The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.

Respirable crystalline silica, also known as silica dust or quartz dust, is a known carcinogen associated with a range of serious health conditions including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease. 

The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule. 

“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said. 

The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.

In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release. 

Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA. 

“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.

A version of this article appeared on Medscape.com.

The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.

Respirable crystalline silica, also known as silica dust or quartz dust, is a known carcinogen associated with a range of serious health conditions including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease. 

The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule. 

“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said. 

The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.

In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release. 

Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA. 

“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.

A version of this article appeared on Medscape.com.

The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.

Respirable crystalline silica, also known as silica dust or quartz dust, is a known carcinogen associated with a range of serious health conditions including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease. 

The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule. 

“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said. 

The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.

In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release. 

Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA. 

“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.

A version of this article appeared on Medscape.com.

BALTIMORE — Ice packs or topical anesthesia applied to the face before thermomechanical fractional injury therapy to treat wrinkles around the eyes provided satisfactory comfort to the patient during the procedure without sacrificing posttreatment outcomes, a small study of the recently cleared device found.

The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.

“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.

“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”

Dr. Garden

Study Results

The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.

In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.

“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.

The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation. 

Managing Patient Discomfort

Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference. 

“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”

Dr. Lee

A version of this article appeared on Medscape.com.

BALTIMORE — Ice packs or topical anesthesia applied to the face before thermomechanical fractional injury therapy to treat wrinkles around the eyes provided satisfactory comfort to the patient during the procedure without sacrificing posttreatment outcomes, a small study of the recently cleared device found.

The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.

“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.

“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”

Dr. Garden

Study Results

The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.

In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.

“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.

The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation. 

Managing Patient Discomfort

Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference. 

“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”

Dr. Lee

A version of this article appeared on Medscape.com.

BALTIMORE — Ice packs or topical anesthesia applied to the face before thermomechanical fractional injury therapy to treat wrinkles around the eyes provided satisfactory comfort to the patient during the procedure without sacrificing posttreatment outcomes, a small study of the recently cleared device found.

The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.

“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.

“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”

Dr. Garden

Study Results

The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.

In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.

“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.

The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation. 

Managing Patient Discomfort

Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference. 

“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”

Dr. Lee

A version of this article appeared on Medscape.com.

Having two copies of the APOE4 gene may be the genetic cause of up to one fifth of all Alzheimer’s disease cases, a new study suggests.

More than 95% of those with two copies of the gene (APOE4 homozygotes) in a large multicohort study had higher levels of Alzheimer’s disease biomarkers by age 55 years than did those with other APOE gene variants. By age 65 years, most had developed Alzheimer’s disease symptoms and showed abnormal amyloid levels in cerebrospinal fluid and on PET.

Investigators said that such a high penetrance of Alzheimer’s disease pathology in this group suggests that APOE4 may not be just a risk factor for Alzheimer’s disease but also a distinct genetic form of the disease. 

“Sometimes, we say we don’t know the cause of Alzheimer’s disease, but this would be behind 15%-20% of the population of people with Alzheimer’s disease,” lead investigator Juan Fortea, MD, PhD, director of the Memory Unit of the Neurology Department at the Hospital of Sant Pau, Barcelona, Spain, said at a press briefing.

Although some experts urge caution in interpreting these results, investigators and others say the findings, published online in Nature Medicine, could lead to calls for more widespread testing for APOE4 and may spur drug development.
 

High AD Penetrance

Mutations in the APP, PSEN1, and PSEN2 genes are linked to risk for early-onset autosomal-dominant Alzheimer’s disease, and dozens of other genes are associated with greater odds of late-onset disease. Among all these genes, APOE is considered the strongest genetic risk factor for late-onset Alzheimer’s disease. 

Prior studies found that APOE4 homozygotes have a 60% lifetime risk for Alzheimer’s disease by age 85 years, a risk higher than that found with other gene variants or in single APOE carriers or noncarriers. 

