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Complement Inhibitor Scores Impressive Data in CIDP
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
FROM AAN 2024
Prospect of Better Hours, Less Burnout Fuels Locum Tenens
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
Vaccine Against Urinary Tract Infections in Development
Urinary tract infections are among the most common bacterial infections. They can be painful, require antibiotic treatments, and recur in 20%-30% of cases. With the risk for the emergence or increase of resistance to antibiotics, it is important to search for potential therapeutic alternatives to treat or prevent urinary tract infections.
The MV140 Vaccine
The MV140 vaccine is produced by the Spanish pharmaceutical company Immunotek. MV140, known as Uromune, consists of a suspension of whole heat-inactivated bacteria in glycerol, sodium chloride, an artificial pineapple flavor, and water. It includes equal percentages of strains from four bacterial species (V121 Escherichia coli, V113 Klebsiella pneumoniae, V125 Enterococcus faecalis, and V127 Proteus vulgaris). MV140 is administered sublingually by spraying two 100-µL doses daily for 3 months.
The vaccine is in phase 2-3 of development. It is available under special access programs outside of marketing authorization in 26 countries, including Spain, Portugal, the United Kingdom, Lithuania, the Netherlands, Sweden, Norway, Australia, New Zealand, and Chile. Recently, MV140 was approved in Mexico and the Dominican Republic and submitted to Health Canada for registration.
A randomized study published in 2022 showed the vaccine›s efficacy in preventing urinary tract infections over 9 months. In total, 240 women with a urinary tract infection received MV140 for either 3 or 6 months or a placebo for 6 months. The primary outcome was the number of urinary tract infection episodes during the 9-month study period after vaccination.
In this pivotal study, MV140 administration for 3 and 6 months was associated with a significant reduction in the median number of urinary tract infection episodes, from 3.0 to 0.0 compared with the placebo during the 9-month efficacy period. The median time to the first urinary tract infection after 3 months of treatment was 275.0 days in the MV140 groups compared with 48.0 days in the placebo group.
Nine-Year Follow-Up
On April 6 at the 2024 congress of The European Association of Urology, urologists from the Royal Berkshire NHS Foundation Trust presented the results of a study evaluating the MV140 vaccine spray for long-term prevention of bacterial urinary tract infections.
This was a prospective cohort study involving 89 participants (72 women and 17 men) older than 18 years with recurrent urinary tract infections who received a course of MV140 for 3 months. Participants had no urinary tract infection when offered the vaccine and had no other urinary abnormalities (such as tumors, stones, or kidney infections).
Postvaccination follow-up was conducted over a 9-year period, during which researchers analyzed the data from the electronic health records of their initial cohort. They queried participants about the occurrence of urinary tract infections since receiving the vaccine and about potential related side effects. Thus, the results were self-reported.
Long-Term Efficacy
In this cohort, 48 participants (59%) reported having no infections during the 9-year follow-up. In the cohort of 89 participants, the average period without infection was 54.7 months (4.5 years; 56.7 months for women and 44.3 months for men). No vaccine-related side effects were observed.
The study’s limitations included the small number of participants and the collection of self-reported data. Furthermore, all cases were simple urinary tract infections without complications.
The authors concluded that “9 years after first receiving the sublingual spray MV140 vaccine, 54% of participants remained free from urinary tract infection.” For them, “this vaccine is safe in the long-term, and our participants reported fewer urinary tract infections and, if any, they were less severe.”
Vaccination could thus be an alternative to antibiotic treatments and could help combat the emergence of antibiotic resistance. The full study results should be published by the end of 2024.
Other studies are planned to evaluate the efficacy and safety of the MV140 vaccine in older patients residing in long-term care homes, in children suffering from acute urinary tract infections, and in adults suffering from complicated acute urinary tract infections (for example, patients with a catheter or with a neurogenic bladder).
This story was translated from JIM, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Urinary tract infections are among the most common bacterial infections. They can be painful, require antibiotic treatments, and recur in 20%-30% of cases. With the risk for the emergence or increase of resistance to antibiotics, it is important to search for potential therapeutic alternatives to treat or prevent urinary tract infections.
The MV140 Vaccine
The MV140 vaccine is produced by the Spanish pharmaceutical company Immunotek. MV140, known as Uromune, consists of a suspension of whole heat-inactivated bacteria in glycerol, sodium chloride, an artificial pineapple flavor, and water. It includes equal percentages of strains from four bacterial species (V121 Escherichia coli, V113 Klebsiella pneumoniae, V125 Enterococcus faecalis, and V127 Proteus vulgaris). MV140 is administered sublingually by spraying two 100-µL doses daily for 3 months.
The vaccine is in phase 2-3 of development. It is available under special access programs outside of marketing authorization in 26 countries, including Spain, Portugal, the United Kingdom, Lithuania, the Netherlands, Sweden, Norway, Australia, New Zealand, and Chile. Recently, MV140 was approved in Mexico and the Dominican Republic and submitted to Health Canada for registration.
