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AI Surpasses Harvard Docs on Clinical Reasoning Test
TOPLINE:
The AI had more instances of incorrect reasoning than the doctors did but scored better overall.
METHODOLOGY:
- The study involved 39 physicians from two academic medical centers in Boston and the generative AI model GPT-4.
- Participants were presented with 20 simulated clinical cases involving common problems such as pharyngitis, headache, abdominal pain, cough, and chest pain. Each case included sections describing the triage presentation, review of systems, physical examination, and diagnostic testing.
- The primary outcome was the Revised-IDEA (R-IDEA) score, a 10-point scale evaluating clinical reasoning documentation across four domains: Interpretive summary, differential diagnosis, explanation of the lead diagnosis, and alternative diagnoses.
TAKEAWAY:
- AI achieved a median R-IDEA score of 10, higher than attending physicians (median score, 9) and residents (8).
- The chatbot had a significantly higher estimated probability of achieving a high R-IDEA score of 8-10 (0.99) compared with attendings (0.76) and residents (0.56).
- AI provided more responses that contained instances of incorrect clinical reasoning (13.8%) than residents (2.8%) and attending physicians (12.5%). It performed similarly to physicians in diagnostic accuracy and inclusion of cannot-miss diagnoses.
IN PRACTICE:
“Future research should assess clinical reasoning of the LLM-physician interaction, as LLMs will more likely augment, not replace, the human reasoning process,” the authors of the study wrote.
SOURCE:
Adam Rodman, MD, MPH, with Beth Israel Deaconess Medical Center, Boston, was the corresponding author on the paper. The research was published online in JAMA Internal Medicine.
LIMITATIONS:
Simulated clinical cases may not replicate performance in real-world scenarios. Further training could enhance the performance of the AI, so the study may underestimate its capabilities, the researchers noted.
DISCLOSURES:
The study was supported by the Harvard Clinical and Translational Science Center and Harvard University. Authors disclosed financial ties to publishing companies and Solera Health. Dr. Rodman received funding from the Gordon and Betty Moore Foundation.
This article was created 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.
TOPLINE:
The AI had more instances of incorrect reasoning than the doctors did but scored better overall.
METHODOLOGY:
- The study involved 39 physicians from two academic medical centers in Boston and the generative AI model GPT-4.
- Participants were presented with 20 simulated clinical cases involving common problems such as pharyngitis, headache, abdominal pain, cough, and chest pain. Each case included sections describing the triage presentation, review of systems, physical examination, and diagnostic testing.
- The primary outcome was the Revised-IDEA (R-IDEA) score, a 10-point scale evaluating clinical reasoning documentation across four domains: Interpretive summary, differential diagnosis, explanation of the lead diagnosis, and alternative diagnoses.
TAKEAWAY:
- AI achieved a median R-IDEA score of 10, higher than attending physicians (median score, 9) and residents (8).
- The chatbot had a significantly higher estimated probability of achieving a high R-IDEA score of 8-10 (0.99) compared with attendings (0.76) and residents (0.56).
- AI provided more responses that contained instances of incorrect clinical reasoning (13.8%) than residents (2.8%) and attending physicians (12.5%). It performed similarly to physicians in diagnostic accuracy and inclusion of cannot-miss diagnoses.
IN PRACTICE:
“Future research should assess clinical reasoning of the LLM-physician interaction, as LLMs will more likely augment, not replace, the human reasoning process,” the authors of the study wrote.
SOURCE:
Adam Rodman, MD, MPH, with Beth Israel Deaconess Medical Center, Boston, was the corresponding author on the paper. The research was published online in JAMA Internal Medicine.
LIMITATIONS:
Simulated clinical cases may not replicate performance in real-world scenarios. Further training could enhance the performance of the AI, so the study may underestimate its capabilities, the researchers noted.
DISCLOSURES:
The study was supported by the Harvard Clinical and Translational Science Center and Harvard University. Authors disclosed financial ties to publishing companies and Solera Health. Dr. Rodman received funding from the Gordon and Betty Moore Foundation.