Despite that, no previous study had examined the predictability of symptom onset in APOE4 homozygotes, which make up about 2%-3% of the general population and 15-20% of those with Alzheimer’s disease. And because most biomarker studies have combined single- and double-carrier APOE4 carriers into one group, very little was known about the penetrance or disease progression in APOE4 homozygotes.

Investigators analyzed data from 3200 brain donors from the National Alzheimer’s Coordinating Center and more than 10,000 people with Alzheimer’s disease biomarkers from five multicenter cohorts in the United States and Europe.

Nearly all APOE4 homozygotes had either high or intermediate Alzheimer’s disease neuropathologic change scores compared with about 50% among APOE3 homozygotes and was the same regardless of age at time of death. 

Beginning at age 55 years, APOE4 homozygotes exhibited higher levels of abnormal Alzheimer’s disease biomarkers than did APOE3 homozygotes. By age 65 years, nearly everyone with two copies of APOE4 showed abnormal levels of amyloid in cerebrospinal fluid and 75% had positive amyloid scans. 

Other biomarkers showed a biologic penetrance of Alzheimer’s disease that increased with age. By age 80 years, penetrance for all amyloid and tau biomarkers reached 88%. 

Postmortem analysis revealed Alzheimer’s disease and dementia symptoms were evident in APOE4 homozygotes 7-10 years before APOE3 homozygotes, with Alzheimer’s disease symptoms present at age 65 years, minor cognitive impairment at 72 years, dementia at 74 years, and death at 77 years (P <.05 differences).

When they limited analysis to only those who developed Alzheimer’s disease dementia, investigators found no difference in amyloid or tau accumulation between APOE3 and APOE4 homozygotes. That was surprising given the much earlier presentation of clinical symptoms and biomarkers in those who carried two copies of APOE4.
 

More Than a Risk Factor

Overall, study findings provide evidence that APOE4 homozygotes represent another form of genetically determined Alzheimer’s disease, similar to autosomal-dominant Alzheimer’s disease and down syndrome-associated Alzheimer’s disease, investigators said.

“Our work showed that APOE4 homozygotes meet the three main characteristics of genetically determined Alzheimer’s disease, namely near-full penetrance, symptom onset predictability and a predictable sequence of biomarker and clinical changes,” they wrote. 

Based on the results, investigators recommend that future clinical trials avoid combining single and double APOE4 carriers into one study group. 

Because the global average proportion of APOE4 homozygotes is estimated to be approximately 2%, APOE4-homozygous Alzheimer’s disease may represent one of the most frequently occurring Mendelian diseases worldwide. This could have implications for genetic counseling and genetic screening recommendations, they said. 

“We may need to start treating these homozygotes as a separate group in our research so we can really understand the relation between amyloid and tau and symptoms in E4 homozygotes in a way that we have not been able to because of our practice in the field of thinking that APOE4 is this unitary risk effect,” co-investigator Sterling Johnson, PhD, professor of geriatrics and dementia, University of Wisconsin-Madison, said at a press briefing.

The findings may also have implications for Alzheimer’s disease prevention, investigators added.

“What’s particularly important is the promise that perhaps we could treat people before symptoms, particularly in people who already have the disease in their brain such as APOE4 homozygotes, which reliably predicts that they will have impairment and try to treat them beforehand,” co-investigator Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women›s Hospital and Massachusetts General Hospital, Boston, said at a press briefing. 

“This is important for preventing Alzheimer’s-related dementia and a real movement forward in defining the disease on the basis of genetics and biomarkers,” she added. 
 

Experts Offer Mixed Reactions

Commenting on the findings, Paul Mathews, MD, DPhil, group leader of the UK Dementia Research Institute Centre at Imperial College, said that the data point to a need to look at APOE4 differently. 

“One implication of this work is that testing for APOE4 gene homozygosity should be assessed for use clinically, when late middle-aged people present to their doctors with symptoms of dementia,” Dr. Mathews, who was not part of the study, said in a statement. 

In an accompany editorial, Yadong Huang, MD, PhD, Departments of Neurology and Pathology, University of California, San Francisco, and co-authors noted that the findings also have implications for clinical drug trials.

