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.
“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Emma Moore felt cornered. At a community health clinic in Portland, Ore., the 29-year-old nurse practitioner said she felt overwhelmed and undertrained. Coronavirus patients flooded the clinic for 2 years, and Ms. Moore struggled to keep up.
Then the stakes became clear. On March 25, about 2,400 miles away in a Tennessee courtroom, former nurse RaDonda Vaught was convicted of two felonies and facing 8 years in prison for a fatal medication mistake.
Like many nurses, Ms. Moore wondered if that could be her. She’d made medication errors before, although none so grievous. But what about the next one? In the pressure cooker of pandemic-era health care, another mistake felt inevitable.
Four days after Ms. Vaught’s verdict, Ms. Moore quit. She said Ms. Vaught’s verdict contributed to her decision.
“It’s not worth the possibility or the likelihood that this will happen,” Ms. Moore said, “if I’m in a situation where I’m set up to fail.”
In the wake of Ms. Vaught’s trial – an extremely rare case of a health care worker being criminally prosecuted for a medical error – nurses and nursing organizations have condemned the verdict through tens of thousands of social media posts, shares, comments, and videos. Ultimately, they say, it will worsen health care for all.
Statements from the American Nurses Association, the American Association of Critical-Care Nurses, and the National Medical Association said Ms. Vaught’s conviction set a “dangerous precedent.” Linda H. Aiken, PhD, RN, a nursing and sociology professor at the University of Pennsylvania, Philadelphia, said that although Ms. Vaught’s case is an “outlier,” it will make nurses less forthcoming about mistakes.
“One thing that everybody agrees on is it’s going to have a dampening effect on the reporting of errors or near misses, which then has a detrimental effect on safety,” Dr. Aiken said. “The only way you can really learn about errors in these complicated systems is to have people say, ‘Oh, I almost gave the wrong drug because …’
“Well, nobody is going to say that now.”
Fear and outrage about Ms. Vaught’s case have swirled among nurses on Facebook, Twitter, and Reddit. On TikTok, a video platform increasingly popular among medical professionals, videos with the “#RaDondaVaught” hashtag totaled more than 47 million views.
Ms. Vaught’s supporters catapulted a plea for her clemency to the top of Change.org, a petition website. And thousands also joined a Facebook group planning to gather in protest outside Ms. Vaught’s sentencing hearing in May.
Ashley Bartholomew, BSN, RN, a 36-year-old Tampa nurse who followed the trial through YouTube and Twitter, echoed the fear of many others. Nurses have long felt forced into “impossible situations” by mounting responsibilities and staffing shortages, she said, particularly in hospitals that operate with lean staffing models.
“The big response we are seeing is because all of us are acutely aware of how bad the pandemic has exacerbated the existing problems,” Ms. Bartholomew said. And “setting a precedent for criminally charging [for] an error is only going to make this exponentially worse.”
Ms. Vaught, who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted in the death of Charlene Murphey, a 75-year-old patient who died from a drug mix-up in 2017. Ms. Murphey was prescribed a dose of a sedative, Versed, but Ms. Vaught accidentally withdrew a powerful paralyzer, vecuronium, from an automated medication-dispensing cabinet and administered it to the patient.
Prosecutors argued that Ms. Vaught overlooked many obvious signs she’d withdrawn the wrong drug and did not monitor Ms. Murphey after she was given a deadly dose. Ms. Vaught owned up to the error but said it was an honest mistake, not a crime.
Some of Ms. Vaught’s peers support the conviction.
Scott G. Shelp, BSN, RN, a California nurse with a small YouTube channel, posted a 26-minute self-described “unpopular opinion” that Ms. Vaught deserves to serve prison time. “We need to stick up for each other,” he said, “but we cannot defend the indefensible.”
Mr. Shelp said he would never make the same error as Ms. Vaught and “neither would any competent nurse.” Regarding concerns that the conviction would discourage nurses from disclosing errors, Mr. Shelp said “dishonest” nurses “should be weeded out” of the profession anyway.
