The SVS PSO is looking for a part-time Associate Medical Director. This person will be responsible for assisting the SVS PSO Medical Director and the SVS PSO staff, with guidance and over site in its clinical operations. The new associate director will be nominated by the SVS PSO Executive Committee and approved the SVS and the SVS Executive Board. He or she will serve a one-year term, with the opportunity to serve two additional one-year terms. There is a modest honorary associated with this position and the potential to advance into the role of SVS PSO Medical Director. Submit your application before Oct. 11 to be considered. Read the full job description here. Please email your completed resume to HRResumes@vascularsociety.org.

The SVS PSO is looking for a part-time Associate Medical Director. This person will be responsible for assisting the SVS PSO Medical Director and the SVS PSO staff, with guidance and over site in its clinical operations. The new associate director will be nominated by the SVS PSO Executive Committee and approved the SVS and the SVS Executive Board. He or she will serve a one-year term, with the opportunity to serve two additional one-year terms. There is a modest honorary associated with this position and the potential to advance into the role of SVS PSO Medical Director. Submit your application before Oct. 11 to be considered. Read the full job description here. Please email your completed resume to HRResumes@vascularsociety.org.

The SVS PSO is looking for a part-time Associate Medical Director. This person will be responsible for assisting the SVS PSO Medical Director and the SVS PSO staff, with guidance and over site in its clinical operations. The new associate director will be nominated by the SVS PSO Executive Committee and approved the SVS and the SVS Executive Board. He or she will serve a one-year term, with the opportunity to serve two additional one-year terms. There is a modest honorary associated with this position and the potential to advance into the role of SVS PSO Medical Director. Submit your application before Oct. 11 to be considered. Read the full job description here. Please email your completed resume to HRResumes@vascularsociety.org.

Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

If you are a young vascular surgeon from outside North America, consider applying for the International Scholars Program. Recipients of the award will receive a $5,000 stipend, spend two weeks in the U.S, visiting universities and clinics, and attend the 2020 VAM in Toronto. Scholars will work with a mentor to schedule various vascular program visits, including clinical, teaching and research programs. Apply before Sept. 16 to be considered. Learn more.

If you are a young vascular surgeon from outside North America, consider applying for the International Scholars Program. Recipients of the award will receive a $5,000 stipend, spend two weeks in the U.S, visiting universities and clinics, and attend the 2020 VAM in Toronto. Scholars will work with a mentor to schedule various vascular program visits, including clinical, teaching and research programs. Apply before Sept. 16 to be considered. Learn more.

If you are a young vascular surgeon from outside North America, consider applying for the International Scholars Program. Recipients of the award will receive a $5,000 stipend, spend two weeks in the U.S, visiting universities and clinics, and attend the 2020 VAM in Toronto. Scholars will work with a mentor to schedule various vascular program visits, including clinical, teaching and research programs. Apply before Sept. 16 to be considered. Learn more.

The SVS has officially announced its new Mentor Match program on its online community, SVSConnect. This program provides a simple way to match general surgery residents and medical students with vascular surgeons who will, ideally, help guide them on their career path. Our resident and student members have been awaiting a program like this, and it will only be successful if we have a large pool of Active SVS members enrolled as mentors. Mentees will be able to enroll soon, at which time the matching process will begin. Please look out for communication from us for when that occurs.  Questions? Reach out to communications@vascularsociety.org.

The SVS has officially announced its new Mentor Match program on its online community, SVSConnect. This program provides a simple way to match general surgery residents and medical students with vascular surgeons who will, ideally, help guide them on their career path. Our resident and student members have been awaiting a program like this, and it will only be successful if we have a large pool of Active SVS members enrolled as mentors. Mentees will be able to enroll soon, at which time the matching process will begin. Please look out for communication from us for when that occurs.  Questions? Reach out to communications@vascularsociety.org.

The SVS has officially announced its new Mentor Match program on its online community, SVSConnect. This program provides a simple way to match general surgery residents and medical students with vascular surgeons who will, ideally, help guide them on their career path. Our resident and student members have been awaiting a program like this, and it will only be successful if we have a large pool of Active SVS members enrolled as mentors. Mentees will be able to enroll soon, at which time the matching process will begin. Please look out for communication from us for when that occurs.  Questions? Reach out to communications@vascularsociety.org.