“So far, APOE4 homozygotes have not been treated as a separate predefined treatment group in clinical trials,” they wrote. “Following this study, APOE4 status must be recognized as a crucial parameter in trial design, patient recruitment and data analysis, with APOE4 homozygotes and heterozygotes being clearly separated. Such an approach may enhance the treatment efficacy and help tailor therapeutic interventions more effectively towards genetically defined patient populations.”

Other experts urge caution when interpreting the findings. 

“It is clear that APOE4 homozygosity is tightly linked to the appearance of Alzheimer’s-related pathology, but even at age 80, 12% of people with APOE4/E4 did not have amyloid/tau biomarkers,” said Yuko Hara, PhD, director of aging and Alzheimer’s disease prevention at the Alzheimer’s Drug Discovery Foundation. “Also, having two copies of APOE4 does not mean you will definitely develop symptoms of Alzheimer’s disease in your lifetime,” Dr. Hara added. 

Researchers have long known that APOE4 is a strong risk factor for Alzheimer’s disease and that people with two copies of the gene are at especially high risk, David Curtis, MD, PhD, Genetics Institute at University of College London, England, said in a statement.

“I do not see anything in this paper to justify the claim that carrying two copies of APOE4 represents some ‘distinct genetic form’ of Alzheimer’s disease,” Dr. Curtis said. “No matter how many alleles of APOE4 one carries, the underlying disease processes seem similar across cases of Alzheimer’s disease, suggesting that any effective treatment and prevention strategies, which have yet to be developed would have broad applicability.” 

Study funders included Fondo de Investigaciones Sanitario, Carlos III Health Institute, Fondo Europeo de Desarrollo Regional, Unión Europea, National Institutes of Health, the Department de Salut de la Generalitat de Catalunya, Horizon 2020–Research and Innovation Framework Programme from the European Union, La Caixa Foundation, EIT Digital, and the Alzheimer Association. Dr. Fortea reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Perha, Roche, and outside the submitted work. Dr. Johnson has served at scientific advisory boards for ALZPath, Enigma and Roche Diagnostics. Dr. Sperling has received personal consulting fees from AbbVie, AC Immune, Acumen, Alector, Bristol Myers Squibb, Janssen, Genentech, Ionis and Vaxxinity outside the submitted work. Dr. Huang is a co-founder and scientific advisory board member of GABAeron, Inc. Dr. Mathews reports consultancies with Sudo Biosciences, Nimbus, Redburn. Dr. Hara and Dr. Curtis reported no conflicts. Complete funding sources and disclosures are included in the original articles. 

A version of this article appeared on Medscape.com.

Having two copies of the APOE4 gene may be the genetic cause of up to one fifth of all Alzheimer’s disease cases, a new study suggests.

More than 95% of those with two copies of the gene (APOE4 homozygotes) in a large multicohort study had higher levels of Alzheimer’s disease biomarkers by age 55 years than did those with other APOE gene variants. By age 65 years, most had developed Alzheimer’s disease symptoms and showed abnormal amyloid levels in cerebrospinal fluid and on PET.

Investigators said that such a high penetrance of Alzheimer’s disease pathology in this group suggests that APOE4 may not be just a risk factor for Alzheimer’s disease but also a distinct genetic form of the disease. 

“Sometimes, we say we don’t know the cause of Alzheimer’s disease, but this would be behind 15%-20% of the population of people with Alzheimer’s disease,” lead investigator Juan Fortea, MD, PhD, director of the Memory Unit of the Neurology Department at the Hospital of Sant Pau, Barcelona, Spain, said at a press briefing.

Although some experts urge caution in interpreting these results, investigators and others say the findings, published online in Nature Medicine, could lead to calls for more widespread testing for APOE4 and may spur drug development.
 

High AD Penetrance

Mutations in the APP, PSEN1, and PSEN2 genes are linked to risk for early-onset autosomal-dominant Alzheimer’s disease, and dozens of other genes are associated with greater odds of late-onset disease. Among all these genes, APOE is considered the strongest genetic risk factor for late-onset Alzheimer’s disease. 