“In any other circumstance, I can’t believe anyone – including nurses – would accept ‘I didn’t mean to’ as a serious defense,” Mr. Shelp said. “Punishment for a harmful act someone actually did is justice.”
Ms. Vaught was acquitted of reckless homicide but convicted of a lesser charge, criminally negligent homicide, and gross neglect of an impaired adult. As outrage spread across social media, the Nashville district attorney’s office defended the conviction, saying in a statement it was “not an indictment against the nursing profession or the medical community.”
“This case is, and always has been, about the one single individual who made 17 egregious actions, and inactions, that killed an elderly woman,” said the office’s spokesperson, Steve Hayslip. “The jury found that Vaught’s actions were so far below the protocols and standard level of care, that the jury (which included a longtime nurse and another health care professional) returned a guilty verdict in less than four hours.”
The office of Tennessee Gov. Bill Lee confirmed he is not considering clemency for Ms. Vaught despite the Change.org petition, which had amassed about 187,000 signatures as of April 4.
Casey Black, press secretary for Gov. Lee, said that outside of death penalty cases the governor relies on the Board of Parole to recommend defendants for clemency, which happens only after sentencing and a board investigation.
But the controversy around Ms. Vaught’s case is far from over. As of April 4, more than 8,200 people had joined a Facebook group planning a march in protest outside the courthouse during her sentencing May 13.
Among the event’s planners is Tina Visant, the host of “Good Nurse Bad Nurse,” a podcast that followed Ms. Vaught’s case and opposed her prosecution.
“I don’t know how Nashville is going to handle it,” Ms. Visant said of the protest during a recent episode about Ms. Vaught’s trial. “There are a lot of people coming from all over.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Novel tool could calculate CVD risk in T2DM
A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.
The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).
Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter
“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”
The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.
Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”
The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.
Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.
However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.
Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.
A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.
The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).
Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter
“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”
The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.
Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”
The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.
Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.
However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.
Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.
A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.
The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).
Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter
“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”
The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.
Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”
The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.
Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.
However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.
Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.
FROM HYPERTENSION
Brain implant is a potential life-changer for paralyzed patients
, results of a small, first-in-human study show.
A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.
“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.
The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.
“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Minimally invasive
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.
“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.
Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.
“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.
Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.
“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”
Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
No adverse events
Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.
“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”
The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.
The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.
A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.
Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.
Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.
“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
Greater independence
Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.
Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.
Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.
There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.
Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
Advancing the field
Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.
Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.
Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.
However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.
“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”
The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.
A version of this article first appeared on Medscape.com.
, results of a small, first-in-human study show.
A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.
“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.
The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.
“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Minimally invasive
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.
“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.
Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.
“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.
Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.
“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”
Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
No adverse events
Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.
“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”
The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.
The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.
A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.
Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.
Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.
“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
Greater independence
Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.
Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.
Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.
There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.
Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
Advancing the field
Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.
Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.
Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.
However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.
“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”
The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.
A version of this article first appeared on Medscape.com.
, results of a small, first-in-human study show.
A potential life changer for patients with amyotrophic lateral sclerosis (ALS), the minimally invasive device enables patients to carry out important activities of daily living.
“Our participants are able to use the device to perform tasks like sending email, texting loved ones and caregivers, browsing the web, and doing personal finances such as online banking,” study investigator Douglas J. Weber, PhD, professor of mechanical engineering and neuroscience, Carnegie Mellon University, Pittsburgh, told a press briefing.
The technology allowed one patient to write a book (due out later this year) and another patient to maintain communication despite losing his ability to speak, said the study’s lead investigator, Bruce Campbell, MBBS, PhD, professor of neurology, Royal Melbourne Hospital, University of Melbourne.
“In addition to providing patients with communicative capabilities not possible as a result of their disease, it is our goal to enable patients to be more independently involved in their care going forward, by enabling effective and faster communication directly with their caregiver and physician,” said Dr. Campbell.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Minimally invasive
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Patients with ALS eventually lose the ability to control muscle movement, often leading to total paralysis.
“Extending the period in which patients are able to communicate with loved ones and caregivers could provide a very meaningful benefit to patients with ALS,” said Dr. Weber.