Join us as we celebrate all vascular nurses September 8 to 14 during Vascular Nurses Week. Be sure to let your nurses know how much you value them and their important contributions to your vascular team. You may also encourage your vascular nurses to join the SVS as affiliate members. Membership benefits include discounted meeting registrations, scholarship opportunities, leadership opportunities and more. Read more about Affiliate membership for vascular nurses here.

Join us as we celebrate all vascular nurses September 8 to 14 during Vascular Nurses Week. Be sure to let your nurses know how much you value them and their important contributions to your vascular team. You may also encourage your vascular nurses to join the SVS as affiliate members. Membership benefits include discounted meeting registrations, scholarship opportunities, leadership opportunities and more. Read more about Affiliate membership for vascular nurses here.

Join us as we celebrate all vascular nurses September 8 to 14 during Vascular Nurses Week. Be sure to let your nurses know how much you value them and their important contributions to your vascular team. You may also encourage your vascular nurses to join the SVS as affiliate members. Membership benefits include discounted meeting registrations, scholarship opportunities, leadership opportunities and more. Read more about Affiliate membership for vascular nurses here.

Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?

ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D is protective in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.

The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup ­an­alysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).

In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, ­including risk for all-cause serious adverse events (AOR, 0.98).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, as it is an ingrained practice for many providers.

In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).

Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?

ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D is protective in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.

The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup ­an­alysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).

In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, ­including risk for all-cause serious adverse events (AOR, 0.98).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, as it is an ingrained practice for many providers.

In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).

Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?

ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D is protective in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.

The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup ­an­alysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).

In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, ­including risk for all-cause serious adverse events (AOR, 0.98).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, as it is an ingrained practice for many providers.

In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).

COPENHAGEN – A first-in-class, once-daily, orally administered neuroactive steroid known for now as SAGE-217 aced all of its primary and secondary outcomes for the treatment of postpartum depression in the phase 3, randomized, double-blind, placebo-controlled ROBIN study, Eduard Vieta, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“I think this changes the paradigm in the treatment of postpartum depression,” declared Dr. Vieta, professor of psychiatry and head of the bipolar disorders program at the University of Barcelona.

Like brexanolone (Zulresso), an intravenous formulation of allopregnanolone approved by the Food and Drug Administration in March 2019 as the first-ever drug specifically targeting postpartum depression, SAGE-217 is a positive allosteric modifier of synaptic and extrasynaptic GABA-A receptors. That differentiates the two drugs from benzodiazepines, which target only synaptic receptors. Both brexanolone and SAGE-217 are drugs developed by Sage Therapeutics. But SAGE-217, an investigational agent, is vastly more convenient to use than brexanolone since, as an oral drug, it doesn’t require hospitalization for intravenous administration.

Dr. Vieta ticked off five reasons why he considers SAGE-217 a game changer in the treatment of postpartum depression: “It’s an amazingly effective compound, with an effect size that’s bigger than we usually see with antidepressants. It has an early onset of action, similar to what we see with glutaminergic agents, although with an opposite mechanism: enhancing GABA rather than opposing glutamate. It has excellent tolerability, similar to placebo. It’s made to be used orally, a major advantage over other drugs that are available or close to becoming available, which have to be given IV. And last but not least, a patient will get it for only 2 weeks. The treatment can be stopped after 2 weeks, and there is long-term improvement.”

The ROBIN trial included 151 patients with postpartum depression as defined by a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 26 who were randomized double-blind to 14 days of SAGE-217 at 30 mg once daily or to placebo. The primary endpoint was the change in HAM-D scores between baseline and day 15. The key finding was that the SAGE-217 group averaged a 17.8-point reduction, significantly greater than the 13.6-point improvement with placebo. This advantage was maintained at assessment on day 45 – a full month after treatment stopped – with a 24.8-point improvement over baseline in the SAGE-217 recipients, compared with a 19-point reduction in controls. The advantage favoring SAGE-217 was significant as early as day 3, the first assessment, at which point the average improvement in HAM-D was 12.5 points, compared with 9.8 points in controls.