Prior studies found that APOE4 homozygotes have a 60% lifetime risk for Alzheimer’s disease by age 85 years, a risk higher than that found with other gene variants or in single APOE carriers or noncarriers. 

Despite that, no previous study had examined the predictability of symptom onset in APOE4 homozygotes, which make up about 2%-3% of the general population and 15-20% of those with Alzheimer’s disease. And because most biomarker studies have combined single- and double-carrier APOE4 carriers into one group, very little was known about the penetrance or disease progression in APOE4 homozygotes.

Investigators analyzed data from 3200 brain donors from the National Alzheimer’s Coordinating Center and more than 10,000 people with Alzheimer’s disease biomarkers from five multicenter cohorts in the United States and Europe.

Nearly all APOE4 homozygotes had either high or intermediate Alzheimer’s disease neuropathologic change scores compared with about 50% among APOE3 homozygotes and was the same regardless of age at time of death. 

Beginning at age 55 years, APOE4 homozygotes exhibited higher levels of abnormal Alzheimer’s disease biomarkers than did APOE3 homozygotes. By age 65 years, nearly everyone with two copies of APOE4 showed abnormal levels of amyloid in cerebrospinal fluid and 75% had positive amyloid scans. 

Other biomarkers showed a biologic penetrance of Alzheimer’s disease that increased with age. By age 80 years, penetrance for all amyloid and tau biomarkers reached 88%. 

Postmortem analysis revealed Alzheimer’s disease and dementia symptoms were evident in APOE4 homozygotes 7-10 years before APOE3 homozygotes, with Alzheimer’s disease symptoms present at age 65 years, minor cognitive impairment at 72 years, dementia at 74 years, and death at 77 years (P <.05 differences).

When they limited analysis to only those who developed Alzheimer’s disease dementia, investigators found no difference in amyloid or tau accumulation between APOE3 and APOE4 homozygotes. That was surprising given the much earlier presentation of clinical symptoms and biomarkers in those who carried two copies of APOE4.
 

More Than a Risk Factor

Overall, study findings provide evidence that APOE4 homozygotes represent another form of genetically determined Alzheimer’s disease, similar to autosomal-dominant Alzheimer’s disease and down syndrome-associated Alzheimer’s disease, investigators said.

“Our work showed that APOE4 homozygotes meet the three main characteristics of genetically determined Alzheimer’s disease, namely near-full penetrance, symptom onset predictability and a predictable sequence of biomarker and clinical changes,” they wrote. 

Based on the results, investigators recommend that future clinical trials avoid combining single and double APOE4 carriers into one study group. 

Because the global average proportion of APOE4 homozygotes is estimated to be approximately 2%, APOE4-homozygous Alzheimer’s disease may represent one of the most frequently occurring Mendelian diseases worldwide. This could have implications for genetic counseling and genetic screening recommendations, they said. 

“We may need to start treating these homozygotes as a separate group in our research so we can really understand the relation between amyloid and tau and symptoms in E4 homozygotes in a way that we have not been able to because of our practice in the field of thinking that APOE4 is this unitary risk effect,” co-investigator Sterling Johnson, PhD, professor of geriatrics and dementia, University of Wisconsin-Madison, said at a press briefing.

The findings may also have implications for Alzheimer’s disease prevention, investigators added.

“What’s particularly important is the promise that perhaps we could treat people before symptoms, particularly in people who already have the disease in their brain such as APOE4 homozygotes, which reliably predicts that they will have impairment and try to treat them beforehand,” co-investigator Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women›s Hospital and Massachusetts General Hospital, Boston, said at a press briefing. 

“This is important for preventing Alzheimer’s-related dementia and a real movement forward in defining the disease on the basis of genetics and biomarkers,” she added. 
 

Experts Offer Mixed Reactions

Commenting on the findings, Paul Mathews, MD, DPhil, group leader of the UK Dementia Research Institute Centre at Imperial College, said that the data point to a need to look at APOE4 differently. 

“One implication of this work is that testing for APOE4 gene homozygosity should be assessed for use clinically, when late middle-aged people present to their doctors with symptoms of dementia,” Dr. Mathews, who was not part of the study, said in a statement. 