A randomized study published in 2022 showed the vaccine›s efficacy in preventing urinary tract infections over 9 months. In total, 240 women with a urinary tract infection received MV140 for either 3 or 6 months or a placebo for 6 months. The primary outcome was the number of urinary tract infection episodes during the 9-month study period after vaccination.
In this pivotal study, MV140 administration for 3 and 6 months was associated with a significant reduction in the median number of urinary tract infection episodes, from 3.0 to 0.0 compared with the placebo during the 9-month efficacy period. The median time to the first urinary tract infection after 3 months of treatment was 275.0 days in the MV140 groups compared with 48.0 days in the placebo group.
Nine-Year Follow-Up
On April 6 at the 2024 congress of The European Association of Urology, urologists from the Royal Berkshire NHS Foundation Trust presented the results of a study evaluating the MV140 vaccine spray for long-term prevention of bacterial urinary tract infections.
This was a prospective cohort study involving 89 participants (72 women and 17 men) older than 18 years with recurrent urinary tract infections who received a course of MV140 for 3 months. Participants had no urinary tract infection when offered the vaccine and had no other urinary abnormalities (such as tumors, stones, or kidney infections).
Postvaccination follow-up was conducted over a 9-year period, during which researchers analyzed the data from the electronic health records of their initial cohort. They queried participants about the occurrence of urinary tract infections since receiving the vaccine and about potential related side effects. Thus, the results were self-reported.
Long-Term Efficacy
In this cohort, 48 participants (59%) reported having no infections during the 9-year follow-up. In the cohort of 89 participants, the average period without infection was 54.7 months (4.5 years; 56.7 months for women and 44.3 months for men). No vaccine-related side effects were observed.
The study’s limitations included the small number of participants and the collection of self-reported data. Furthermore, all cases were simple urinary tract infections without complications.
The authors concluded that “9 years after first receiving the sublingual spray MV140 vaccine, 54% of participants remained free from urinary tract infection.” For them, “this vaccine is safe in the long-term, and our participants reported fewer urinary tract infections and, if any, they were less severe.”
Vaccination could thus be an alternative to antibiotic treatments and could help combat the emergence of antibiotic resistance. The full study results should be published by the end of 2024.
Other studies are planned to evaluate the efficacy and safety of the MV140 vaccine in older patients residing in long-term care homes, in children suffering from acute urinary tract infections, and in adults suffering from complicated acute urinary tract infections (for example, patients with a catheter or with a neurogenic bladder).
This story was translated from JIM, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Urinary tract infections are among the most common bacterial infections. They can be painful, require antibiotic treatments, and recur in 20%-30% of cases. With the risk for the emergence or increase of resistance to antibiotics, it is important to search for potential therapeutic alternatives to treat or prevent urinary tract infections.
The MV140 Vaccine
The MV140 vaccine is produced by the Spanish pharmaceutical company Immunotek. MV140, known as Uromune, consists of a suspension of whole heat-inactivated bacteria in glycerol, sodium chloride, an artificial pineapple flavor, and water. It includes equal percentages of strains from four bacterial species (V121 Escherichia coli, V113 Klebsiella pneumoniae, V125 Enterococcus faecalis, and V127 Proteus vulgaris). MV140 is administered sublingually by spraying two 100-µL doses daily for 3 months.
The vaccine is in phase 2-3 of development. It is available under special access programs outside of marketing authorization in 26 countries, including Spain, Portugal, the United Kingdom, Lithuania, the Netherlands, Sweden, Norway, Australia, New Zealand, and Chile. Recently, MV140 was approved in Mexico and the Dominican Republic and submitted to Health Canada for registration.
A randomized study published in 2022 showed the vaccine›s efficacy in preventing urinary tract infections over 9 months. In total, 240 women with a urinary tract infection received MV140 for either 3 or 6 months or a placebo for 6 months. The primary outcome was the number of urinary tract infection episodes during the 9-month study period after vaccination.
In this pivotal study, MV140 administration for 3 and 6 months was associated with a significant reduction in the median number of urinary tract infection episodes, from 3.0 to 0.0 compared with the placebo during the 9-month efficacy period. The median time to the first urinary tract infection after 3 months of treatment was 275.0 days in the MV140 groups compared with 48.0 days in the placebo group.
Nine-Year Follow-Up
On April 6 at the 2024 congress of The European Association of Urology, urologists from the Royal Berkshire NHS Foundation Trust presented the results of a study evaluating the MV140 vaccine spray for long-term prevention of bacterial urinary tract infections.
This was a prospective cohort study involving 89 participants (72 women and 17 men) older than 18 years with recurrent urinary tract infections who received a course of MV140 for 3 months. Participants had no urinary tract infection when offered the vaccine and had no other urinary abnormalities (such as tumors, stones, or kidney infections).
Postvaccination follow-up was conducted over a 9-year period, during which researchers analyzed the data from the electronic health records of their initial cohort. They queried participants about the occurrence of urinary tract infections since receiving the vaccine and about potential related side effects. Thus, the results were self-reported.
Long-Term Efficacy
In this cohort, 48 participants (59%) reported having no infections during the 9-year follow-up. In the cohort of 89 participants, the average period without infection was 54.7 months (4.5 years; 56.7 months for women and 44.3 months for men). No vaccine-related side effects were observed.
The study’s limitations included the small number of participants and the collection of self-reported data. Furthermore, all cases were simple urinary tract infections without complications.
The authors concluded that “9 years after first receiving the sublingual spray MV140 vaccine, 54% of participants remained free from urinary tract infection.” For them, “this vaccine is safe in the long-term, and our participants reported fewer urinary tract infections and, if any, they were less severe.”
Vaccination could thus be an alternative to antibiotic treatments and could help combat the emergence of antibiotic resistance. The full study results should be published by the end of 2024.
Other studies are planned to evaluate the efficacy and safety of the MV140 vaccine in older patients residing in long-term care homes, in children suffering from acute urinary tract infections, and in adults suffering from complicated acute urinary tract infections (for example, patients with a catheter or with a neurogenic bladder).
This story was translated from JIM, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
This Tech Will Change Your Practice Sooner Than You Think
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Childhood Weight-Related Trauma Can Last into Adulthood
This can continue to be the case as long as two decades after the childhood experiences.
“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.
Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.
The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
Effects Unrelated to Weight
Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.
The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.
“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.
Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.
Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
Promote Healthy, Not Thin
Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.
“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.
Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.
Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.
A version of this article appeared on Medscape.com.
This can continue to be the case as long as two decades after the childhood experiences.
“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.
Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.
The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
Effects Unrelated to Weight
Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.
The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.
“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.
Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.
Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
Promote Healthy, Not Thin
Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.
“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.
Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.
Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.
A version of this article appeared on Medscape.com.
This can continue to be the case as long as two decades after the childhood experiences.
“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.
Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.
The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
Effects Unrelated to Weight
Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.
The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.
“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.
Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.
Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
Promote Healthy, Not Thin
Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.
“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.
Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.
Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.
A version of this article appeared on Medscape.com.
FROM THE LANCET REGIONAL HEALTH
Digital Inhaler Discontinuations: Not Enough Uptake of Device
On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.
“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
Digital App Companion to Inhaler
The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.
Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.
When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
Possibility for Objective Data
“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.
“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
CONNECT2: Better Asthma Control at 24 Weeks
Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.
Lack of Inhaler Uptake
“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”
Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”
The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.
On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.
“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
Digital App Companion to Inhaler
The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.
Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.
When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
Possibility for Objective Data
“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.
“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
CONNECT2: Better Asthma Control at 24 Weeks
Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.
Lack of Inhaler Uptake
“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”
Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”
The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.
On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.
“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
Digital App Companion to Inhaler
The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.
Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.
When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
Possibility for Objective Data
“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.
“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
CONNECT2: Better Asthma Control at 24 Weeks
Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.
Lack of Inhaler Uptake
“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”
Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”
The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.
Will Changing the Term Obesity Reduce Stigma?
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Probiotics Emerge as Promising Intervention in Cirrhosis
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
Energy-Restricted Diet Twice Weekly Tops Exercise in T2D
TOPLINE:
Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).
METHODOLOGY:
- Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
- Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
- The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
- The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
- The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.
TAKEAWAY:
- Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
- The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
- Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
- However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.
IN PRACTICE:
“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.”
SOURCE:
Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.
LIMITATIONS:
Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.
DISCLOSURES:
This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).
METHODOLOGY:
- Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
- Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
- The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
- The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
- The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.
TAKEAWAY:
- Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
- The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
- Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
- However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.
IN PRACTICE:
“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.”
SOURCE:
Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.
LIMITATIONS:
Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.
DISCLOSURES:
This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).
METHODOLOGY:
- Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
- Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
- The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
- The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
- The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.
TAKEAWAY:
- Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
- The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
- Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
- However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.
IN PRACTICE:
“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.”
SOURCE:
Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.
LIMITATIONS:
Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.
DISCLOSURES:
This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
New Genetic Variant May Guard Against Alzheimer’s in High-Risk Individuals
, new research suggests.
The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.
While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.
The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.
“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.
The findings were published online in Acta Neuropathologica,
Combing Genetic Data
To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.
They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.
After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.
The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).
The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.
“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.
Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.
The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.
A version of this article appeared on Medscape.com.
, new research suggests.
The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.
While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.
The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.
“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.
The findings were published online in Acta Neuropathologica,
Combing Genetic Data
To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.
They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.
After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.
The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).
The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.
“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.
Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.
The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.
A version of this article appeared on Medscape.com.
, new research suggests.
The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.
While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.
The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.
“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.
The findings were published online in Acta Neuropathologica,
Combing Genetic Data
To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.
They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.
After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.
The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).
The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.
“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.
Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.
The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.
A version of this article appeared on Medscape.com.
FROM ACTA NEUROPATHOLOGICA