Other secondary endpoints included change from baseline to day 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS): a 22.8-point improvement in the SAGE-217 group, significantly greater than the 17.6-point improvement in the placebo arm. The same pattern was evident at day 45, with reductions in MADRS of 24.8 and 19 points, respectively, in the SAGE-217 and placebo groups.

Another key prespecified secondary endpoint was change in scores on the Hamilton Rating Scale for Anxiety through day 15. There was a mean 16.6-point drop in the active treatment arm, compared with a 12.7-point improvement with placebo, again a statistically significant and clinically meaningful between-group difference. This is an important endpoint because comorbid anxiety is common in the setting of postpartum depression, the psychiatrist continued.

The SAGE-217 group also demonstrated significantly higher rates of HAM-D response as defined by a 50% or greater reduction in total score at day 15, as well as in HAM-D remission, which entails having a score of 7 or less.

Treatment-emergent adverse events in the SAGE-217 and placebo arms were similar in frequency and type. The most common adverse events associated with SAGE-217 – all occurring in single-digit frequencies – were sleepiness, headache, dizziness, upper respiratory infections, and diarrhea. There was no signal of increased suicidal thoughts or behavior as assessed using the Columbia Suicide Severity Rating Scale.

SAGE-217 also is the focus of an ongoing pivotal phase 3 trial in patients with major depression. In addition, the drug is under study for bipolar depression, major depressive disorder with comorbid insomnia, and generalized anxiety disorder.

Dr. Vieta reported serving on advisory boards for Sage Therapeutics, the study sponsor, as well as for two dozen other pharmaceutical companies. He receives research funding from the Spanish Ministry of Science and Education, the Stanley Medical Research Institute, and more than a dozen pharmaceutical companies.

bjancin@mdedge.com

COPENHAGEN – A first-in-class, once-daily, orally administered neuroactive steroid known for now as SAGE-217 aced all of its primary and secondary outcomes for the treatment of postpartum depression in the phase 3, randomized, double-blind, placebo-controlled ROBIN study, Eduard Vieta, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“I think this changes the paradigm in the treatment of postpartum depression,” declared Dr. Vieta, professor of psychiatry and head of the bipolar disorders program at the University of Barcelona.

Like brexanolone (Zulresso), an intravenous formulation of allopregnanolone approved by the Food and Drug Administration in March 2019 as the first-ever drug specifically targeting postpartum depression, SAGE-217 is a positive allosteric modifier of synaptic and extrasynaptic GABA-A receptors. That differentiates the two drugs from benzodiazepines, which target only synaptic receptors. Both brexanolone and SAGE-217 are drugs developed by Sage Therapeutics. But SAGE-217, an investigational agent, is vastly more convenient to use than brexanolone since, as an oral drug, it doesn’t require hospitalization for intravenous administration.

Dr. Vieta ticked off five reasons why he considers SAGE-217 a game changer in the treatment of postpartum depression: “It’s an amazingly effective compound, with an effect size that’s bigger than we usually see with antidepressants. It has an early onset of action, similar to what we see with glutaminergic agents, although with an opposite mechanism: enhancing GABA rather than opposing glutamate. It has excellent tolerability, similar to placebo. It’s made to be used orally, a major advantage over other drugs that are available or close to becoming available, which have to be given IV. And last but not least, a patient will get it for only 2 weeks. The treatment can be stopped after 2 weeks, and there is long-term improvement.”

The ROBIN trial included 151 patients with postpartum depression as defined by a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 26 who were randomized double-blind to 14 days of SAGE-217 at 30 mg once daily or to placebo. The primary endpoint was the change in HAM-D scores between baseline and day 15. The key finding was that the SAGE-217 group averaged a 17.8-point reduction, significantly greater than the 13.6-point improvement with placebo. This advantage was maintained at assessment on day 45 – a full month after treatment stopped – with a 24.8-point improvement over baseline in the SAGE-217 recipients, compared with a 19-point reduction in controls. The advantage favoring SAGE-217 was significant as early as day 3, the first assessment, at which point the average improvement in HAM-D was 12.5 points, compared with 9.8 points in controls.

Other secondary endpoints included change from baseline to day 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS): a 22.8-point improvement in the SAGE-217 group, significantly greater than the 17.6-point improvement in the placebo arm. The same pattern was evident at day 45, with reductions in MADRS of 24.8 and 19 points, respectively, in the SAGE-217 and placebo groups.