In an accompany editorial, Yadong Huang, MD, PhD, Departments of Neurology and Pathology, University of California, San Francisco, and co-authors noted that the findings also have implications for clinical drug trials.

“So far, APOE4 homozygotes have not been treated as a separate predefined treatment group in clinical trials,” they wrote. “Following this study, APOE4 status must be recognized as a crucial parameter in trial design, patient recruitment and data analysis, with APOE4 homozygotes and heterozygotes being clearly separated. Such an approach may enhance the treatment efficacy and help tailor therapeutic interventions more effectively towards genetically defined patient populations.”

Other experts urge caution when interpreting the findings. 

“It is clear that APOE4 homozygosity is tightly linked to the appearance of Alzheimer’s-related pathology, but even at age 80, 12% of people with APOE4/E4 did not have amyloid/tau biomarkers,” said Yuko Hara, PhD, director of aging and Alzheimer’s disease prevention at the Alzheimer’s Drug Discovery Foundation. “Also, having two copies of APOE4 does not mean you will definitely develop symptoms of Alzheimer’s disease in your lifetime,” Dr. Hara added. 

Researchers have long known that APOE4 is a strong risk factor for Alzheimer’s disease and that people with two copies of the gene are at especially high risk, David Curtis, MD, PhD, Genetics Institute at University of College London, England, said in a statement.

“I do not see anything in this paper to justify the claim that carrying two copies of APOE4 represents some ‘distinct genetic form’ of Alzheimer’s disease,” Dr. Curtis said. “No matter how many alleles of APOE4 one carries, the underlying disease processes seem similar across cases of Alzheimer’s disease, suggesting that any effective treatment and prevention strategies, which have yet to be developed would have broad applicability.” 

Study funders included Fondo de Investigaciones Sanitario, Carlos III Health Institute, Fondo Europeo de Desarrollo Regional, Unión Europea, National Institutes of Health, the Department de Salut de la Generalitat de Catalunya, Horizon 2020–Research and Innovation Framework Programme from the European Union, La Caixa Foundation, EIT Digital, and the Alzheimer Association. Dr. Fortea reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Perha, Roche, and outside the submitted work. Dr. Johnson has served at scientific advisory boards for ALZPath, Enigma and Roche Diagnostics. Dr. Sperling has received personal consulting fees from AbbVie, AC Immune, Acumen, Alector, Bristol Myers Squibb, Janssen, Genentech, Ionis and Vaxxinity outside the submitted work. Dr. Huang is a co-founder and scientific advisory board member of GABAeron, Inc. Dr. Mathews reports consultancies with Sudo Biosciences, Nimbus, Redburn. Dr. Hara and Dr. Curtis reported no conflicts. Complete funding sources and disclosures are included in the original articles. 

A version of this article appeared on Medscape.com.

Having two copies of the APOE4 gene may be the genetic cause of up to one fifth of all Alzheimer’s disease cases, a new study suggests.

More than 95% of those with two copies of the gene (APOE4 homozygotes) in a large multicohort study had higher levels of Alzheimer’s disease biomarkers by age 55 years than did those with other APOE gene variants. By age 65 years, most had developed Alzheimer’s disease symptoms and showed abnormal amyloid levels in cerebrospinal fluid and on PET.

Investigators said that such a high penetrance of Alzheimer’s disease pathology in this group suggests that APOE4 may not be just a risk factor for Alzheimer’s disease but also a distinct genetic form of the disease. 

“Sometimes, we say we don’t know the cause of Alzheimer’s disease, but this would be behind 15%-20% of the population of people with Alzheimer’s disease,” lead investigator Juan Fortea, MD, PhD, director of the Memory Unit of the Neurology Department at the Hospital of Sant Pau, Barcelona, Spain, said at a press briefing.

Although some experts urge caution in interpreting these results, investigators and others say the findings, published online in Nature Medicine, could lead to calls for more widespread testing for APOE4 and may spur drug development.
 