Brain-computer interfaces measure and translate brain signals, with some functioning as motor neuro-prostheses. These devices provide direct communication between the brain and an external device by recording and decoding signals from the precentral gyrus as the result of movement intention.
“The technology has potential to empower the more than five million people in the U.S. who are severely paralyzed to once again perform important activities of daily living independently,” said Dr. Weber.
Until now, motor neuro-prostheses required surgery to remove a portion of the skull and place electrodes on to the brain. However, the new minimally invasive motor neuro-prostheses reach the brain by vascular access, dispensing with the need for a craniotomy.
“The brain-computer interface device used in our study is unique in that it does not require invasive open surgery to implant,” said Dr. Weber. “Instead this is an endovascular brain-computer interface.”
Using a catheter, surgeons feed the BCI through one of two jugular veins in the neck. They position an array of 16 sensors or electrodes on a stent-like scaffold that deploys against the walls of the superior sagittal sinus.
No adverse events
Describing the device, Dr. Weber said the electrodes or sensing elements are tiny and the body of the stent, which serves as a scaffold to support the electrodes, resembles a standard endovascular stent.
“It’s very small at the time of delivery because it’s held within the body of a catheter, but then when deployed it expands to contact the wall of the vein.”
The device transmits brain signals from the motor cortex to an electronics unit, located in a subcutaneous pocket that decodes movement signals. The machine-learning decoder is programmed as follows: When a trainer asked participants to attempt certain movements, like tapping their foot or extending their knee, the decoder analyzes nerve cell signals from those movement attempts. The decoder is able to translate movement signals into computer navigation.
The study included four patients with ALS who were paralyzed because of the disease and were trained to use the device.
A key safety endpoint was device-related serious adverse events resulting in death or increased disability during the post-implant evaluation period. Results showed all four participants successfully completed the 12-month follow-up with no serious adverse events.
Researchers also assessed target vessel patency and incidence of device migration at 3 and 12 months. Postoperative imaging showed that in all participants, the blood vessel that held the implanted device remained open and stayed in place.
Addressing the potential for blood clots, Dr. Weber said that so far there has been no sign of clotting or vascular occlusion.
“The device itself integrates well into the walls of the blood vessel over time,” he said. “Within the acute period after implantation, there’s time where the device is exposed to the blood stream, but once it becomes encapsulated and fully integrated into the blood vessel wall, the risks of thrombosis diminish.”
Greater independence
Researchers also recorded signal fidelity and stability over 12 months and use of the brain-computer interface to perform routine tasks. All participants learned to use the motor neuro-prostheses with eye tracking for computer use. Eye tracking technology helps a computer determine what a person is looking at.
Using the system, patients were able to complete tasks without help. These included text messaging and managing finances. “Since the device is fully implanted and easy for patients to use, they can use the technology independently and in their own home,” said Dr. Weber.
Although the study started with patients with ALS, those paralyzed from other causes, such as an upper spinal cord injury or brain-stem stroke could also benefit from this technology, Dr. Weber said. In addition, the technology could be expanded to broaden brain communication capabilities potentially to include robotic limbs, he said.
There’s even the potential to use this minimally invasive brain interface technology to deliver therapies like deep brain stimulation, which Dr. Weber noted is a growing field. “It’s [the] early days, but it’s a very exciting new direction for brain interface technology,” he said.
Researchers are now recruiting patients for the first U.S.-based feasibility trial of the device that will be funded by the NIH, said Dr. Weber. A limitation of the research was the study’s small size.
Advancing the field
Reached for a comment, Kevin C. Davis, an MD and PhD student in the department of biomedical engineering, University of Miami Miller School of Medicine, said this new work moves the field forward in an important way.
Dr. Davis and colleagues have shown the effectiveness of another technology used to overcome paralysis – a small portable system that facilitates hand grasp of a patient with a spinal cord injury. He reported on this DBS-based BCI system at the American Association of Neurological Surgeons (AANS) 2021 Annual Meeting.