Another key prespecified secondary endpoint was change in scores on the Hamilton Rating Scale for Anxiety through day 15. There was a mean 16.6-point drop in the active treatment arm, compared with a 12.7-point improvement with placebo, again a statistically significant and clinically meaningful between-group difference. This is an important endpoint because comorbid anxiety is common in the setting of postpartum depression, the psychiatrist continued.

The SAGE-217 group also demonstrated significantly higher rates of HAM-D response as defined by a 50% or greater reduction in total score at day 15, as well as in HAM-D remission, which entails having a score of 7 or less.

Treatment-emergent adverse events in the SAGE-217 and placebo arms were similar in frequency and type. The most common adverse events associated with SAGE-217 – all occurring in single-digit frequencies – were sleepiness, headache, dizziness, upper respiratory infections, and diarrhea. There was no signal of increased suicidal thoughts or behavior as assessed using the Columbia Suicide Severity Rating Scale.

SAGE-217 also is the focus of an ongoing pivotal phase 3 trial in patients with major depression. In addition, the drug is under study for bipolar depression, major depressive disorder with comorbid insomnia, and generalized anxiety disorder.

Dr. Vieta reported serving on advisory boards for Sage Therapeutics, the study sponsor, as well as for two dozen other pharmaceutical companies. He receives research funding from the Spanish Ministry of Science and Education, the Stanley Medical Research Institute, and more than a dozen pharmaceutical companies.

bjancin@mdedge.com

COPENHAGEN – A first-in-class, once-daily, orally administered neuroactive steroid known for now as SAGE-217 aced all of its primary and secondary outcomes for the treatment of postpartum depression in the phase 3, randomized, double-blind, placebo-controlled ROBIN study, Eduard Vieta, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“I think this changes the paradigm in the treatment of postpartum depression,” declared Dr. Vieta, professor of psychiatry and head of the bipolar disorders program at the University of Barcelona.

Like brexanolone (Zulresso), an intravenous formulation of allopregnanolone approved by the Food and Drug Administration in March 2019 as the first-ever drug specifically targeting postpartum depression, SAGE-217 is a positive allosteric modifier of synaptic and extrasynaptic GABA-A receptors. That differentiates the two drugs from benzodiazepines, which target only synaptic receptors. Both brexanolone and SAGE-217 are drugs developed by Sage Therapeutics. But SAGE-217, an investigational agent, is vastly more convenient to use than brexanolone since, as an oral drug, it doesn’t require hospitalization for intravenous administration.

Dr. Vieta ticked off five reasons why he considers SAGE-217 a game changer in the treatment of postpartum depression: “It’s an amazingly effective compound, with an effect size that’s bigger than we usually see with antidepressants. It has an early onset of action, similar to what we see with glutaminergic agents, although with an opposite mechanism: enhancing GABA rather than opposing glutamate. It has excellent tolerability, similar to placebo. It’s made to be used orally, a major advantage over other drugs that are available or close to becoming available, which have to be given IV. And last but not least, a patient will get it for only 2 weeks. The treatment can be stopped after 2 weeks, and there is long-term improvement.”

The ROBIN trial included 151 patients with postpartum depression as defined by a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 26 who were randomized double-blind to 14 days of SAGE-217 at 30 mg once daily or to placebo. The primary endpoint was the change in HAM-D scores between baseline and day 15. The key finding was that the SAGE-217 group averaged a 17.8-point reduction, significantly greater than the 13.6-point improvement with placebo. This advantage was maintained at assessment on day 45 – a full month after treatment stopped – with a 24.8-point improvement over baseline in the SAGE-217 recipients, compared with a 19-point reduction in controls. The advantage favoring SAGE-217 was significant as early as day 3, the first assessment, at which point the average improvement in HAM-D was 12.5 points, compared with 9.8 points in controls.

Other secondary endpoints included change from baseline to day 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS): a 22.8-point improvement in the SAGE-217 group, significantly greater than the 17.6-point improvement in the placebo arm. The same pattern was evident at day 45, with reductions in MADRS of 24.8 and 19 points, respectively, in the SAGE-217 and placebo groups.

Another key prespecified secondary endpoint was change in scores on the Hamilton Rating Scale for Anxiety through day 15. There was a mean 16.6-point drop in the active treatment arm, compared with a 12.7-point improvement with placebo, again a statistically significant and clinically meaningful between-group difference. This is an important endpoint because comorbid anxiety is common in the setting of postpartum depression, the psychiatrist continued.

The SAGE-217 group also demonstrated significantly higher rates of HAM-D response as defined by a 50% or greater reduction in total score at day 15, as well as in HAM-D remission, which entails having a score of 7 or less.

Treatment-emergent adverse events in the SAGE-217 and placebo arms were similar in frequency and type. The most common adverse events associated with SAGE-217 – all occurring in single-digit frequencies – were sleepiness, headache, dizziness, upper respiratory infections, and diarrhea. There was no signal of increased suicidal thoughts or behavior as assessed using the Columbia Suicide Severity Rating Scale.

SAGE-217 also is the focus of an ongoing pivotal phase 3 trial in patients with major depression. In addition, the drug is under study for bipolar depression, major depressive disorder with comorbid insomnia, and generalized anxiety disorder.

Dr. Vieta reported serving on advisory boards for Sage Therapeutics, the study sponsor, as well as for two dozen other pharmaceutical companies. He receives research funding from the Spanish Ministry of Science and Education, the Stanley Medical Research Institute, and more than a dozen pharmaceutical companies.

bjancin@mdedge.com

To the Editor:

A 53-year-old woman presented to our dermatology clinic with a painful growth on the right ear of 2 months’ duration. A complete review of systems was negative except for an isolated episode of shortness of breath prior to presentation that resolved without intervention. During this episode, her primary care physician made a diagnosis of chronic obstructive pulmonary disease based on a chest radiograph. The patient reported minimal tobacco use, specifically that she had smoked a few cigarettes daily for several years but had quit 6 months prior to the current presentation.

Physical examination at our clinic revealed a tender, hyperkeratotic, cone-shaped papule with mild erythema on the right antitragus that was consistent with a cutaneous horn (Figure 1). Although she denied any other skin lesions, further evaluation revealed a cluster of firm flesh-colored papules surrounding the left medial canthus as well as a pink scaly plaque on the posterior neck.

Studies analyzing the underlying diagnoses and clinical features of cutaneous horns are limited. In a large retrospective study of 643 cutaneous horns, 61% were benign, 23% were premalignant, and 16% were malignant. In this study, 4 features were associated with premalignant or malignant pathology: (1) older age (mid- 60s to 70s); (2) male sex; (3) location on the nose, pinnae, dorsal hands, scalp, forearms, or face; and (4) a wide base (4.4 mm or larger) and a lower height-to-base ratio than benign lesions.¹ Two additional studies of more than 200 horns each showed higher rates of premalignant horns (42% and 38%, respectively) with malignancy found in 7% and 20% of horns, respectively.^2,3 One prospective study sought to identify clinical and dermatoscopic features of SCCs underlying cutaneous horns, concluding that SCC diagnosis was more likely if a horn had (1) a height less than the diameter of its base, (2) a lack of terrace morphology (a dermatoscopic feature defined as horizontal parallel layers of keratin), (3) erythema at the base, and (4) the presence of pain.⁴

Our patient had a cutaneous horn on the pinna that was painful, wider than it was tall, and erythematous at the base, suggesting a malignant process; however, a complete cutaneous physical examination revealed other skin lesions that were concerning for sarcoidosis and raised suspicion that the horn also was a manifestation of the same inflammatory process.

Although unusual, cutaneous sarcoidosis presenting as a cutaneous horn is not unexpected. In a histopathologic study of 62 cases of cutaneous sarcoidosis, 79% (49/62) showed epidermal changes and 13% (8/62) demonstrated hyperkeratosis. Other epidermal changes included parakeratosis (16% [10/62]), acanthosis (10% [6/62]), and epidermal atrophy (57% [35/62]).⁵ The spectrum of epidermal pathology in cutaneous sarcoidosis is evident in its well-documented verrucous, psoriasiform, and ichthyosiform presentations. For completeness, cutaneous horn is added to the list of clinical morphologies for this “great imitator” of cutaneous diseases.