High AD Penetrance

Mutations in the APP, PSEN1, and PSEN2 genes are linked to risk for early-onset autosomal-dominant Alzheimer’s disease, and dozens of other genes are associated with greater odds of late-onset disease. Among all these genes, APOE is considered the strongest genetic risk factor for late-onset Alzheimer’s disease. 

Prior studies found that APOE4 homozygotes have a 60% lifetime risk for Alzheimer’s disease by age 85 years, a risk higher than that found with other gene variants or in single APOE carriers or noncarriers. 

Despite that, no previous study had examined the predictability of symptom onset in APOE4 homozygotes, which make up about 2%-3% of the general population and 15-20% of those with Alzheimer’s disease. And because most biomarker studies have combined single- and double-carrier APOE4 carriers into one group, very little was known about the penetrance or disease progression in APOE4 homozygotes.

Investigators analyzed data from 3200 brain donors from the National Alzheimer’s Coordinating Center and more than 10,000 people with Alzheimer’s disease biomarkers from five multicenter cohorts in the United States and Europe.

Nearly all APOE4 homozygotes had either high or intermediate Alzheimer’s disease neuropathologic change scores compared with about 50% among APOE3 homozygotes and was the same regardless of age at time of death. 

Beginning at age 55 years, APOE4 homozygotes exhibited higher levels of abnormal Alzheimer’s disease biomarkers than did APOE3 homozygotes. By age 65 years, nearly everyone with two copies of APOE4 showed abnormal levels of amyloid in cerebrospinal fluid and 75% had positive amyloid scans. 

Other biomarkers showed a biologic penetrance of Alzheimer’s disease that increased with age. By age 80 years, penetrance for all amyloid and tau biomarkers reached 88%. 

Postmortem analysis revealed Alzheimer’s disease and dementia symptoms were evident in APOE4 homozygotes 7-10 years before APOE3 homozygotes, with Alzheimer’s disease symptoms present at age 65 years, minor cognitive impairment at 72 years, dementia at 74 years, and death at 77 years (P <.05 differences).

When they limited analysis to only those who developed Alzheimer’s disease dementia, investigators found no difference in amyloid or tau accumulation between APOE3 and APOE4 homozygotes. That was surprising given the much earlier presentation of clinical symptoms and biomarkers in those who carried two copies of APOE4.
 

More Than a Risk Factor

Overall, study findings provide evidence that APOE4 homozygotes represent another form of genetically determined Alzheimer’s disease, similar to autosomal-dominant Alzheimer’s disease and down syndrome-associated Alzheimer’s disease, investigators said.

“Our work showed that APOE4 homozygotes meet the three main characteristics of genetically determined Alzheimer’s disease, namely near-full penetrance, symptom onset predictability and a predictable sequence of biomarker and clinical changes,” they wrote. 

Based on the results, investigators recommend that future clinical trials avoid combining single and double APOE4 carriers into one study group. 

Because the global average proportion of APOE4 homozygotes is estimated to be approximately 2%, APOE4-homozygous Alzheimer’s disease may represent one of the most frequently occurring Mendelian diseases worldwide. This could have implications for genetic counseling and genetic screening recommendations, they said. 

“We may need to start treating these homozygotes as a separate group in our research so we can really understand the relation between amyloid and tau and symptoms in E4 homozygotes in a way that we have not been able to because of our practice in the field of thinking that APOE4 is this unitary risk effect,” co-investigator Sterling Johnson, PhD, professor of geriatrics and dementia, University of Wisconsin-Madison, said at a press briefing.

The findings may also have implications for Alzheimer’s disease prevention, investigators added.

“What’s particularly important is the promise that perhaps we could treat people before symptoms, particularly in people who already have the disease in their brain such as APOE4 homozygotes, which reliably predicts that they will have impairment and try to treat them beforehand,” co-investigator Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women›s Hospital and Massachusetts General Hospital, Boston, said at a press briefing. 

“This is important for preventing Alzheimer’s-related dementia and a real movement forward in defining the disease on the basis of genetics and biomarkers,” she added. 
 

Experts Offer Mixed Reactions

Commenting on the findings, Paul Mathews, MD, DPhil, group leader of the UK Dementia Research Institute Centre at Imperial College, said that the data point to a need to look at APOE4 differently. 