Developing effective brain-computer interfaces, and motor neural prosthetics that avoid surgery, as the team did in this new study, is “worth exploring,” said Dr. Davis.
However, although the device used in this new study avoids cranial surgery, “sole vascular access may limit the device’s ability to reach other areas of the brain more suitable for upper-limb motor prosthetics,” he said.
“Determining how much function such a device could provide to individuals with locked-in syndrome or paralysis will be important in determining its viability as an eventual clinical tool for patients.”
The study was supported by Synchron, the maker of the device, the U.S. Defense Advanced Research Projects Agency, the Office of Naval Research, the National Health and Medical Research Council of Australia, the Australian Federal Government Foundation, and the Motor Neuron Disease Research Institute of Australia.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Researchers present cellular atlas of the human gut
New research sheds light on how different cell types behave across all intestinal regions and demonstrates variations in gene expression between these cells across three independent organ donors.
Research led by Joseph Burclaff, PhD, of the University of North Carolina at Chapel Hill, explained that the regional differences observed in the study “highlight the importance of regional selection when studying the gut.” Dr. Burclaff and colleagues, whose findings were published online in Cellular and Molecular Gastroenterology and Hepatology, wrote that they hope their “database serves as a resource to understand how drugs affect the intestinal epithelium and as guidance for future precision medicine approaches.”
In the study, Dr. Burclaff and colleagues performed single-cell transcriptomics that covered the duodenum, jejunum, ileum, as well as ascending, descending, and transverse colon from three independently processed organ donors. The donors varied in age, race, and body mass index.
The investigators evaluated 12,590 single epithelial cells for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. The focus of the analyses was on intrinsic cell properties and their capacity for response to extrinsic signals found along the gut axis.
The research group assigned cells to 25 epithelial lineage clusters. According to the researchers, multiple accepted intestinal cell markers did not specifically mark all intestinal stem cells. In addition, the investigators explained that lysozyme expression was not unique to Paneth cells, and these cells lacked expression of certain “expected niche factors.” In fact, the researchers demonstrated lysozyme’s insufficiency for marking human Paneth cells.
Bestrophin-4þ (BEST4þ) cells, which expressed neuropeptide Y, demonstrated maturational differences between the colon and small intestine, suggesting organ-specific maturation for tuft and BEST4+ cells. In addition, the data from Dr. Burclaff and colleagues suggest BEST4+ cells are engaged in “diverse roles within the intestinal epithelium, laying the groundwork for functional studies.”
The researchers noted that “tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors.” Specifically, the researchers found these cells exhibit genes believed to be important for taste signaling, monitoring intestinal content, and signaling the immune system.
Certain classes of cell junctions, hormones, mucins, and nutrient absorption genes demonstrated “unappreciated regional expression differences across lineages,” the researchers wrote. The investigators added that the differential expression of receptors as well as drug targets across lineages demonstrated “biological variation and the potential for variegated responses.”
The researchers noted that while the regional differences identified in their study show the importance of regional selection during gut investigations, several previous colonic single-cell RNA sequencing studies did not specify the sample region or explain “if pooled samples are from consistent regions.”
In the study, the investigators also assessed how drugs may affect the intestinal epithelium and why certain side effects associated with pharmacologic agents occur. The researchers identified 498 drugs approved by the Food and Drug Administration that had 232 primary gene targets expressed in the gut epithelial dataset.
In their analysis, the researchers found that carboxylesterase-2, which metabolizes the drug irinotecan into biologically active SN-38, is the highest expressed phase 1 metabolism gene in the small intestine. Phase 2 enzyme UGT1A1, which inactivates SN-38, features low gut epithelial expression. The researchers explained that this finding suggests the cancer drug irinotecan may feature prolonged gut activation, supporting the notion that the orally administered agent may have efficacy against cancers of the intestine.
The researchers concluded their “database provides a foundation for understanding individual contributions of diverse epithelial cells across the length of the human intestine and colon to maintain physiologic function.”
The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.