This article was created 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.
TOPLINE:
The AI had more instances of incorrect reasoning than the doctors did but scored better overall.
METHODOLOGY:
- The study involved 39 physicians from two academic medical centers in Boston and the generative AI model GPT-4.
- Participants were presented with 20 simulated clinical cases involving common problems such as pharyngitis, headache, abdominal pain, cough, and chest pain. Each case included sections describing the triage presentation, review of systems, physical examination, and diagnostic testing.
- The primary outcome was the Revised-IDEA (R-IDEA) score, a 10-point scale evaluating clinical reasoning documentation across four domains: Interpretive summary, differential diagnosis, explanation of the lead diagnosis, and alternative diagnoses.
TAKEAWAY:
- AI achieved a median R-IDEA score of 10, higher than attending physicians (median score, 9) and residents (8).
- The chatbot had a significantly higher estimated probability of achieving a high R-IDEA score of 8-10 (0.99) compared with attendings (0.76) and residents (0.56).
- AI provided more responses that contained instances of incorrect clinical reasoning (13.8%) than residents (2.8%) and attending physicians (12.5%). It performed similarly to physicians in diagnostic accuracy and inclusion of cannot-miss diagnoses.
IN PRACTICE:
“Future research should assess clinical reasoning of the LLM-physician interaction, as LLMs will more likely augment, not replace, the human reasoning process,” the authors of the study wrote.
SOURCE:
Adam Rodman, MD, MPH, with Beth Israel Deaconess Medical Center, Boston, was the corresponding author on the paper. The research was published online in JAMA Internal Medicine.
LIMITATIONS:
Simulated clinical cases may not replicate performance in real-world scenarios. Further training could enhance the performance of the AI, so the study may underestimate its capabilities, the researchers noted.
DISCLOSURES:
The study was supported by the Harvard Clinical and Translational Science Center and Harvard University. Authors disclosed financial ties to publishing companies and Solera Health. Dr. Rodman received funding from the Gordon and Betty Moore Foundation.
This article was created 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.
BPH Trial Finds One Approach Clinically Superior
A head-to-head trial of minimally invasive procedures to manage benign prostatic hyperplasia found that urethral implants appear to provide more durable control of symptoms than thermal therapy.
The ongoing CLEAR RCT study includes 68 men in the United States and the United Kingdom who have undergone one of two minimally invasive surgical techniques (MISTs). It found a procedure in which prostate tissue is lifted away from the urethra to improve urinary flow provided faster relief of symptoms, lower rates of catheterization, and higher patient satisfaction at 1 month than did an alternative approach that relies on thermal energy for tissue ablation, according to Mark Rochester, MD, a consultant urologist at the Norfolk and Norwich University Hospitals in England.
“These results give clinicians and patients some data with which to choose between devices,” said Dr. Rochester, who presented the data at the 2024 annual meeting of the European Association of Urology.
CLEAR RCT Called First MIST Controlled Trial
Dr. Rochester called CLEAR RCT “the first head-to-head randomized controlled trial to compare two contemporary MISTs”: UroLift (Teleflex), known generically as a prostatic urethral lift (PUL), and Rezum (Boston Scientific), known as water vapor thermal therapy (WVTT).
In the WVTT technique, thermal energy in the form of water vapor is introduced into the enlarged prostate tissue where it disperses through the interstices to produce denaturization of the tissue and cell death. Over time, the ablated tissue, which is eventually reabsorbed in the healing process, relieves pressure on the urethra to improve passage of urine.
Both procedures can be performed on an outpatient basis without general anesthesia. Each typically permits discontinuation of medications commonly prescribed for lower urinary tract symptoms, and both are associated with a low risk of erectile dysfunction. Most routine activities can be resumed within a few days.
Baseline characteristics of the 35 patients randomized to PUL and 33 patients randomized to WVTT were similar in regard to body mass index, prostate volume, baseline International Prostate Symptom Score (IPSS), post-void volume test, and maximum urinary flow.
Although this is a preliminary 3-month analysis of a study not yet completed, the primary endpoint was catheter independence on postop day 3 through 7. No patients randomized to PUL failed the primary endpoint versus nine (26%) of the patients randomized to WVTT.
Of the nine, six failed because they were not catheter-independent by day 3; three more failed after they had initially achieved catheter independence but then required the device in order to void within 7 days, Dr. Rochester reported. Four of these patients had further recurrences within 3 months of the procedure.
The response measured by symptoms and objective studies of such variables as peak flow (Qmax) also favored PUL over WVTT in the early postperative period, according to the analysis. By 14 days, for example, IPSS scores were superior at 14 days and 1 month, although they no longer differed statistically at the 3-month mark. Qmax was significantly greater in the PUL group at 14 days but not at 1 or 3 months, according to Dr. Rochester.
QOL Advantage at 1 Month Lost at 3 Months
From baseline, more patients in the PUL than WVTT group had a meaningful improvement in quality of life (QoL) at 14 days (39.5% vs 5.6%) and 1 month (47.8% vs 19.2%), Dr. Rochester said. Again, however, the between-group differences had lost significance by 3 months.
Patients who were satisfied or very satisfied at 1 month (48% vs 25%) also favored PUL, and about the same proportion (55%) were satisfied at 3 months, Dr. Rochester said.
Adverse events attributed to these procedures were slightly higher in the PUL group (21%) than the WVTT group (17%), but none was serious. At longest follow-up to date, which is 1 year in some patients, one man in each group required an invasive retreatment.
Patients or clinicians might prefer one technique over the other in an individual case, but the goal of CLEAR RCT was to provide objective evidence when educating patients about treatment options.
“Patients typically want to know which one is preferred, and we needed data to back up this conversation,” Dr. Rochester said.
Measuring the Right Endpoint?
While longer follow-up might reveal differences in the durability of symptom relief, outcomes other than the primary endpoint of CLEAR RCT should be considered when selecting between these modalities, according to Dean Elterman, MD, MSc, an associate professor in urology at the University of Toronto in Canada. He suggested that catheter-free rates on days 3-7 is “a unique primary endpoint.”
“Patients choose different therapies for different personal reasons. For some, having a catheter for less time is an important short-term goal, while for others the long-term benefit may carry more weight,” said Dr. Elterman, who led a study in 2021 that pooled data from two sham-controlled trials to consider differences between PUL and WVTT at 3 years. In that study, WVTT was associated with fewer surgical retreatments (4.4% vs 10.7%) and better symptom relief at long-term follow-up.
Given the differences in the mechanisms of PUL and WVTT, he said it is probably inappropriate to consider just one endpoint, such as early catheter independence, in considering the differences between the two MISTs.
“This study does show PUL patients have less interference with participation in daily activities within the first month, but the clinical improvement and quality of life are the same in each group at 3 months,” he noted.
“If short-term benefits are weighed as more important to a patient, then this study may be informative,” he said. But he thinks many patients will be at least as interested in long-term follow-up to see if early benefits are durable.
Dr. Rochester reported financial relationships with Intuitive Surgical and Teleflex, which manufactures UroLift and was the sponsor of the CLEAR RCT trial. Dr. Elterman reported financial relationships with BioRobotics and Olympus.
A version of this article appeared on Medscape.com.
A head-to-head trial of minimally invasive procedures to manage benign prostatic hyperplasia found that urethral implants appear to provide more durable control of symptoms than thermal therapy.
The ongoing CLEAR RCT study includes 68 men in the United States and the United Kingdom who have undergone one of two minimally invasive surgical techniques (MISTs). It found a procedure in which prostate tissue is lifted away from the urethra to improve urinary flow provided faster relief of symptoms, lower rates of catheterization, and higher patient satisfaction at 1 month than did an alternative approach that relies on thermal energy for tissue ablation, according to Mark Rochester, MD, a consultant urologist at the Norfolk and Norwich University Hospitals in England.
“These results give clinicians and patients some data with which to choose between devices,” said Dr. Rochester, who presented the data at the 2024 annual meeting of the European Association of Urology.