“One implication of this work is that testing for APOE4 gene homozygosity should be assessed for use clinically, when late middle-aged people present to their doctors with symptoms of dementia,” Dr. Mathews, who was not part of the study, said in a statement. 

In an accompany editorial, Yadong Huang, MD, PhD, Departments of Neurology and Pathology, University of California, San Francisco, and co-authors noted that the findings also have implications for clinical drug trials.

“So far, APOE4 homozygotes have not been treated as a separate predefined treatment group in clinical trials,” they wrote. “Following this study, APOE4 status must be recognized as a crucial parameter in trial design, patient recruitment and data analysis, with APOE4 homozygotes and heterozygotes being clearly separated. Such an approach may enhance the treatment efficacy and help tailor therapeutic interventions more effectively towards genetically defined patient populations.”

Other experts urge caution when interpreting the findings. 

“It is clear that APOE4 homozygosity is tightly linked to the appearance of Alzheimer’s-related pathology, but even at age 80, 12% of people with APOE4/E4 did not have amyloid/tau biomarkers,” said Yuko Hara, PhD, director of aging and Alzheimer’s disease prevention at the Alzheimer’s Drug Discovery Foundation. “Also, having two copies of APOE4 does not mean you will definitely develop symptoms of Alzheimer’s disease in your lifetime,” Dr. Hara added. 

Researchers have long known that APOE4 is a strong risk factor for Alzheimer’s disease and that people with two copies of the gene are at especially high risk, David Curtis, MD, PhD, Genetics Institute at University of College London, England, said in a statement.

“I do not see anything in this paper to justify the claim that carrying two copies of APOE4 represents some ‘distinct genetic form’ of Alzheimer’s disease,” Dr. Curtis said. “No matter how many alleles of APOE4 one carries, the underlying disease processes seem similar across cases of Alzheimer’s disease, suggesting that any effective treatment and prevention strategies, which have yet to be developed would have broad applicability.” 

Study funders included Fondo de Investigaciones Sanitario, Carlos III Health Institute, Fondo Europeo de Desarrollo Regional, Unión Europea, National Institutes of Health, the Department de Salut de la Generalitat de Catalunya, Horizon 2020–Research and Innovation Framework Programme from the European Union, La Caixa Foundation, EIT Digital, and the Alzheimer Association. Dr. Fortea reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Perha, Roche, and outside the submitted work. Dr. Johnson has served at scientific advisory boards for ALZPath, Enigma and Roche Diagnostics. Dr. Sperling has received personal consulting fees from AbbVie, AC Immune, Acumen, Alector, Bristol Myers Squibb, Janssen, Genentech, Ionis and Vaxxinity outside the submitted work. Dr. Huang is a co-founder and scientific advisory board member of GABAeron, Inc. Dr. Mathews reports consultancies with Sudo Biosciences, Nimbus, Redburn. Dr. Hara and Dr. Curtis reported no conflicts. Complete funding sources and disclosures are included in the original articles. 

A version of this article appeared on Medscape.com.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

High olive oil consumption is associated with a significant decreased risk for dementia-related mortality, regardless of overall diet quality, a new study suggested.

Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.

Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.

“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.

However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.

The study was published online in JAMA Network Open.
 

A Spoonful of Olive Oil

A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.

Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.

Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.

The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.

There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.

Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.

Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).

No interaction by diet quality scores was found.
 

No Link With Diet Quality

“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.

Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.

“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”

The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.

It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.

The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
 

Causality Versus Connection

Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.

Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.

Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.

“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.

She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.

It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”

This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

The latest research on therapeutic management of patients with relapsing-remitting multiple sclerosis (RRMS) presented at the American Academy of Neurology (AAN) 2024 annual meeting is reported by Dr Pavan Bhargava from the Johns Hopkins University School of Medicine in Baltimore, Maryland. 

Dr Bhargava first discusses a small study out of Germany exploring child development after exposure to monoclonal antibodies (mAbs) during breastfeeding. Currently, most mAbs are not approved for use during lactation. However, researchers found that infants studied for up to 36 months showed no evidence of adverse development or health effects compared with controls.   