Single cell transcriptomics has revolutionized our understanding of complex tissues, as this technology enables the identification of rare and/or novel cell types. Gastrointestinal science has benefited greatly from these technical advances, with multiple studies profiling liver, pancreas, stomach and intestine in health and disease, both in mouse and human samples.
In sum, this study is the “final answer” for GI biologists needing a complete compendium of all genes active in the multitude of specialized human intestinal epithelial cells.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and the Center for Molecular Studies in Digestive and Liver Diseases at the University of Pennsylvania, Philadelphia. He declares having no conflicts of interest.
Single cell transcriptomics has revolutionized our understanding of complex tissues, as this technology enables the identification of rare and/or novel cell types. Gastrointestinal science has benefited greatly from these technical advances, with multiple studies profiling liver, pancreas, stomach and intestine in health and disease, both in mouse and human samples.
In sum, this study is the “final answer” for GI biologists needing a complete compendium of all genes active in the multitude of specialized human intestinal epithelial cells.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and the Center for Molecular Studies in Digestive and Liver Diseases at the University of Pennsylvania, Philadelphia. He declares having no conflicts of interest.
Single cell transcriptomics has revolutionized our understanding of complex tissues, as this technology enables the identification of rare and/or novel cell types. Gastrointestinal science has benefited greatly from these technical advances, with multiple studies profiling liver, pancreas, stomach and intestine in health and disease, both in mouse and human samples.
In sum, this study is the “final answer” for GI biologists needing a complete compendium of all genes active in the multitude of specialized human intestinal epithelial cells.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and the Center for Molecular Studies in Digestive and Liver Diseases at the University of Pennsylvania, Philadelphia. He declares having no conflicts of interest.
New research sheds light on how different cell types behave across all intestinal regions and demonstrates variations in gene expression between these cells across three independent organ donors.
Research led by Joseph Burclaff, PhD, of the University of North Carolina at Chapel Hill, explained that the regional differences observed in the study “highlight the importance of regional selection when studying the gut.” Dr. Burclaff and colleagues, whose findings were published online in Cellular and Molecular Gastroenterology and Hepatology, wrote that they hope their “database serves as a resource to understand how drugs affect the intestinal epithelium and as guidance for future precision medicine approaches.”
In the study, Dr. Burclaff and colleagues performed single-cell transcriptomics that covered the duodenum, jejunum, ileum, as well as ascending, descending, and transverse colon from three independently processed organ donors. The donors varied in age, race, and body mass index.
The investigators evaluated 12,590 single epithelial cells for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. The focus of the analyses was on intrinsic cell properties and their capacity for response to extrinsic signals found along the gut axis.
The research group assigned cells to 25 epithelial lineage clusters. According to the researchers, multiple accepted intestinal cell markers did not specifically mark all intestinal stem cells. In addition, the investigators explained that lysozyme expression was not unique to Paneth cells, and these cells lacked expression of certain “expected niche factors.” In fact, the researchers demonstrated lysozyme’s insufficiency for marking human Paneth cells.
Bestrophin-4þ (BEST4þ) cells, which expressed neuropeptide Y, demonstrated maturational differences between the colon and small intestine, suggesting organ-specific maturation for tuft and BEST4+ cells. In addition, the data from Dr. Burclaff and colleagues suggest BEST4+ cells are engaged in “diverse roles within the intestinal epithelium, laying the groundwork for functional studies.”
The researchers noted that “tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors.” Specifically, the researchers found these cells exhibit genes believed to be important for taste signaling, monitoring intestinal content, and signaling the immune system.
Certain classes of cell junctions, hormones, mucins, and nutrient absorption genes demonstrated “unappreciated regional expression differences across lineages,” the researchers wrote. The investigators added that the differential expression of receptors as well as drug targets across lineages demonstrated “biological variation and the potential for variegated responses.”
The researchers noted that while the regional differences identified in their study show the importance of regional selection during gut investigations, several previous colonic single-cell RNA sequencing studies did not specify the sample region or explain “if pooled samples are from consistent regions.”