To the Editor:

A 53-year-old woman presented to our dermatology clinic with a painful growth on the right ear of 2 months’ duration. A complete review of systems was negative except for an isolated episode of shortness of breath prior to presentation that resolved without intervention. During this episode, her primary care physician made a diagnosis of chronic obstructive pulmonary disease based on a chest radiograph. The patient reported minimal tobacco use, specifically that she had smoked a few cigarettes daily for several years but had quit 6 months prior to the current presentation.

Physical examination at our clinic revealed a tender, hyperkeratotic, cone-shaped papule with mild erythema on the right antitragus that was consistent with a cutaneous horn (Figure 1). Although she denied any other skin lesions, further evaluation revealed a cluster of firm flesh-colored papules surrounding the left medial canthus as well as a pink scaly plaque on the posterior neck.

Studies analyzing the underlying diagnoses and clinical features of cutaneous horns are limited. In a large retrospective study of 643 cutaneous horns, 61% were benign, 23% were premalignant, and 16% were malignant. In this study, 4 features were associated with premalignant or malignant pathology: (1) older age (mid- 60s to 70s); (2) male sex; (3) location on the nose, pinnae, dorsal hands, scalp, forearms, or face; and (4) a wide base (4.4 mm or larger) and a lower height-to-base ratio than benign lesions.¹ Two additional studies of more than 200 horns each showed higher rates of premalignant horns (42% and 38%, respectively) with malignancy found in 7% and 20% of horns, respectively.^2,3 One prospective study sought to identify clinical and dermatoscopic features of SCCs underlying cutaneous horns, concluding that SCC diagnosis was more likely if a horn had (1) a height less than the diameter of its base, (2) a lack of terrace morphology (a dermatoscopic feature defined as horizontal parallel layers of keratin), (3) erythema at the base, and (4) the presence of pain.⁴

Our patient had a cutaneous horn on the pinna that was painful, wider than it was tall, and erythematous at the base, suggesting a malignant process; however, a complete cutaneous physical examination revealed other skin lesions that were concerning for sarcoidosis and raised suspicion that the horn also was a manifestation of the same inflammatory process.

Although unusual, cutaneous sarcoidosis presenting as a cutaneous horn is not unexpected. In a histopathologic study of 62 cases of cutaneous sarcoidosis, 79% (49/62) showed epidermal changes and 13% (8/62) demonstrated hyperkeratosis. Other epidermal changes included parakeratosis (16% [10/62]), acanthosis (10% [6/62]), and epidermal atrophy (57% [35/62]).⁵ The spectrum of epidermal pathology in cutaneous sarcoidosis is evident in its well-documented verrucous, psoriasiform, and ichthyosiform presentations. For completeness, cutaneous horn is added to the list of clinical morphologies for this “great imitator” of cutaneous diseases.

To the Editor:

A 53-year-old woman presented to our dermatology clinic with a painful growth on the right ear of 2 months’ duration. A complete review of systems was negative except for an isolated episode of shortness of breath prior to presentation that resolved without intervention. During this episode, her primary care physician made a diagnosis of chronic obstructive pulmonary disease based on a chest radiograph. The patient reported minimal tobacco use, specifically that she had smoked a few cigarettes daily for several years but had quit 6 months prior to the current presentation.

Physical examination at our clinic revealed a tender, hyperkeratotic, cone-shaped papule with mild erythema on the right antitragus that was consistent with a cutaneous horn (Figure 1). Although she denied any other skin lesions, further evaluation revealed a cluster of firm flesh-colored papules surrounding the left medial canthus as well as a pink scaly plaque on the posterior neck.

Studies analyzing the underlying diagnoses and clinical features of cutaneous horns are limited. In a large retrospective study of 643 cutaneous horns, 61% were benign, 23% were premalignant, and 16% were malignant. In this study, 4 features were associated with premalignant or malignant pathology: (1) older age (mid- 60s to 70s); (2) male sex; (3) location on the nose, pinnae, dorsal hands, scalp, forearms, or face; and (4) a wide base (4.4 mm or larger) and a lower height-to-base ratio than benign lesions.¹ Two additional studies of more than 200 horns each showed higher rates of premalignant horns (42% and 38%, respectively) with malignancy found in 7% and 20% of horns, respectively.^2,3 One prospective study sought to identify clinical and dermatoscopic features of SCCs underlying cutaneous horns, concluding that SCC diagnosis was more likely if a horn had (1) a height less than the diameter of its base, (2) a lack of terrace morphology (a dermatoscopic feature defined as horizontal parallel layers of keratin), (3) erythema at the base, and (4) the presence of pain.⁴

Our patient had a cutaneous horn on the pinna that was painful, wider than it was tall, and erythematous at the base, suggesting a malignant process; however, a complete cutaneous physical examination revealed other skin lesions that were concerning for sarcoidosis and raised suspicion that the horn also was a manifestation of the same inflammatory process.

Although unusual, cutaneous sarcoidosis presenting as a cutaneous horn is not unexpected. In a histopathologic study of 62 cases of cutaneous sarcoidosis, 79% (49/62) showed epidermal changes and 13% (8/62) demonstrated hyperkeratosis. Other epidermal changes included parakeratosis (16% [10/62]), acanthosis (10% [6/62]), and epidermal atrophy (57% [35/62]).⁵ The spectrum of epidermal pathology in cutaneous sarcoidosis is evident in its well-documented verrucous, psoriasiform, and ichthyosiform presentations. For completeness, cutaneous horn is added to the list of clinical morphologies for this “great imitator” of cutaneous diseases.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

jremaly@mdedge.com

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

jremaly@mdedge.com

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.

A prosthetic leg that elicits the sensation of knee motion and the feeling of the sole of the foot touching the ground may improve walking performance and reduce phantom limb pain, according to a proof-of-concept study with two patients.

Huntstock/thinkstockphotos

With the bionic leg system, the patients performed better during clinically important tests indoors and outdoors, study author Stanisa Raspopovic, PhD, explained during a press briefing about the research. The findings were published in Nature Medicine.

The results indicate that the use of sensory feedback “could be common practice” in prosthetic devices in the future, he said. Dr. Raspopovic is a researcher at Swiss Federal Institute of Technology Zürich and a founder of SensArs Neuroprosthetics, which is based in Lausanne, Switzerland.

Neural prosthetics allow the nervous system and external devices to interact. These brain-machine interfaces may improve quality of life for patients with brain or spinal cord injuries, degenerative disease, or loss of limbs.

“Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users,” the study authors wrote. Users may also have high levels of mental and physical fatigue, and the lack of physiologic feedback from the extremity to the brain may contribute to the generation of phantom limb pain.

To evaluate whether neural sensory feedback restoration could address these issues, investigators conducted a study with two patients who had undergone transfemoral amputations as a result of traumatic events. The patients were implanted with four intraneural stimulation electrodes in the remaining tibial nerve. The prosthetic leg device included sensors to represent foot touch and pressure and knee joint angle. The sensors transmitted sensory signals to the nervous system through the stimulation electrodes in the tibial nerve.

When the patients walked outdoors over a path traced in the sand, “participants’ speeds were significantly higher when sensory feedback was provided,” the authors wrote. One participant walked 3.56 m/min faster, and the other walked 5.68 m/min faster.

The participants also rated their confidence in the prosthesis on a scale from 0 to 10. For patient 1, self-rated confidence improved from 4.85 to 7.71 with the device. Patient 2 reported a confidence level that climbed from 2.7 to 5.55.

When tested indoors, both patients reached a 0.5 km/hour higher speed on the treadmill when stimulation was provided and both had a lower mean rate of oxygen uptake during the sensory feedback trials, the study authors reported.

Levels of phantom limb pain also decreased significantly after 10-minute stimulation sessions, but not during control sessions.

Longer studies with more patients are required, and fully implantable devices without transcutaneous cables need to be developed, the authors wrote.

Grants from the European Research Council, European Commission, and Swiss National Science Foundation funded the research. Dr. Raspopovic and two coauthors hold shares of SensArs Neuroprosthetics, a start-up company dealing with the commercialization of neurocontrolled artificial limbs.

jremaly@mdedge.com

SOURCE: Petrini FM et al. Nat Med. 2019 Sep 9. doi: 10.1038/s41591-019-0567-3.