CLEAR RCT Called First MIST Controlled Trial
Dr. Rochester called CLEAR RCT “the first head-to-head randomized controlled trial to compare two contemporary MISTs”: UroLift (Teleflex), known generically as a prostatic urethral lift (PUL), and Rezum (Boston Scientific), known as water vapor thermal therapy (WVTT).
In the WVTT technique, thermal energy in the form of water vapor is introduced into the enlarged prostate tissue where it disperses through the interstices to produce denaturization of the tissue and cell death. Over time, the ablated tissue, which is eventually reabsorbed in the healing process, relieves pressure on the urethra to improve passage of urine.
Both procedures can be performed on an outpatient basis without general anesthesia. Each typically permits discontinuation of medications commonly prescribed for lower urinary tract symptoms, and both are associated with a low risk of erectile dysfunction. Most routine activities can be resumed within a few days.
Baseline characteristics of the 35 patients randomized to PUL and 33 patients randomized to WVTT were similar in regard to body mass index, prostate volume, baseline International Prostate Symptom Score (IPSS), post-void volume test, and maximum urinary flow.
Although this is a preliminary 3-month analysis of a study not yet completed, the primary endpoint was catheter independence on postop day 3 through 7. No patients randomized to PUL failed the primary endpoint versus nine (26%) of the patients randomized to WVTT.
Of the nine, six failed because they were not catheter-independent by day 3; three more failed after they had initially achieved catheter independence but then required the device in order to void within 7 days, Dr. Rochester reported. Four of these patients had further recurrences within 3 months of the procedure.
The response measured by symptoms and objective studies of such variables as peak flow (Qmax) also favored PUL over WVTT in the early postperative period, according to the analysis. By 14 days, for example, IPSS scores were superior at 14 days and 1 month, although they no longer differed statistically at the 3-month mark. Qmax was significantly greater in the PUL group at 14 days but not at 1 or 3 months, according to Dr. Rochester.
QOL Advantage at 1 Month Lost at 3 Months
From baseline, more patients in the PUL than WVTT group had a meaningful improvement in quality of life (QoL) at 14 days (39.5% vs 5.6%) and 1 month (47.8% vs 19.2%), Dr. Rochester said. Again, however, the between-group differences had lost significance by 3 months.
Patients who were satisfied or very satisfied at 1 month (48% vs 25%) also favored PUL, and about the same proportion (55%) were satisfied at 3 months, Dr. Rochester said.
Adverse events attributed to these procedures were slightly higher in the PUL group (21%) than the WVTT group (17%), but none was serious. At longest follow-up to date, which is 1 year in some patients, one man in each group required an invasive retreatment.
Patients or clinicians might prefer one technique over the other in an individual case, but the goal of CLEAR RCT was to provide objective evidence when educating patients about treatment options.
“Patients typically want to know which one is preferred, and we needed data to back up this conversation,” Dr. Rochester said.
Measuring the Right Endpoint?
While longer follow-up might reveal differences in the durability of symptom relief, outcomes other than the primary endpoint of CLEAR RCT should be considered when selecting between these modalities, according to Dean Elterman, MD, MSc, an associate professor in urology at the University of Toronto in Canada. He suggested that catheter-free rates on days 3-7 is “a unique primary endpoint.”
“Patients choose different therapies for different personal reasons. For some, having a catheter for less time is an important short-term goal, while for others the long-term benefit may carry more weight,” said Dr. Elterman, who led a study in 2021 that pooled data from two sham-controlled trials to consider differences between PUL and WVTT at 3 years. In that study, WVTT was associated with fewer surgical retreatments (4.4% vs 10.7%) and better symptom relief at long-term follow-up.
Given the differences in the mechanisms of PUL and WVTT, he said it is probably inappropriate to consider just one endpoint, such as early catheter independence, in considering the differences between the two MISTs.
“This study does show PUL patients have less interference with participation in daily activities within the first month, but the clinical improvement and quality of life are the same in each group at 3 months,” he noted.
“If short-term benefits are weighed as more important to a patient, then this study may be informative,” he said. But he thinks many patients will be at least as interested in long-term follow-up to see if early benefits are durable.
Dr. Rochester reported financial relationships with Intuitive Surgical and Teleflex, which manufactures UroLift and was the sponsor of the CLEAR RCT trial. Dr. Elterman reported financial relationships with BioRobotics and Olympus.
A version of this article appeared on Medscape.com.
A head-to-head trial of minimally invasive procedures to manage benign prostatic hyperplasia found that urethral implants appear to provide more durable control of symptoms than thermal therapy.
The ongoing CLEAR RCT study includes 68 men in the United States and the United Kingdom who have undergone one of two minimally invasive surgical techniques (MISTs). It found a procedure in which prostate tissue is lifted away from the urethra to improve urinary flow provided faster relief of symptoms, lower rates of catheterization, and higher patient satisfaction at 1 month than did an alternative approach that relies on thermal energy for tissue ablation, according to Mark Rochester, MD, a consultant urologist at the Norfolk and Norwich University Hospitals in England.
“These results give clinicians and patients some data with which to choose between devices,” said Dr. Rochester, who presented the data at the 2024 annual meeting of the European Association of Urology.
CLEAR RCT Called First MIST Controlled Trial
Dr. Rochester called CLEAR RCT “the first head-to-head randomized controlled trial to compare two contemporary MISTs”: UroLift (Teleflex), known generically as a prostatic urethral lift (PUL), and Rezum (Boston Scientific), known as water vapor thermal therapy (WVTT).
In the WVTT technique, thermal energy in the form of water vapor is introduced into the enlarged prostate tissue where it disperses through the interstices to produce denaturization of the tissue and cell death. Over time, the ablated tissue, which is eventually reabsorbed in the healing process, relieves pressure on the urethra to improve passage of urine.
Both procedures can be performed on an outpatient basis without general anesthesia. Each typically permits discontinuation of medications commonly prescribed for lower urinary tract symptoms, and both are associated with a low risk of erectile dysfunction. Most routine activities can be resumed within a few days.
Baseline characteristics of the 35 patients randomized to PUL and 33 patients randomized to WVTT were similar in regard to body mass index, prostate volume, baseline International Prostate Symptom Score (IPSS), post-void volume test, and maximum urinary flow.
Although this is a preliminary 3-month analysis of a study not yet completed, the primary endpoint was catheter independence on postop day 3 through 7. No patients randomized to PUL failed the primary endpoint versus nine (26%) of the patients randomized to WVTT.
Of the nine, six failed because they were not catheter-independent by day 3; three more failed after they had initially achieved catheter independence but then required the device in order to void within 7 days, Dr. Rochester reported. Four of these patients had further recurrences within 3 months of the procedure.
The response measured by symptoms and objective studies of such variables as peak flow (Qmax) also favored PUL over WVTT in the early postperative period, according to the analysis. By 14 days, for example, IPSS scores were superior at 14 days and 1 month, although they no longer differed statistically at the 3-month mark. Qmax was significantly greater in the PUL group at 14 days but not at 1 or 3 months, according to Dr. Rochester.
QOL Advantage at 1 Month Lost at 3 Months
From baseline, more patients in the PUL than WVTT group had a meaningful improvement in quality of life (QoL) at 14 days (39.5% vs 5.6%) and 1 month (47.8% vs 19.2%), Dr. Rochester said. Again, however, the between-group differences had lost significance by 3 months.
Patients who were satisfied or very satisfied at 1 month (48% vs 25%) also favored PUL, and about the same proportion (55%) were satisfied at 3 months, Dr. Rochester said.
Adverse events attributed to these procedures were slightly higher in the PUL group (21%) than the WVTT group (17%), but none was serious. At longest follow-up to date, which is 1 year in some patients, one man in each group required an invasive retreatment.
Patients or clinicians might prefer one technique over the other in an individual case, but the goal of CLEAR RCT was to provide objective evidence when educating patients about treatment options.
“Patients typically want to know which one is preferred, and we needed data to back up this conversation,” Dr. Rochester said.
Measuring the Right Endpoint?
While longer follow-up might reveal differences in the durability of symptom relief, outcomes other than the primary endpoint of CLEAR RCT should be considered when selecting between these modalities, according to Dean Elterman, MD, MSc, an associate professor in urology at the University of Toronto in Canada. He suggested that catheter-free rates on days 3-7 is “a unique primary endpoint.”
“Patients choose different therapies for different personal reasons. For some, having a catheter for less time is an important short-term goal, while for others the long-term benefit may carry more weight,” said Dr. Elterman, who led a study in 2021 that pooled data from two sham-controlled trials to consider differences between PUL and WVTT at 3 years. In that study, WVTT was associated with fewer surgical retreatments (4.4% vs 10.7%) and better symptom relief at long-term follow-up.
Given the differences in the mechanisms of PUL and WVTT, he said it is probably inappropriate to consider just one endpoint, such as early catheter independence, in considering the differences between the two MISTs.
“This study does show PUL patients have less interference with participation in daily activities within the first month, but the clinical improvement and quality of life are the same in each group at 3 months,” he noted.
“If short-term benefits are weighed as more important to a patient, then this study may be informative,” he said. But he thinks many patients will be at least as interested in long-term follow-up to see if early benefits are durable.
Dr. Rochester reported financial relationships with Intuitive Surgical and Teleflex, which manufactures UroLift and was the sponsor of the CLEAR RCT trial. Dr. Elterman reported financial relationships with BioRobotics and Olympus.
A version of this article appeared on Medscape.com.
Novel PCSK9 Inhibitor Reduced LDL by 50%
Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.
Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.
“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.
The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
Additional Therapy Needed
The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.
Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.
Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”
LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.
The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).
Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.
The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.
The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).
Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
Rule of Thumb
“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”
All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”
As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets.
The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.
Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).
Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).
A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.
The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
Still Work to Do
During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”
He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”
Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”
That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.
Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.
The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).
A version of this article appeared on Medscape.com.
Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.
Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.
“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.
The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
Additional Therapy Needed
The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.
Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.
Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”
LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.
The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).
Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.
The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.
The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).
Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
Rule of Thumb
“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”
All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”
As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets.
The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.
Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).
Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).
A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.
The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
Still Work to Do
During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”
He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”
Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”
That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.
Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.
The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).
A version of this article appeared on Medscape.com.
Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.
Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.
“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.
The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
Additional Therapy Needed
The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.
Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.
Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”
LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.
The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).
Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.
The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.
The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).
Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
Rule of Thumb
“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”
All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”
As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets.
The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.
Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).
Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).
A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.
The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
Still Work to Do
During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”
He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”
Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”
That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.
Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.
The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).
A version of this article appeared on Medscape.com.
FROM ACC 2024
Pediatric Patients With MS May Do Best on High-Efficacy DMTs
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
FROM AAN 2024
Which Probiotics Are Effective in Irritable Bowel Syndrome?
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French 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.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French 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.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French 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.
How Does Moderate to Severe Eczema Affect Growth in Children?
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
Childhood Loneliness Predictive of Subsequent Psychosis?
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
First Consensus Statement on Improving Healthcare for Children with Neurodevelopmental Disabilities
The statement was published in Pediatrics.
The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.
Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
‘Accessible, Humane, Effective Care’
“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.
The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
Asking the Patient ‘What do You Need?’
One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”
Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
Examples of ‘Ableism’
The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.
The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.
Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.
The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.
But there are personal reasons as well for the team who developed the statement.
“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “
Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”
This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.
The statement was published in Pediatrics.
The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.
Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
‘Accessible, Humane, Effective Care’
“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.
The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
Asking the Patient ‘What do You Need?’
One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”
Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
Examples of ‘Ableism’
The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.
The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.
Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.
The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.
But there are personal reasons as well for the team who developed the statement.
“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “
Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”
This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.
The statement was published in Pediatrics.
The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.
Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
‘Accessible, Humane, Effective Care’
“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.
The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
Asking the Patient ‘What do You Need?’
One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”
Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
Examples of ‘Ableism’
The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.
The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.
Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.
The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.
But there are personal reasons as well for the team who developed the statement.
“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “
Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”
This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.
Time to Lung Disease in Patients With Dermatomyositis Subtype Estimated
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
Botulinum Toxin, Dermal Fillers Safe in Skin of Color Patients, Review Finds
TOPLINE:
, and more data on Black and Latinx populations are needed, according to a literature review.
METHODOLOGY:
- Understanding the efficacy and safety of cosmetic injectables in diverse skin types is important because individuals identifying as racial and ethnic minorities accounted for 18% of neuromodulator procedures and 22% of soft tissue augmentation procedures in 2020 in the United States.
- Researchers reviewed available literature on the usability and efficacy of neuromodulators and soft tissue augmentation in individuals with SOC because of the limited data available in these populations, particularly non-Asian, SOC populations.
- Overall, 88 studies in English were included, which were either dedicated to discussing safety and/or efficacy of injectables in SOC populations or enrolled more than 20% of participants from SOC populations.
- High-quality level I and II evidence was found in 50 studies, and 9940 patients were analyzed in this review.
TAKEAWAY:
- Studies considered high quality indicated that botulinum toxin is safe and effective for treating glabellar lines in Asians; tailored guidelines recommended specific strategies; and adverse events, such as eyelid issues, were more common in Asians.
- Hyaluronic acid fillers showed significant improvement in moderate to severe cases of nasolabial folds in Asians, and adverse effects like swelling and pain were mild to moderate — some cases of granuloma formation and vascular compromise have been reported.
- In Black individuals, botulinum toxin was well tolerated; hyaluronic acid fillers showed favorable safety, with mild to moderate adverse events; and measures like slower injections and subdermal techniques minimized risks.
- In Latinx populations, there was a lack of robust study data on safety and efficacy of botulinum toxin, whereas hyaluronic acid and poly-L-lactic acid fillers were well tolerated.
IN PRACTICE:
“Neuromodulators and dermal fillers are useful and safe as cosmetic and antiaging treatments in SOC populations, with the greatest amount of data supporting its use in Asian populations,” although more data on Black and Latinx populations are needed, the authors concluded. “During cosmetic consultations, physicians should consider the impact of different cultural beauty norms on the aesthetic goals of diverse patient populations,” they added.
SOURCE:
This study led by Shanice McKenzie, MD, from the Department of Dermatology, University of Southern California, Los Angeles, California, was published online in the Journal of Cosmetic Dermatology.
LIMITATIONS:
Most of the recent data and formal consensus guidelines on injectables in the review came from Asian countries, and there was “a relative paucity of research on Black and Latinx populations,” the authors noted.
DISCLOSURES:
The study did not receive any funding. Two authors declared serving as a consultant, investigator, and/or speaker for various companies; the rest had no disclosures to report.
A version of this article appeared on Medscape.com.
TOPLINE:
, and more data on Black and Latinx populations are needed, according to a literature review.
METHODOLOGY:
- Understanding the efficacy and safety of cosmetic injectables in diverse skin types is important because individuals identifying as racial and ethnic minorities accounted for 18% of neuromodulator procedures and 22% of soft tissue augmentation procedures in 2020 in the United States.
- Researchers reviewed available literature on the usability and efficacy of neuromodulators and soft tissue augmentation in individuals with SOC because of the limited data available in these populations, particularly non-Asian, SOC populations.
- Overall, 88 studies in English were included, which were either dedicated to discussing safety and/or efficacy of injectables in SOC populations or enrolled more than 20% of participants from SOC populations.
- High-quality level I and II evidence was found in 50 studies, and 9940 patients were analyzed in this review.
TAKEAWAY:
- Studies considered high quality indicated that botulinum toxin is safe and effective for treating glabellar lines in Asians; tailored guidelines recommended specific strategies; and adverse events, such as eyelid issues, were more common in Asians.
- Hyaluronic acid fillers showed significant improvement in moderate to severe cases of nasolabial folds in Asians, and adverse effects like swelling and pain were mild to moderate — some cases of granuloma formation and vascular compromise have been reported.
- In Black individuals, botulinum toxin was well tolerated; hyaluronic acid fillers showed favorable safety, with mild to moderate adverse events; and measures like slower injections and subdermal techniques minimized risks.
- In Latinx populations, there was a lack of robust study data on safety and efficacy of botulinum toxin, whereas hyaluronic acid and poly-L-lactic acid fillers were well tolerated.
IN PRACTICE:
“Neuromodulators and dermal fillers are useful and safe as cosmetic and antiaging treatments in SOC populations, with the greatest amount of data supporting its use in Asian populations,” although more data on Black and Latinx populations are needed, the authors concluded. “During cosmetic consultations, physicians should consider the impact of different cultural beauty norms on the aesthetic goals of diverse patient populations,” they added.
SOURCE:
This study led by Shanice McKenzie, MD, from the Department of Dermatology, University of Southern California, Los Angeles, California, was published online in the Journal of Cosmetic Dermatology.
LIMITATIONS:
Most of the recent data and formal consensus guidelines on injectables in the review came from Asian countries, and there was “a relative paucity of research on Black and Latinx populations,” the authors noted.
DISCLOSURES:
The study did not receive any funding. Two authors declared serving as a consultant, investigator, and/or speaker for various companies; the rest had no disclosures to report.
A version of this article appeared on Medscape.com.
TOPLINE:
, and more data on Black and Latinx populations are needed, according to a literature review.
METHODOLOGY:
- Understanding the efficacy and safety of cosmetic injectables in diverse skin types is important because individuals identifying as racial and ethnic minorities accounted for 18% of neuromodulator procedures and 22% of soft tissue augmentation procedures in 2020 in the United States.
- Researchers reviewed available literature on the usability and efficacy of neuromodulators and soft tissue augmentation in individuals with SOC because of the limited data available in these populations, particularly non-Asian, SOC populations.
- Overall, 88 studies in English were included, which were either dedicated to discussing safety and/or efficacy of injectables in SOC populations or enrolled more than 20% of participants from SOC populations.
- High-quality level I and II evidence was found in 50 studies, and 9940 patients were analyzed in this review.
TAKEAWAY:
- Studies considered high quality indicated that botulinum toxin is safe and effective for treating glabellar lines in Asians; tailored guidelines recommended specific strategies; and adverse events, such as eyelid issues, were more common in Asians.
- Hyaluronic acid fillers showed significant improvement in moderate to severe cases of nasolabial folds in Asians, and adverse effects like swelling and pain were mild to moderate — some cases of granuloma formation and vascular compromise have been reported.
- In Black individuals, botulinum toxin was well tolerated; hyaluronic acid fillers showed favorable safety, with mild to moderate adverse events; and measures like slower injections and subdermal techniques minimized risks.
- In Latinx populations, there was a lack of robust study data on safety and efficacy of botulinum toxin, whereas hyaluronic acid and poly-L-lactic acid fillers were well tolerated.
IN PRACTICE:
“Neuromodulators and dermal fillers are useful and safe as cosmetic and antiaging treatments in SOC populations, with the greatest amount of data supporting its use in Asian populations,” although more data on Black and Latinx populations are needed, the authors concluded. “During cosmetic consultations, physicians should consider the impact of different cultural beauty norms on the aesthetic goals of diverse patient populations,” they added.
SOURCE:
This study led by Shanice McKenzie, MD, from the Department of Dermatology, University of Southern California, Los Angeles, California, was published online in the Journal of Cosmetic Dermatology.
LIMITATIONS:
Most of the recent data and formal consensus guidelines on injectables in the review came from Asian countries, and there was “a relative paucity of research on Black and Latinx populations,” the authors noted.
DISCLOSURES:
The study did not receive any funding. Two authors declared serving as a consultant, investigator, and/or speaker for various companies; the rest had no disclosures to report.
A version of this article appeared on Medscape.com.