In the study, the investigators also assessed how drugs may affect the intestinal epithelium and why certain side effects associated with pharmacologic agents occur. The researchers identified 498 drugs approved by the Food and Drug Administration that had 232 primary gene targets expressed in the gut epithelial dataset.
In their analysis, the researchers found that carboxylesterase-2, which metabolizes the drug irinotecan into biologically active SN-38, is the highest expressed phase 1 metabolism gene in the small intestine. Phase 2 enzyme UGT1A1, which inactivates SN-38, features low gut epithelial expression. The researchers explained that this finding suggests the cancer drug irinotecan may feature prolonged gut activation, supporting the notion that the orally administered agent may have efficacy against cancers of the intestine.
The researchers concluded their “database provides a foundation for understanding individual contributions of diverse epithelial cells across the length of the human intestine and colon to maintain physiologic function.”
The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.
New research sheds light on how different cell types behave across all intestinal regions and demonstrates variations in gene expression between these cells across three independent organ donors.
Research led by Joseph Burclaff, PhD, of the University of North Carolina at Chapel Hill, explained that the regional differences observed in the study “highlight the importance of regional selection when studying the gut.” Dr. Burclaff and colleagues, whose findings were published online in Cellular and Molecular Gastroenterology and Hepatology, wrote that they hope their “database serves as a resource to understand how drugs affect the intestinal epithelium and as guidance for future precision medicine approaches.”
In the study, Dr. Burclaff and colleagues performed single-cell transcriptomics that covered the duodenum, jejunum, ileum, as well as ascending, descending, and transverse colon from three independently processed organ donors. The donors varied in age, race, and body mass index.
The investigators evaluated 12,590 single epithelial cells for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. The focus of the analyses was on intrinsic cell properties and their capacity for response to extrinsic signals found along the gut axis.
The research group assigned cells to 25 epithelial lineage clusters. According to the researchers, multiple accepted intestinal cell markers did not specifically mark all intestinal stem cells. In addition, the investigators explained that lysozyme expression was not unique to Paneth cells, and these cells lacked expression of certain “expected niche factors.” In fact, the researchers demonstrated lysozyme’s insufficiency for marking human Paneth cells.
Bestrophin-4þ (BEST4þ) cells, which expressed neuropeptide Y, demonstrated maturational differences between the colon and small intestine, suggesting organ-specific maturation for tuft and BEST4+ cells. In addition, the data from Dr. Burclaff and colleagues suggest BEST4+ cells are engaged in “diverse roles within the intestinal epithelium, laying the groundwork for functional studies.”
The researchers noted that “tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors.” Specifically, the researchers found these cells exhibit genes believed to be important for taste signaling, monitoring intestinal content, and signaling the immune system.
Certain classes of cell junctions, hormones, mucins, and nutrient absorption genes demonstrated “unappreciated regional expression differences across lineages,” the researchers wrote. The investigators added that the differential expression of receptors as well as drug targets across lineages demonstrated “biological variation and the potential for variegated responses.”
The researchers noted that while the regional differences identified in their study show the importance of regional selection during gut investigations, several previous colonic single-cell RNA sequencing studies did not specify the sample region or explain “if pooled samples are from consistent regions.”
In the study, the investigators also assessed how drugs may affect the intestinal epithelium and why certain side effects associated with pharmacologic agents occur. The researchers identified 498 drugs approved by the Food and Drug Administration that had 232 primary gene targets expressed in the gut epithelial dataset.
In their analysis, the researchers found that carboxylesterase-2, which metabolizes the drug irinotecan into biologically active SN-38, is the highest expressed phase 1 metabolism gene in the small intestine. Phase 2 enzyme UGT1A1, which inactivates SN-38, features low gut epithelial expression. The researchers explained that this finding suggests the cancer drug irinotecan may feature prolonged gut activation, supporting the notion that the orally administered agent may have efficacy against cancers of the intestine.
The researchers concluded their “database provides a foundation for understanding individual contributions of diverse epithelial cells across the length of the human intestine and colon to maintain physiologic function.”
The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
White House announces long-COVID action plan
The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.
“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”
The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.
The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.
The United States has delivered more than 500 million vaccine doses to 114 countries.
Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.
New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.
Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.
“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.
Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.
Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.
A version of this article first appeared on WebMD.com.
The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.
“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”
The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.
The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.
The United States has delivered more than 500 million vaccine doses to 114 countries.
Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.
New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.
Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.
“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.
Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.
Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.
A version of this article first appeared on WebMD.com.
The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.
“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”
The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.
The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.
The United States has delivered more than 500 million vaccine doses to 114 countries.
Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.
New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.
Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.
“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.
Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.
Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.
A version of this article first appeared on WebMD.com.
Antiseizure medication appears safe in pregnancy
SEATTLE – , according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.
Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.
The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
A responsibility to ‘engage and educate’ patients
Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.
Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.
Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
Outdated attitudes still persist
Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.
MONEAD findings
The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.
Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.
At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.
The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.
The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.
SEATTLE – , according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.
Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.
The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
A responsibility to ‘engage and educate’ patients
Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.
Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.
Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
Outdated attitudes still persist
Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.
MONEAD findings
The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.
Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.
At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.
The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.
The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.
SEATTLE – , according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
The study follows results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which found no evidence of cognitive harm in children who were exposed in utero to antiepileptic drugs. “[In the NEAD study] we followed our cohort to age 6 and found them to have actually an improvement in cognition by about 4 IQ points by the time they got to age 6,” Kimford J. Meador, MD, said during a presentation of the results of the MONEAD study at the 2022 annual meeting of the American Academy of Neurology.
Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, atopic dermatitis, asthma, and diabetes in children, and reduced risk of diabetes, breast cancer, ovarian cancer, and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding.
The results of NEAD and MONEAD should reassure patients, according to Dr. Meador, professor of neurology at Stanford (Calif.) University. “Given the known multiple benefits of breastfeeding … women with epilepsy should be encouraged to breastfeed,” he said.
A responsibility to ‘engage and educate’ patients
Jennifer Hopp, MD, who served as a discussant for the presentation, underscored the need for neurologists to address pregnancy with female patients of childbearing agents. “The issues may include fertility, peripartum management, and outcomes that really go through the lifespan to also include issues of menopause,” Dr. Hopp, associate professor of neurology at the University of Maryland, Baltimore, said during her presentation.
Dr. Hopp noted one study showing lower rates of breastfeeding among mothers with epilepsy. “Breastfeeding rates in women with epilepsy are strikingly lower than in women who do not have epilepsy,” said Dr. Hopp. Another study showed that women with epilepsy were less likely to sustain breastfeeding after 6 weeks.
Dr. Hopp implored neurologists to address this. “It’s our responsibility to engage and educate our patients. These data provide us messaging to our patients that the newer drugs do not adversely affect outcome independently of their other exposure, and really support well-informed choices in breastfeeding,” said Dr. Hopp.
Outdated attitudes still persist
Dr. Meador referred to the stigma that surrounds epilepsy, including some state laws that called for sterilization of women with epilepsy that lasted until the 1960s. One might think that such attitudes are gone, “but it’s still there,” said Dr. Meador, who recounted a story a colleague told him about a woman on antiseizure medication. In the hospital, the nurse told her not to breastfeed. The neurological consult told her not to breastfeed. She breastfed anyway. “Then they reported her for child neglect, and that was just a few years ago. So I think the message needs to be loud and clear that we encourage [women with epilepsy] to breastfeed because we have the known benefits, and now several studies showing clearly no adverse effects of breastfeeding while taking antiseizure medications,” said Dr. Meador.
MONEAD findings
The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls.
Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.
At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770). The researchers did find associations with the mother’s IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.
The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033). “This is interesting (but) not to be overblown, because overall the children on levetiracetam did well. But it must be remembered that teratogens act in an exposure dependent manner, so we’re constantly in this balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, not too much on board where we increase the risk of teratogenicity in the child,” said Dr. Meador.
The study was funded by the National Institutes of Health. Dr. Meador and Dr. Hopp have no relevant financial disclosures.
AT AAN 2022