Next, Dr Bhargava discusses a trial examining pregnancy and infant outcomes in patients receiving ocrelizumab. They analyzed registry data of 3000 pregnancies and determined that in-utero exposure to ocrelizumab was not associated with an increased risk for adverse outcomes.  

He then details a small, single-center cohort study evaluating the infection rates associated with anti-CD20 use in pediatric-onset RRMS. The study reported that approximately one third of participants experienced moderate to severe infections over 5 years of follow-up.  

Finally, Dr Bhargava highlights the CHIMES trial, a 1-year analysis of efficacy and safety data from Black and Hispanic persons with RRMS who received ocrelizumab. Researchers found that the overall efficacy and safety results were similar to prior ocrelizumab clinical trials.

--

Pavan Bhargava, MD, Associate Professor, Staff Physician, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 

Pavan Bhargava, MD, has disclosed no relevant financial relationships 

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Biomarkers indicating worsening of progressive multiple sclerosis (MS) can inform decisions about treatment, and two studies presented at the 2024 American Academy of Neurology meeting show promise in this area.

Dr Patricia Coyle of Stony Brook University Hospital in Stony Brook, New York, discusses a study showing that stool glial fibrillary acidic protein (GFAP) was markedly increased in patients with progressive MS vs those with relapsing-remitting disease or healthy controls.

A separate study using brain and cervical spine MRI showed that cervical spine gray matter atrophy, particularly at C2-3, strongly correlated with disability markers in patients with progressive MS.

Dr Coyle closes by outlining a small but important study showing that nasal foralumab dampened microglial activation and stabilized clinical progression in patients with progressive MS.

--

Patricia K. Coyle, MD, Professor and Interim Chair, Department of Neurology; Director, MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, New York 

Patricia K. Coyle, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Accordant; Amgen; Biogen; Bristol Myers Squibb; Eli Lilly & Company; EMD Serono; GSK; Genentech; Horizon; LabCorp; Mylan; Novartis; Sanofi Genzyme; Viatris 

Received research grant from: Celgene; CorEvitas LLC; Genentech/Roche; NINDS; Sanofi Genzyme

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Highlights of the latest research on therapeutic management of patients with myasthenia gravis (MG) presented at the American Academy of Neurology (AAN) 2024 annual meeting are discussed by Dr Richard Nowak of Yale University, New Haven, Connecticut. 

Dr Nowak first discusses LUMINESCE, a phase 3, randomized, double-blind study assessing the efficacy and safety of satralizumab, a humanized interleukin-6 receptor monoclonal recycling antibody. In this trial with 188 participants, satralizumab provided a statistically relevant, though modest, improvement in the Myasthenia Gravis Activities of Daily Living score.  

Next, Dr Nowak details part A of ADAPT NXT, comparing a fixed- cycle dosing vs every-other-week dosing of intravenous efgartigimod. The researchers found that efgartigimod was well tolerated regardless of the regimen used, offering a way to individualize treatment for patients with MG.  

He then discusses the CHAMPION MG open-label extension trial, which examined the long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody–positive generalized MG. The final analysis demonstrated the drug's durable efficacy through 164 weeks in this patient population. 

Finally, Dr Nowak reports on a small trial using retrospective data determining the effectiveness of eculizumab treatment by start time. The study found that early eculizumab initiation in the first 2 years of diagnosis may offer greater clinical benefit compared with later initiation.

--

Richard J. Nowak, MD 

Director, Yale Myasthenia Gravis Clinic, Associate Professor of Neurology; Division of Neuromuscular Medicine, Department of Neurology 

Yale School of Medicine, New Haven, Connecticut

Richard J. Nowak, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a board of directors for: Myasthenia Gravis Foundation of America 

Serve(d) as a consultant for: Alexion; argenx; Amgen; Janssen; Cour; UCB; Immunovant 

Received research grant from: National Institutes of Health; Myasthenia Gravis Foundation of America; Alexion; argenx; Amgen; Janssen; Immunovant; UCB 

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .