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Study Finds Differences in Side Effect Profiles With Two Oral Psoriasis Therapies
TOPLINE:
, according to a retrospective comparison using US Food and Drug Administration (FDA) data.
METHODOLOGY:
- To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
- The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
- AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.
TAKEAWAY:
- There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
- The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
- The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
- Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.
IN PRACTICE:
The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.
SOURCE:
Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.
LIMITATIONS:
The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.
DISCLOSURES:
The study received no funding, and the authors had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a retrospective comparison using US Food and Drug Administration (FDA) data.
METHODOLOGY:
- To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
- The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
- AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.
TAKEAWAY:
- There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
- The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
- The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
- Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.
IN PRACTICE:
The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.
SOURCE:
Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.
LIMITATIONS:
The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.
DISCLOSURES:
The study received no funding, and the authors had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a retrospective comparison using US Food and Drug Administration (FDA) data.
METHODOLOGY:
- To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
- The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
- AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.
TAKEAWAY:
- There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
- The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
- The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
- Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.
IN PRACTICE:
The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.
SOURCE:
Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.
LIMITATIONS:
The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.
DISCLOSURES:
The study received no funding, and the authors had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Risk of MACE Comparable Among Biologic Classes for Psoriasis, PsA
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
Study Links Newer Shingles Vaccine to Delayed Dementia Diagnosis
The study builds on previous observations of a reduction in dementia risk with the older live shingles vaccine and reports a delay in dementia diagnosis of 164 days with the newer recombinant version, compared with the live vaccine.
“Given the prevalence of dementia, a delay of 164 days in diagnosis would not be a trivial effect at the public health level. It’s a big enough effect that if there is a causality it feels meaningful,” said senior author Paul Harrison, DM, FRCPsych, professor of psychiatry at the University of Oxford, Oxford, England.
But Dr. Harrison stressed that the study had not proven that the shingles vaccine reduced dementia risk.
“The design of the study allows us to do away with many of the confounding effects we usually see in observational studies, but this is still an observational study, and as such it cannot prove a definite causal effect,” he said.
The study was published online on July 25 in Nature Medicine.
‘Natural Experiment’
Given the risk for deleterious consequences of shingles, vaccination is now recommended for older adults in many countries. The previously used live shingles vaccine (Zostavax) is being replaced in most countries with the new recombinant shingles vaccine (Shingrix), which is more effective at preventing shingles infection.
The current study made use of a “natural experiment” in the United States, which switched over from use of the live vaccine to the recombinant vaccine in October 2017.
Researchers used electronic heath records to compare the incidence of a dementia diagnosis in individuals who received the live shingles vaccine prior to October 2017 with those who received the recombinant version after the United States made the switch.
They also used propensity score matching to further control for confounding factors, comparing 103,837 individuals who received a first dose of the live shingles vaccine between October 2014 and September 2017 with the same number of matched people who received the recombinant vaccine between November 2017 and October 2020.
Results showed that within the 6 years after vaccination, the recombinant vaccine was associated with a delay in the diagnosis of dementia, compared with the live vaccine. Specifically, receiving the recombinant vaccine was associated with a 17% increase in diagnosis-free time, translating to 164 additional days lived without a diagnosis of dementia in those subsequently affected.
As an additional control, the researchers also found significantly lower risks for dementia in individuals receiving the new recombinant shingles vaccine vs two other vaccines commonly used in older people: influenza and tetanus/diphtheria/pertussis vaccines, with increases in diagnosis-free time of 14%-27%.
Reduced Risk or Delayed Diagnosis?
Speaking at a Science Media Centre press conference on the study, lead author Maxime Taquet, PhD, FRCPsych, clinical lecturer in psychiatry at the University of Oxford, noted that the total number of dementia cases were similar in the two shingles vaccine groups by the end of the 6-year follow-up period but there was a difference in the time at which they received a diagnosis of dementia.
“The study suggests that rather than actually reducing dementia risk, the recombinant vaccine delays the onset of dementia compared to the live vaccine in patients who go on to develop the condition,” he explained.
But when comparing the recombinant vaccine with the influenza and tetanus/diphtheria/pertussis vaccines there was a clear reduction in dementia risk itself, Dr. Taquet reported.
“It might well be that the live vaccine has a potential effect on the risk of dementia itself and therefore the recombinant vaccine only shows a delay in dementia compared to the live vaccine, but both of them might decrease the overall risk of dementia,” he suggested.
But the researchers cautioned that this study could not prove causality.
“While the two groups were very carefully matched in terms of factors that might influence the development of dementia, we still have to be cautious before assuming that the vaccine is indeed causally reducing the risk of onset of dementia,” Dr. Harrison warned.
The researchers say the results would need to be confirmed in a randomized trial, which may have to be conducted in a slightly younger age group, as currently shingles vaccine is recommended for all older individuals in the United Kingdom.
Vaccine recommendations vary from country to country, Dr. Harrison added. In the United States, the Centers for Disease Control and Prevention recommends the recombinant shingles vaccine for all adults aged 50 years or older.
In the meantime, it would be interesting to see whether further observational studies in other countries find similar results as this US study, Dr. Harrison said.
Mechanism Uncertain
Speculating on a possible mechanism behind the findings, Dr. Harrison suggested two plausible explanations.
“First, it is thought that the herpes virus could be one of many factors that could promote dementia, so a vaccine that stops reactivation of this virus might therefore be delaying that process,” he noted.
The other possibility is that adjuvants included in the recombinant vaccine to stimulate the immune system might have played a role.
“We don’t have any data on the mechanism, and thus study did not address that, so further studies are needed to look into this,” Dr. Harrison said.
Stronger Effect in Women
Another intriguing finding is that the association with the recombinant vaccine and delayed dementia diagnosis seemed to be stronger in women vs men.
In the original study of the live shingles vaccine, a protective effect against dementia was shown only in women.
In the current study, the delay in dementia diagnosis was seen in both sexes but was stronger in women, showing a 22% increased time without dementia in women versus a 13% increased time in men with the recombinant versus the live vaccine.
As expected, the recombinant vaccine was associated with a lower risk for shingles disease vs the live vaccine (2.5% versus 3.5%), but women did not have a better response than men did in this respect.
“The better protection against shingles with the recombinant vaccine was similar in men and women, an observation that might be one reason to question the possible mechanism behind the dementia effect being better suppression of the herpes zoster virus by the recombinant vaccine,” Dr. Harrison commented.
Though these findings are not likely to lead to any immediate changes in policy regarding the shingles vaccine, Dr. Harrison said it would be interesting to see whether uptake of the vaccine increased after this study.
He estimated that, currently in the United Kingdom, about 60% of older adults choose to have the shingles vaccine. A 2020 study in the United States found that only about one-third of US adults over 60 had received the vaccine.
“It will be interesting to see if that figure increases after these data are publicized, but I am not recommending that people have the vaccine specifically to lower their risk of dementia because of the caveats about the study that we have discussed,” he commented.
Outside Experts Positive
Outside experts, providing comment to the Science Media Centre, welcomed the new research.
“ The study is very well-conducted and adds to previous data indicating that vaccination against shingles is associated with lower dementia risk. More research is needed in future to determine why this vaccine is associated with lower dementia risk,” said Tara Spires-Jones, FMedSci, president of the British Neuroscience Association.
The high number of patients in the study and the adjustments for potential confounders are also strong points, noted Andrew Doig, PhD, professor of biochemistry, University of Manchester, Manchester, England.
“This is a significant result, comparable in effectiveness to the recent antibody drugs for Alzheimer’s disease,” Dr. Doig said. “Administering the recombinant shingles vaccine could well be a simple and cheap way to lower the risk of Alzheimer’s disease.”
Dr. Doig noted that a link between herpes zoster infection and the onset of dementia has been suspected for some time, and a trial of the antiviral drug valacyclovir against Alzheimer’s disease is currently underway.
In regard to the shingles vaccine, he said a placebo-controlled trial would be needed to prove causality.
“We also need to see how many years the effect might last and whether we should vaccinate people at a younger age. We know that the path to Alzheimer’s can start decades before any symptoms are apparent, so the vaccine might be even more effective if given to people in their 40s or 50s,” he said.
Dr. Harrison and Dr. Taquet reported no disclosures. Dr. Doig is a founder, director, and consultant for PharmaKure, which works on Alzheimer’s drugs and diagnostics. Other commentators declared no disclosures.
A version of this article first appeared on Medscape.com.
The study builds on previous observations of a reduction in dementia risk with the older live shingles vaccine and reports a delay in dementia diagnosis of 164 days with the newer recombinant version, compared with the live vaccine.
“Given the prevalence of dementia, a delay of 164 days in diagnosis would not be a trivial effect at the public health level. It’s a big enough effect that if there is a causality it feels meaningful,” said senior author Paul Harrison, DM, FRCPsych, professor of psychiatry at the University of Oxford, Oxford, England.
But Dr. Harrison stressed that the study had not proven that the shingles vaccine reduced dementia risk.
“The design of the study allows us to do away with many of the confounding effects we usually see in observational studies, but this is still an observational study, and as such it cannot prove a definite causal effect,” he said.
The study was published online on July 25 in Nature Medicine.
‘Natural Experiment’
Given the risk for deleterious consequences of shingles, vaccination is now recommended for older adults in many countries. The previously used live shingles vaccine (Zostavax) is being replaced in most countries with the new recombinant shingles vaccine (Shingrix), which is more effective at preventing shingles infection.
The current study made use of a “natural experiment” in the United States, which switched over from use of the live vaccine to the recombinant vaccine in October 2017.
Researchers used electronic heath records to compare the incidence of a dementia diagnosis in individuals who received the live shingles vaccine prior to October 2017 with those who received the recombinant version after the United States made the switch.
They also used propensity score matching to further control for confounding factors, comparing 103,837 individuals who received a first dose of the live shingles vaccine between October 2014 and September 2017 with the same number of matched people who received the recombinant vaccine between November 2017 and October 2020.
Results showed that within the 6 years after vaccination, the recombinant vaccine was associated with a delay in the diagnosis of dementia, compared with the live vaccine. Specifically, receiving the recombinant vaccine was associated with a 17% increase in diagnosis-free time, translating to 164 additional days lived without a diagnosis of dementia in those subsequently affected.
As an additional control, the researchers also found significantly lower risks for dementia in individuals receiving the new recombinant shingles vaccine vs two other vaccines commonly used in older people: influenza and tetanus/diphtheria/pertussis vaccines, with increases in diagnosis-free time of 14%-27%.
Reduced Risk or Delayed Diagnosis?
Speaking at a Science Media Centre press conference on the study, lead author Maxime Taquet, PhD, FRCPsych, clinical lecturer in psychiatry at the University of Oxford, noted that the total number of dementia cases were similar in the two shingles vaccine groups by the end of the 6-year follow-up period but there was a difference in the time at which they received a diagnosis of dementia.
“The study suggests that rather than actually reducing dementia risk, the recombinant vaccine delays the onset of dementia compared to the live vaccine in patients who go on to develop the condition,” he explained.
But when comparing the recombinant vaccine with the influenza and tetanus/diphtheria/pertussis vaccines there was a clear reduction in dementia risk itself, Dr. Taquet reported.
“It might well be that the live vaccine has a potential effect on the risk of dementia itself and therefore the recombinant vaccine only shows a delay in dementia compared to the live vaccine, but both of them might decrease the overall risk of dementia,” he suggested.
But the researchers cautioned that this study could not prove causality.
“While the two groups were very carefully matched in terms of factors that might influence the development of dementia, we still have to be cautious before assuming that the vaccine is indeed causally reducing the risk of onset of dementia,” Dr. Harrison warned.
The researchers say the results would need to be confirmed in a randomized trial, which may have to be conducted in a slightly younger age group, as currently shingles vaccine is recommended for all older individuals in the United Kingdom.
Vaccine recommendations vary from country to country, Dr. Harrison added. In the United States, the Centers for Disease Control and Prevention recommends the recombinant shingles vaccine for all adults aged 50 years or older.
In the meantime, it would be interesting to see whether further observational studies in other countries find similar results as this US study, Dr. Harrison said.
Mechanism Uncertain
Speculating on a possible mechanism behind the findings, Dr. Harrison suggested two plausible explanations.
“First, it is thought that the herpes virus could be one of many factors that could promote dementia, so a vaccine that stops reactivation of this virus might therefore be delaying that process,” he noted.
The other possibility is that adjuvants included in the recombinant vaccine to stimulate the immune system might have played a role.
“We don’t have any data on the mechanism, and thus study did not address that, so further studies are needed to look into this,” Dr. Harrison said.
Stronger Effect in Women
Another intriguing finding is that the association with the recombinant vaccine and delayed dementia diagnosis seemed to be stronger in women vs men.
In the original study of the live shingles vaccine, a protective effect against dementia was shown only in women.
In the current study, the delay in dementia diagnosis was seen in both sexes but was stronger in women, showing a 22% increased time without dementia in women versus a 13% increased time in men with the recombinant versus the live vaccine.
As expected, the recombinant vaccine was associated with a lower risk for shingles disease vs the live vaccine (2.5% versus 3.5%), but women did not have a better response than men did in this respect.
“The better protection against shingles with the recombinant vaccine was similar in men and women, an observation that might be one reason to question the possible mechanism behind the dementia effect being better suppression of the herpes zoster virus by the recombinant vaccine,” Dr. Harrison commented.
Though these findings are not likely to lead to any immediate changes in policy regarding the shingles vaccine, Dr. Harrison said it would be interesting to see whether uptake of the vaccine increased after this study.
He estimated that, currently in the United Kingdom, about 60% of older adults choose to have the shingles vaccine. A 2020 study in the United States found that only about one-third of US adults over 60 had received the vaccine.
“It will be interesting to see if that figure increases after these data are publicized, but I am not recommending that people have the vaccine specifically to lower their risk of dementia because of the caveats about the study that we have discussed,” he commented.
Outside Experts Positive
Outside experts, providing comment to the Science Media Centre, welcomed the new research.
“ The study is very well-conducted and adds to previous data indicating that vaccination against shingles is associated with lower dementia risk. More research is needed in future to determine why this vaccine is associated with lower dementia risk,” said Tara Spires-Jones, FMedSci, president of the British Neuroscience Association.
The high number of patients in the study and the adjustments for potential confounders are also strong points, noted Andrew Doig, PhD, professor of biochemistry, University of Manchester, Manchester, England.
“This is a significant result, comparable in effectiveness to the recent antibody drugs for Alzheimer’s disease,” Dr. Doig said. “Administering the recombinant shingles vaccine could well be a simple and cheap way to lower the risk of Alzheimer’s disease.”
Dr. Doig noted that a link between herpes zoster infection and the onset of dementia has been suspected for some time, and a trial of the antiviral drug valacyclovir against Alzheimer’s disease is currently underway.
In regard to the shingles vaccine, he said a placebo-controlled trial would be needed to prove causality.
“We also need to see how many years the effect might last and whether we should vaccinate people at a younger age. We know that the path to Alzheimer’s can start decades before any symptoms are apparent, so the vaccine might be even more effective if given to people in their 40s or 50s,” he said.
Dr. Harrison and Dr. Taquet reported no disclosures. Dr. Doig is a founder, director, and consultant for PharmaKure, which works on Alzheimer’s drugs and diagnostics. Other commentators declared no disclosures.
A version of this article first appeared on Medscape.com.
The study builds on previous observations of a reduction in dementia risk with the older live shingles vaccine and reports a delay in dementia diagnosis of 164 days with the newer recombinant version, compared with the live vaccine.
“Given the prevalence of dementia, a delay of 164 days in diagnosis would not be a trivial effect at the public health level. It’s a big enough effect that if there is a causality it feels meaningful,” said senior author Paul Harrison, DM, FRCPsych, professor of psychiatry at the University of Oxford, Oxford, England.
But Dr. Harrison stressed that the study had not proven that the shingles vaccine reduced dementia risk.
“The design of the study allows us to do away with many of the confounding effects we usually see in observational studies, but this is still an observational study, and as such it cannot prove a definite causal effect,” he said.
The study was published online on July 25 in Nature Medicine.
‘Natural Experiment’
Given the risk for deleterious consequences of shingles, vaccination is now recommended for older adults in many countries. The previously used live shingles vaccine (Zostavax) is being replaced in most countries with the new recombinant shingles vaccine (Shingrix), which is more effective at preventing shingles infection.
The current study made use of a “natural experiment” in the United States, which switched over from use of the live vaccine to the recombinant vaccine in October 2017.
Researchers used electronic heath records to compare the incidence of a dementia diagnosis in individuals who received the live shingles vaccine prior to October 2017 with those who received the recombinant version after the United States made the switch.
They also used propensity score matching to further control for confounding factors, comparing 103,837 individuals who received a first dose of the live shingles vaccine between October 2014 and September 2017 with the same number of matched people who received the recombinant vaccine between November 2017 and October 2020.
Results showed that within the 6 years after vaccination, the recombinant vaccine was associated with a delay in the diagnosis of dementia, compared with the live vaccine. Specifically, receiving the recombinant vaccine was associated with a 17% increase in diagnosis-free time, translating to 164 additional days lived without a diagnosis of dementia in those subsequently affected.
As an additional control, the researchers also found significantly lower risks for dementia in individuals receiving the new recombinant shingles vaccine vs two other vaccines commonly used in older people: influenza and tetanus/diphtheria/pertussis vaccines, with increases in diagnosis-free time of 14%-27%.
Reduced Risk or Delayed Diagnosis?
Speaking at a Science Media Centre press conference on the study, lead author Maxime Taquet, PhD, FRCPsych, clinical lecturer in psychiatry at the University of Oxford, noted that the total number of dementia cases were similar in the two shingles vaccine groups by the end of the 6-year follow-up period but there was a difference in the time at which they received a diagnosis of dementia.
“The study suggests that rather than actually reducing dementia risk, the recombinant vaccine delays the onset of dementia compared to the live vaccine in patients who go on to develop the condition,” he explained.
But when comparing the recombinant vaccine with the influenza and tetanus/diphtheria/pertussis vaccines there was a clear reduction in dementia risk itself, Dr. Taquet reported.
“It might well be that the live vaccine has a potential effect on the risk of dementia itself and therefore the recombinant vaccine only shows a delay in dementia compared to the live vaccine, but both of them might decrease the overall risk of dementia,” he suggested.
But the researchers cautioned that this study could not prove causality.
“While the two groups were very carefully matched in terms of factors that might influence the development of dementia, we still have to be cautious before assuming that the vaccine is indeed causally reducing the risk of onset of dementia,” Dr. Harrison warned.
The researchers say the results would need to be confirmed in a randomized trial, which may have to be conducted in a slightly younger age group, as currently shingles vaccine is recommended for all older individuals in the United Kingdom.
Vaccine recommendations vary from country to country, Dr. Harrison added. In the United States, the Centers for Disease Control and Prevention recommends the recombinant shingles vaccine for all adults aged 50 years or older.
In the meantime, it would be interesting to see whether further observational studies in other countries find similar results as this US study, Dr. Harrison said.
Mechanism Uncertain
Speculating on a possible mechanism behind the findings, Dr. Harrison suggested two plausible explanations.
“First, it is thought that the herpes virus could be one of many factors that could promote dementia, so a vaccine that stops reactivation of this virus might therefore be delaying that process,” he noted.
The other possibility is that adjuvants included in the recombinant vaccine to stimulate the immune system might have played a role.
“We don’t have any data on the mechanism, and thus study did not address that, so further studies are needed to look into this,” Dr. Harrison said.
Stronger Effect in Women
Another intriguing finding is that the association with the recombinant vaccine and delayed dementia diagnosis seemed to be stronger in women vs men.
In the original study of the live shingles vaccine, a protective effect against dementia was shown only in women.
In the current study, the delay in dementia diagnosis was seen in both sexes but was stronger in women, showing a 22% increased time without dementia in women versus a 13% increased time in men with the recombinant versus the live vaccine.
As expected, the recombinant vaccine was associated with a lower risk for shingles disease vs the live vaccine (2.5% versus 3.5%), but women did not have a better response than men did in this respect.
“The better protection against shingles with the recombinant vaccine was similar in men and women, an observation that might be one reason to question the possible mechanism behind the dementia effect being better suppression of the herpes zoster virus by the recombinant vaccine,” Dr. Harrison commented.
Though these findings are not likely to lead to any immediate changes in policy regarding the shingles vaccine, Dr. Harrison said it would be interesting to see whether uptake of the vaccine increased after this study.
He estimated that, currently in the United Kingdom, about 60% of older adults choose to have the shingles vaccine. A 2020 study in the United States found that only about one-third of US adults over 60 had received the vaccine.
“It will be interesting to see if that figure increases after these data are publicized, but I am not recommending that people have the vaccine specifically to lower their risk of dementia because of the caveats about the study that we have discussed,” he commented.
Outside Experts Positive
Outside experts, providing comment to the Science Media Centre, welcomed the new research.
“ The study is very well-conducted and adds to previous data indicating that vaccination against shingles is associated with lower dementia risk. More research is needed in future to determine why this vaccine is associated with lower dementia risk,” said Tara Spires-Jones, FMedSci, president of the British Neuroscience Association.
The high number of patients in the study and the adjustments for potential confounders are also strong points, noted Andrew Doig, PhD, professor of biochemistry, University of Manchester, Manchester, England.
“This is a significant result, comparable in effectiveness to the recent antibody drugs for Alzheimer’s disease,” Dr. Doig said. “Administering the recombinant shingles vaccine could well be a simple and cheap way to lower the risk of Alzheimer’s disease.”
Dr. Doig noted that a link between herpes zoster infection and the onset of dementia has been suspected for some time, and a trial of the antiviral drug valacyclovir against Alzheimer’s disease is currently underway.
In regard to the shingles vaccine, he said a placebo-controlled trial would be needed to prove causality.
“We also need to see how many years the effect might last and whether we should vaccinate people at a younger age. We know that the path to Alzheimer’s can start decades before any symptoms are apparent, so the vaccine might be even more effective if given to people in their 40s or 50s,” he said.
Dr. Harrison and Dr. Taquet reported no disclosures. Dr. Doig is a founder, director, and consultant for PharmaKure, which works on Alzheimer’s drugs and diagnostics. Other commentators declared no disclosures.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Commentary: IL-13 in PsA, PsA Risk, and Exercise, August 2024
Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Studies published last month have focused on identifying risk factors for psoriatic arthritis (PsA). An increasingly used method to study causality is Mendelian randomization (MR). MR uses genetic variation as a natural experiment to investigate the causal relationship between potentially modifiable risk factors and health outcomes in observational data.1Zhao and colleagues first identified a genetic variant in the IL13 gene to mimic the therapeutic effects of interleukin (IL)-13 inhibition in a genome-wide study of 563,946 individuals. To examine the effects of IL-13 inhibition and PsA, they then conducted a two-sample MR study using data from 3609 patients with PsA and 9192 control individuals without PsA. They demonstrated that IL-13 inhibition, genetically mimicked using the IL13 gene variant, was associated with an increased risk for PsA. This study provides evidence supporting the observation that treatment with IL-13 inhibitors (for atopic dermatitis and asthma) may increase the risk of developing PsA. Using similar MR methodology, Zhao and colleagues analyzed data from 3537 patients with PsA and 262,844 controls without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study.2 They demonstrated that apolipoprotein F increased the risk for PsA, whereas IL10 reduced the risk. Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and Septin-8.
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Commentary: Medication Overuse, Diet, and Parenting in Migraine, August 2024
Chronic migraine has a substantial impact on our patients' quality of life, potentially affecting mood, overall well-being, family life, relationships, and work. Many available medications can provide temporary relief of migraine symptoms, but treatment doesn't always prevent recurrence. Beyond the risk for side effects, excessive medication use can also induce medication withdrawal symptoms and rebound headaches. Medication overuse headache (MOH) is a known complication of migraine. The cycle of migraine and MOH can be hard to break, especially for adults who are parents of young children or adolescents. Managing migraine can be a challenge for parents, who may overuse migraine medication to attain temporary relief as they try to enjoy their families and attend to the continuous responsibilities of parenting. Furthermore, as all parents — including those with migraine — may neglect their own proper nutrition, it's important for treating physicians to remain attentive to the fact that diet has been shown to have an impact on migraine. Dietary considerations, including avoidance of migraine triggers and maintaining a nutrient-rich anti-inflammatory diet, are a safe way for patients to avoid migraine without adding to the risk for medication side effects or withdrawal. New research points to effective approaches that parents can use to manage their own migraines and to avoid or lessen MOH.
MOH involves many of the same features as migraine headaches: photophobia, nausea, vomiting, and sleep disturbances.1 Additionally, patients with migraine and comorbid MOH are at a higher risk for anxiety, depression, and emotional stress. MOH is difficult to treat, and symptom relapse after treatment is common. Results of a retrospective analysis published in July 2024 in The Journal of Headache and Facial Pain confirmed the effectiveness of calcitonin gene-related peptide (CGRP) antibody treatment in a real-world setting among migraine patients who had MOH. The study included a total of 291 patients who had been treated with either erenumab, fremanezumab, or galcanezumab. The majority of patients experienced a significant decline in monthly headache days, monthly migraine days, and monthly acute medication intake at 1 year. The researchers found that only 15.4% of the patients who initially met the criterion of chronic migraine with MOH relapsed, meeting the criterion for chronic migraine/MOH at the end of the 1-year follow-up period.
Lifestyle factors, such as diet, should be addressed when discussing migraine therapy with patients. Dietary factors, including a low–glycemic index diet, have been associated with promising results in migraine control. Results of a 10,359-patient cross-sectional study published in 2023 in the journal Nutrition confirmed that the inflammatory potential of patients' diet is associated with severe headache or migraine in US adults.2A more recent study, published in Frontiers in Nutrition in July 2024, examined dietary vitamin C intake of 13,445 individuals, of whom 20.42% had a severe headache or migraine. Vitamin C is a naturally occurring antioxidant and is also anti-inflammatory, found in foods such as citrus fruit, mangoes, strawberries, broccoli, and peppers. A subgroup analysis showed a significant association between vitamin C intake and severe headaches or migraines, with a reduced risk for severe headaches or migraines associated with an increased consumption of vitamin C. The authors noted that "each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine." Real-life application of this result for patients can involve encouraging patients to swap processed, low-nutrient foods in favor of fresh, nutrient-dense foods.
When treating migraine patients who are also parents, it is crucial to be persistent in searching for effective therapies to treat migraine and to treat or prevent MOH. According to a study published in 2018 in Headache, adolescents reported that parental migraine affected these factors in their lives: loss of parental support, reverse caregiving, emotional experience, interference with school, and missed activities and events.3 According to the authors of a more recent study, published in July 2024 in the Annals of General Psychiatry, parental migraine was significantly associated with an increased risk for attention-deficit/hyperactivity disorder, bipolar disorder, and depressive disorder among offspring of parents with migraine when compared with offspring of parents without migraine. The study authors noted that these outcomes could be the result of multiple factors, including psychosocial interactions, the burden of migraine on the family, and hereditary genetic traits. Nevertheless, even for offspring who may have a predisposition to these conditions because of genetic factors, effective treatment of parental migraine can relieve the day-to-day burden on the family, potentially reducing the effect of parental migraine on children. Parents who have migraine can become better equipped to provide attention to their children when their migraine symptoms are effectively treated. Furthermore, parents who have experienced improvement of their own migraine symptoms can offer hope and support if their children experience migraines, as migraine can be hereditary.
Additional References
1. Göçmez Yılmaz G, Ghouri R, et al. Complicated form of medication overuse headache is severe version of chronic migraine. J Clin Med. 2024;13(13):3696. doi: 10.3390/jcm13133696 Source
2. Liu H, Wang D, Wu F, et al. Association between inflammatory potential of diet and self-reported severe headache or migraine: A cross-sectional study of the National Health and Nutrition Examination Survey. Nutrition. 2023;113:112098. doi: 10.1016/j.nut.2023.112098 Source
3. Buse DC, Powers SW, Gelfand AA, et al. Adolescent perspectives on the burden of a parent's migraine: Results from the CaMEO Study. Headache. 2018;58(4):512-524. doi: 10.1111/head.13254 Source
Chronic migraine has a substantial impact on our patients' quality of life, potentially affecting mood, overall well-being, family life, relationships, and work. Many available medications can provide temporary relief of migraine symptoms, but treatment doesn't always prevent recurrence. Beyond the risk for side effects, excessive medication use can also induce medication withdrawal symptoms and rebound headaches. Medication overuse headache (MOH) is a known complication of migraine. The cycle of migraine and MOH can be hard to break, especially for adults who are parents of young children or adolescents. Managing migraine can be a challenge for parents, who may overuse migraine medication to attain temporary relief as they try to enjoy their families and attend to the continuous responsibilities of parenting. Furthermore, as all parents — including those with migraine — may neglect their own proper nutrition, it's important for treating physicians to remain attentive to the fact that diet has been shown to have an impact on migraine. Dietary considerations, including avoidance of migraine triggers and maintaining a nutrient-rich anti-inflammatory diet, are a safe way for patients to avoid migraine without adding to the risk for medication side effects or withdrawal. New research points to effective approaches that parents can use to manage their own migraines and to avoid or lessen MOH.
MOH involves many of the same features as migraine headaches: photophobia, nausea, vomiting, and sleep disturbances.1 Additionally, patients with migraine and comorbid MOH are at a higher risk for anxiety, depression, and emotional stress. MOH is difficult to treat, and symptom relapse after treatment is common. Results of a retrospective analysis published in July 2024 in The Journal of Headache and Facial Pain confirmed the effectiveness of calcitonin gene-related peptide (CGRP) antibody treatment in a real-world setting among migraine patients who had MOH. The study included a total of 291 patients who had been treated with either erenumab, fremanezumab, or galcanezumab. The majority of patients experienced a significant decline in monthly headache days, monthly migraine days, and monthly acute medication intake at 1 year. The researchers found that only 15.4% of the patients who initially met the criterion of chronic migraine with MOH relapsed, meeting the criterion for chronic migraine/MOH at the end of the 1-year follow-up period.
Lifestyle factors, such as diet, should be addressed when discussing migraine therapy with patients. Dietary factors, including a low–glycemic index diet, have been associated with promising results in migraine control. Results of a 10,359-patient cross-sectional study published in 2023 in the journal Nutrition confirmed that the inflammatory potential of patients' diet is associated with severe headache or migraine in US adults.2A more recent study, published in Frontiers in Nutrition in July 2024, examined dietary vitamin C intake of 13,445 individuals, of whom 20.42% had a severe headache or migraine. Vitamin C is a naturally occurring antioxidant and is also anti-inflammatory, found in foods such as citrus fruit, mangoes, strawberries, broccoli, and peppers. A subgroup analysis showed a significant association between vitamin C intake and severe headaches or migraines, with a reduced risk for severe headaches or migraines associated with an increased consumption of vitamin C. The authors noted that "each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine." Real-life application of this result for patients can involve encouraging patients to swap processed, low-nutrient foods in favor of fresh, nutrient-dense foods.
When treating migraine patients who are also parents, it is crucial to be persistent in searching for effective therapies to treat migraine and to treat or prevent MOH. According to a study published in 2018 in Headache, adolescents reported that parental migraine affected these factors in their lives: loss of parental support, reverse caregiving, emotional experience, interference with school, and missed activities and events.3 According to the authors of a more recent study, published in July 2024 in the Annals of General Psychiatry, parental migraine was significantly associated with an increased risk for attention-deficit/hyperactivity disorder, bipolar disorder, and depressive disorder among offspring of parents with migraine when compared with offspring of parents without migraine. The study authors noted that these outcomes could be the result of multiple factors, including psychosocial interactions, the burden of migraine on the family, and hereditary genetic traits. Nevertheless, even for offspring who may have a predisposition to these conditions because of genetic factors, effective treatment of parental migraine can relieve the day-to-day burden on the family, potentially reducing the effect of parental migraine on children. Parents who have migraine can become better equipped to provide attention to their children when their migraine symptoms are effectively treated. Furthermore, parents who have experienced improvement of their own migraine symptoms can offer hope and support if their children experience migraines, as migraine can be hereditary.
Additional References
1. Göçmez Yılmaz G, Ghouri R, et al. Complicated form of medication overuse headache is severe version of chronic migraine. J Clin Med. 2024;13(13):3696. doi: 10.3390/jcm13133696 Source
2. Liu H, Wang D, Wu F, et al. Association between inflammatory potential of diet and self-reported severe headache or migraine: A cross-sectional study of the National Health and Nutrition Examination Survey. Nutrition. 2023;113:112098. doi: 10.1016/j.nut.2023.112098 Source
3. Buse DC, Powers SW, Gelfand AA, et al. Adolescent perspectives on the burden of a parent's migraine: Results from the CaMEO Study. Headache. 2018;58(4):512-524. doi: 10.1111/head.13254 Source
Chronic migraine has a substantial impact on our patients' quality of life, potentially affecting mood, overall well-being, family life, relationships, and work. Many available medications can provide temporary relief of migraine symptoms, but treatment doesn't always prevent recurrence. Beyond the risk for side effects, excessive medication use can also induce medication withdrawal symptoms and rebound headaches. Medication overuse headache (MOH) is a known complication of migraine. The cycle of migraine and MOH can be hard to break, especially for adults who are parents of young children or adolescents. Managing migraine can be a challenge for parents, who may overuse migraine medication to attain temporary relief as they try to enjoy their families and attend to the continuous responsibilities of parenting. Furthermore, as all parents — including those with migraine — may neglect their own proper nutrition, it's important for treating physicians to remain attentive to the fact that diet has been shown to have an impact on migraine. Dietary considerations, including avoidance of migraine triggers and maintaining a nutrient-rich anti-inflammatory diet, are a safe way for patients to avoid migraine without adding to the risk for medication side effects or withdrawal. New research points to effective approaches that parents can use to manage their own migraines and to avoid or lessen MOH.
MOH involves many of the same features as migraine headaches: photophobia, nausea, vomiting, and sleep disturbances.1 Additionally, patients with migraine and comorbid MOH are at a higher risk for anxiety, depression, and emotional stress. MOH is difficult to treat, and symptom relapse after treatment is common. Results of a retrospective analysis published in July 2024 in The Journal of Headache and Facial Pain confirmed the effectiveness of calcitonin gene-related peptide (CGRP) antibody treatment in a real-world setting among migraine patients who had MOH. The study included a total of 291 patients who had been treated with either erenumab, fremanezumab, or galcanezumab. The majority of patients experienced a significant decline in monthly headache days, monthly migraine days, and monthly acute medication intake at 1 year. The researchers found that only 15.4% of the patients who initially met the criterion of chronic migraine with MOH relapsed, meeting the criterion for chronic migraine/MOH at the end of the 1-year follow-up period.
Lifestyle factors, such as diet, should be addressed when discussing migraine therapy with patients. Dietary factors, including a low–glycemic index diet, have been associated with promising results in migraine control. Results of a 10,359-patient cross-sectional study published in 2023 in the journal Nutrition confirmed that the inflammatory potential of patients' diet is associated with severe headache or migraine in US adults.2A more recent study, published in Frontiers in Nutrition in July 2024, examined dietary vitamin C intake of 13,445 individuals, of whom 20.42% had a severe headache or migraine. Vitamin C is a naturally occurring antioxidant and is also anti-inflammatory, found in foods such as citrus fruit, mangoes, strawberries, broccoli, and peppers. A subgroup analysis showed a significant association between vitamin C intake and severe headaches or migraines, with a reduced risk for severe headaches or migraines associated with an increased consumption of vitamin C. The authors noted that "each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine." Real-life application of this result for patients can involve encouraging patients to swap processed, low-nutrient foods in favor of fresh, nutrient-dense foods.
When treating migraine patients who are also parents, it is crucial to be persistent in searching for effective therapies to treat migraine and to treat or prevent MOH. According to a study published in 2018 in Headache, adolescents reported that parental migraine affected these factors in their lives: loss of parental support, reverse caregiving, emotional experience, interference with school, and missed activities and events.3 According to the authors of a more recent study, published in July 2024 in the Annals of General Psychiatry, parental migraine was significantly associated with an increased risk for attention-deficit/hyperactivity disorder, bipolar disorder, and depressive disorder among offspring of parents with migraine when compared with offspring of parents without migraine. The study authors noted that these outcomes could be the result of multiple factors, including psychosocial interactions, the burden of migraine on the family, and hereditary genetic traits. Nevertheless, even for offspring who may have a predisposition to these conditions because of genetic factors, effective treatment of parental migraine can relieve the day-to-day burden on the family, potentially reducing the effect of parental migraine on children. Parents who have migraine can become better equipped to provide attention to their children when their migraine symptoms are effectively treated. Furthermore, parents who have experienced improvement of their own migraine symptoms can offer hope and support if their children experience migraines, as migraine can be hereditary.
Additional References
1. Göçmez Yılmaz G, Ghouri R, et al. Complicated form of medication overuse headache is severe version of chronic migraine. J Clin Med. 2024;13(13):3696. doi: 10.3390/jcm13133696 Source
2. Liu H, Wang D, Wu F, et al. Association between inflammatory potential of diet and self-reported severe headache or migraine: A cross-sectional study of the National Health and Nutrition Examination Survey. Nutrition. 2023;113:112098. doi: 10.1016/j.nut.2023.112098 Source
3. Buse DC, Powers SW, Gelfand AA, et al. Adolescent perspectives on the burden of a parent's migraine: Results from the CaMEO Study. Headache. 2018;58(4):512-524. doi: 10.1111/head.13254 Source
Heat Waves: A Silent Threat to Older Adults’ Kidneys
TOPLINE:
Older adults show an increase in creatinine and cystatin C levels after exposure to extreme heat in a dry setting despite staying hydrated; however, changes in these kidney function biomarkers are much more modest in a humid setting and in young adults.
METHODOLOGY:
- Older adults are vulnerable to heat-related morbidity and mortality, with kidney complications accounting for many excess hospital admissions during heat waves.
- Researchers investigated plasma-based markers of kidney function following extreme heat exposure for 3 hours in 20 young (21-39 years) and 18 older (65-76 years) adults recruited from the Dallas-Fort Worth area.
- All participants underwent heat exposure in a chamber at 47 °C (116 °F) and 15% relative humidity (dry setting) and 41 °C (105 °F) and 40% relative humidity (humid setting) on separate days. They performed light physical activity mimicking their daily tasks and drank 3 mL/kg body mass of water every hour while exposed to heat.
- Blood samples were collected at baseline, immediately before the end of heat exposure (end-heating), and 2 hours after heat exposure.
- Plasma creatinine was the primary outcome, with a change ≥ 0.3 mg/dL considered as clinically meaningful. Cystatin C was the secondary outcome.
TAKEAWAY:
- The plasma creatinine level showed a modest increase from baseline to end-heating (difference, 0.10 mg/dL; P = .004) and at 2 hours post exposure (difference, 0.17 mg/dL; P < .001) in older adults facing heat exposure in the dry setting.
- The mean cystatin C levels also increased from baseline to end-heating by 0.29 mg/L (P = .01) and at 2 hours post heat exposure by 0.28 mg/L (P = .004) in older adults in the dry setting.
- The mean creatinine levels increased by only 0.06 mg/dL (P = .01) from baseline to 2 hours post exposure in older adults facing heat exposure in the humid setting.
- Young adults didn’t show any significant change in the plasma cystatin C levels during or after heat exposure; however, there was a modest increase in the plasma creatinine levels after 2 hours of heat exposure (difference, 0.06; P = .004).
IN PRACTICE:
“These findings provide limited evidence that the heightened thermal strain in older adults during extreme heat may contribute to reduced kidney function,” the authors wrote.
SOURCE:
The study was led by Zachary J. McKenna, PhD, from the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, and was published online in JAMA.
LIMITATIONS:
The use of plasma-based markers of kidney function, a short laboratory-based exposure, and a small number of generally healthy participants were the main limitations that could affect the generalizability of this study’s findings to broader populations and real-world settings.
DISCLOSURES:
The National Institutes of Health and American Heart Association funded this study. Two authors declared receiving grants and nonfinancial support from several sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Older adults show an increase in creatinine and cystatin C levels after exposure to extreme heat in a dry setting despite staying hydrated; however, changes in these kidney function biomarkers are much more modest in a humid setting and in young adults.
METHODOLOGY:
- Older adults are vulnerable to heat-related morbidity and mortality, with kidney complications accounting for many excess hospital admissions during heat waves.
- Researchers investigated plasma-based markers of kidney function following extreme heat exposure for 3 hours in 20 young (21-39 years) and 18 older (65-76 years) adults recruited from the Dallas-Fort Worth area.
- All participants underwent heat exposure in a chamber at 47 °C (116 °F) and 15% relative humidity (dry setting) and 41 °C (105 °F) and 40% relative humidity (humid setting) on separate days. They performed light physical activity mimicking their daily tasks and drank 3 mL/kg body mass of water every hour while exposed to heat.
- Blood samples were collected at baseline, immediately before the end of heat exposure (end-heating), and 2 hours after heat exposure.
- Plasma creatinine was the primary outcome, with a change ≥ 0.3 mg/dL considered as clinically meaningful. Cystatin C was the secondary outcome.
TAKEAWAY:
- The plasma creatinine level showed a modest increase from baseline to end-heating (difference, 0.10 mg/dL; P = .004) and at 2 hours post exposure (difference, 0.17 mg/dL; P < .001) in older adults facing heat exposure in the dry setting.
- The mean cystatin C levels also increased from baseline to end-heating by 0.29 mg/L (P = .01) and at 2 hours post heat exposure by 0.28 mg/L (P = .004) in older adults in the dry setting.
- The mean creatinine levels increased by only 0.06 mg/dL (P = .01) from baseline to 2 hours post exposure in older adults facing heat exposure in the humid setting.
- Young adults didn’t show any significant change in the plasma cystatin C levels during or after heat exposure; however, there was a modest increase in the plasma creatinine levels after 2 hours of heat exposure (difference, 0.06; P = .004).
IN PRACTICE:
“These findings provide limited evidence that the heightened thermal strain in older adults during extreme heat may contribute to reduced kidney function,” the authors wrote.
SOURCE:
The study was led by Zachary J. McKenna, PhD, from the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, and was published online in JAMA.
LIMITATIONS:
The use of plasma-based markers of kidney function, a short laboratory-based exposure, and a small number of generally healthy participants were the main limitations that could affect the generalizability of this study’s findings to broader populations and real-world settings.
DISCLOSURES:
The National Institutes of Health and American Heart Association funded this study. Two authors declared receiving grants and nonfinancial support from several sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Older adults show an increase in creatinine and cystatin C levels after exposure to extreme heat in a dry setting despite staying hydrated; however, changes in these kidney function biomarkers are much more modest in a humid setting and in young adults.
METHODOLOGY:
- Older adults are vulnerable to heat-related morbidity and mortality, with kidney complications accounting for many excess hospital admissions during heat waves.
- Researchers investigated plasma-based markers of kidney function following extreme heat exposure for 3 hours in 20 young (21-39 years) and 18 older (65-76 years) adults recruited from the Dallas-Fort Worth area.
- All participants underwent heat exposure in a chamber at 47 °C (116 °F) and 15% relative humidity (dry setting) and 41 °C (105 °F) and 40% relative humidity (humid setting) on separate days. They performed light physical activity mimicking their daily tasks and drank 3 mL/kg body mass of water every hour while exposed to heat.
- Blood samples were collected at baseline, immediately before the end of heat exposure (end-heating), and 2 hours after heat exposure.
- Plasma creatinine was the primary outcome, with a change ≥ 0.3 mg/dL considered as clinically meaningful. Cystatin C was the secondary outcome.
TAKEAWAY:
- The plasma creatinine level showed a modest increase from baseline to end-heating (difference, 0.10 mg/dL; P = .004) and at 2 hours post exposure (difference, 0.17 mg/dL; P < .001) in older adults facing heat exposure in the dry setting.
- The mean cystatin C levels also increased from baseline to end-heating by 0.29 mg/L (P = .01) and at 2 hours post heat exposure by 0.28 mg/L (P = .004) in older adults in the dry setting.
- The mean creatinine levels increased by only 0.06 mg/dL (P = .01) from baseline to 2 hours post exposure in older adults facing heat exposure in the humid setting.
- Young adults didn’t show any significant change in the plasma cystatin C levels during or after heat exposure; however, there was a modest increase in the plasma creatinine levels after 2 hours of heat exposure (difference, 0.06; P = .004).
IN PRACTICE:
“These findings provide limited evidence that the heightened thermal strain in older adults during extreme heat may contribute to reduced kidney function,” the authors wrote.
SOURCE:
The study was led by Zachary J. McKenna, PhD, from the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, and was published online in JAMA.
LIMITATIONS:
The use of plasma-based markers of kidney function, a short laboratory-based exposure, and a small number of generally healthy participants were the main limitations that could affect the generalizability of this study’s findings to broader populations and real-world settings.
DISCLOSURES:
The National Institutes of Health and American Heart Association funded this study. Two authors declared receiving grants and nonfinancial support from several sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Low Alcohol Use Offers No Clear Health Benefits
Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.
Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.
“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.
The findings were published in the Journal of Studies on Alcohol and Drugs.
The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.
For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.
When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.”
“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.
They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status.
A version of this article first appeared on WebMD.com.
Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.
Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.
“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.
The findings were published in the Journal of Studies on Alcohol and Drugs.
The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.
For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.
When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.”
“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.
They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status.
A version of this article first appeared on WebMD.com.
Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.
Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.
“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.
The findings were published in the Journal of Studies on Alcohol and Drugs.
The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.
For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.
When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.”
“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.
They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status.
A version of this article first appeared on WebMD.com.
FROM THE JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
Brain Structure Differs in Youth With Conduct Disorder
Youth with conduct disorder (CD) have extensive brain structure differences, new research showed.
“We know very little about this disorder even though it can carry a high burden for families and societies,” co–lead author Yidian Gao, PhD, of the University of Birmingham, Birmingham, England, said in a press release.
“The sample included in our study is 10-20 times larger than previous studies and contains data on children from North America, Europe, and Asia. It provides the most compelling evidence to date that CD is associated with widespread structural brain differences,” he added.
The findings were published online in The Lancet Psychiatry.
An Understudied Disorder
In the largest study of its kind, researchers at the Universities of Bath and Birmingham, both in England, collaborated with research teams across Europe, North America, and Asia, as part of the Enhancing NeuroImaging Genetics through Meta-Analysis–Antisocial Behavior Working Group to learn more about one of the “least researched psychiatric disorders,” they wrote.
The investigators used MRI to examine the brain structure of 1185 children with a clinical diagnosis of CD and 1253 typically developing children from 17-21 across 15 international study cohorts.
After adjusting for total intracranial volume investigators found that youth with CD (29% women; mean age, 13.7 years) had lower total surface area and lower regional surface area in 26 of the 34 cortical regions, spanning all four lobes of the brain, compared with their typically developing counterparts (35.6% women; mean age, 13.5 years).
Youth with CD also showed greater cortical thickness in the caudal anterior cingulate cortex (P = .0001) and lower cortical thickness in the banks of the superior temporal sulcus vs those without CD (P = .0010).
In addition, the CD group also had lower volume in the thalamus (P = .0009), amygdala (P = .0014), hippocampus (P = .0031), and nucleus accumbens (P = .0052).
Most findings remained significant after adjusting for intelligence quotient, psychiatric comorbidities, and psychotropic medication use. Of note, group difference in cortical thickness, 22 of 27 differences in surface area. In addition, three of four subcortical differences remained robust after adjusting for co-occurring attention-deficit/hyperactivity disorder, the most frequent comorbidity.
When the investigators divided individuals with CD into two subgroups — those with high vs low levels of callous-unemotional traits — they found limited overall differences. However, those with high callous-unemotional traits had lower surface area in the superior temporal and superior frontal gyri vs those with low callous-unemotional traits and the typically developing group.
Investigators also found that individuals with childhood-onset CD had greater cortical thickness in the caudal anterior cingulate cortex compared with those with adolescent-onset CD.
Study limitations include comparison of different cohorts with differing protocols that could affect the validity of the findings. In addition, subgroup samples were small and had lower statistical power.
“Our finding of robust brain alterations in conduct disorder — similar to those in more widely recognized and widely treated disorders such as ADHD — emphasize the need for a greater focus on conduct disorder in research, treatment, and public policy,” the authors noted.
Seven study authors reported conflicts of interest with various pharmaceutical companies and other organizations.
A version of this article first appeared on Medscape.com.
Youth with conduct disorder (CD) have extensive brain structure differences, new research showed.
“We know very little about this disorder even though it can carry a high burden for families and societies,” co–lead author Yidian Gao, PhD, of the University of Birmingham, Birmingham, England, said in a press release.
“The sample included in our study is 10-20 times larger than previous studies and contains data on children from North America, Europe, and Asia. It provides the most compelling evidence to date that CD is associated with widespread structural brain differences,” he added.
The findings were published online in The Lancet Psychiatry.
An Understudied Disorder
In the largest study of its kind, researchers at the Universities of Bath and Birmingham, both in England, collaborated with research teams across Europe, North America, and Asia, as part of the Enhancing NeuroImaging Genetics through Meta-Analysis–Antisocial Behavior Working Group to learn more about one of the “least researched psychiatric disorders,” they wrote.
The investigators used MRI to examine the brain structure of 1185 children with a clinical diagnosis of CD and 1253 typically developing children from 17-21 across 15 international study cohorts.
After adjusting for total intracranial volume investigators found that youth with CD (29% women; mean age, 13.7 years) had lower total surface area and lower regional surface area in 26 of the 34 cortical regions, spanning all four lobes of the brain, compared with their typically developing counterparts (35.6% women; mean age, 13.5 years).
Youth with CD also showed greater cortical thickness in the caudal anterior cingulate cortex (P = .0001) and lower cortical thickness in the banks of the superior temporal sulcus vs those without CD (P = .0010).
In addition, the CD group also had lower volume in the thalamus (P = .0009), amygdala (P = .0014), hippocampus (P = .0031), and nucleus accumbens (P = .0052).
Most findings remained significant after adjusting for intelligence quotient, psychiatric comorbidities, and psychotropic medication use. Of note, group difference in cortical thickness, 22 of 27 differences in surface area. In addition, three of four subcortical differences remained robust after adjusting for co-occurring attention-deficit/hyperactivity disorder, the most frequent comorbidity.
When the investigators divided individuals with CD into two subgroups — those with high vs low levels of callous-unemotional traits — they found limited overall differences. However, those with high callous-unemotional traits had lower surface area in the superior temporal and superior frontal gyri vs those with low callous-unemotional traits and the typically developing group.
Investigators also found that individuals with childhood-onset CD had greater cortical thickness in the caudal anterior cingulate cortex compared with those with adolescent-onset CD.
Study limitations include comparison of different cohorts with differing protocols that could affect the validity of the findings. In addition, subgroup samples were small and had lower statistical power.
“Our finding of robust brain alterations in conduct disorder — similar to those in more widely recognized and widely treated disorders such as ADHD — emphasize the need for a greater focus on conduct disorder in research, treatment, and public policy,” the authors noted.
Seven study authors reported conflicts of interest with various pharmaceutical companies and other organizations.
A version of this article first appeared on Medscape.com.
Youth with conduct disorder (CD) have extensive brain structure differences, new research showed.
“We know very little about this disorder even though it can carry a high burden for families and societies,” co–lead author Yidian Gao, PhD, of the University of Birmingham, Birmingham, England, said in a press release.
“The sample included in our study is 10-20 times larger than previous studies and contains data on children from North America, Europe, and Asia. It provides the most compelling evidence to date that CD is associated with widespread structural brain differences,” he added.
The findings were published online in The Lancet Psychiatry.
An Understudied Disorder
In the largest study of its kind, researchers at the Universities of Bath and Birmingham, both in England, collaborated with research teams across Europe, North America, and Asia, as part of the Enhancing NeuroImaging Genetics through Meta-Analysis–Antisocial Behavior Working Group to learn more about one of the “least researched psychiatric disorders,” they wrote.
The investigators used MRI to examine the brain structure of 1185 children with a clinical diagnosis of CD and 1253 typically developing children from 17-21 across 15 international study cohorts.
After adjusting for total intracranial volume investigators found that youth with CD (29% women; mean age, 13.7 years) had lower total surface area and lower regional surface area in 26 of the 34 cortical regions, spanning all four lobes of the brain, compared with their typically developing counterparts (35.6% women; mean age, 13.5 years).
Youth with CD also showed greater cortical thickness in the caudal anterior cingulate cortex (P = .0001) and lower cortical thickness in the banks of the superior temporal sulcus vs those without CD (P = .0010).
In addition, the CD group also had lower volume in the thalamus (P = .0009), amygdala (P = .0014), hippocampus (P = .0031), and nucleus accumbens (P = .0052).
Most findings remained significant after adjusting for intelligence quotient, psychiatric comorbidities, and psychotropic medication use. Of note, group difference in cortical thickness, 22 of 27 differences in surface area. In addition, three of four subcortical differences remained robust after adjusting for co-occurring attention-deficit/hyperactivity disorder, the most frequent comorbidity.
When the investigators divided individuals with CD into two subgroups — those with high vs low levels of callous-unemotional traits — they found limited overall differences. However, those with high callous-unemotional traits had lower surface area in the superior temporal and superior frontal gyri vs those with low callous-unemotional traits and the typically developing group.
Investigators also found that individuals with childhood-onset CD had greater cortical thickness in the caudal anterior cingulate cortex compared with those with adolescent-onset CD.
Study limitations include comparison of different cohorts with differing protocols that could affect the validity of the findings. In addition, subgroup samples were small and had lower statistical power.
“Our finding of robust brain alterations in conduct disorder — similar to those in more widely recognized and widely treated disorders such as ADHD — emphasize the need for a greater focus on conduct disorder in research, treatment, and public policy,” the authors noted.
Seven study authors reported conflicts of interest with various pharmaceutical companies and other organizations.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Physicians Call Out Barriers in Addiction Care
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
Bidirectional Link for Mental Health and Diabetic Complications
TOPLINE:
Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).
METHODOLOGY:
- Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
- The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
- Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.
TAKEAWAY:
- Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
- The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
- Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
- Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
- The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).
IN PRACTICE:
“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.
SOURCE:
The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.
LIMITATIONS:
The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.
DISCLOSURES:
The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).
METHODOLOGY:
- Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
- The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
- Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.
TAKEAWAY:
- Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
- The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
- Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
- Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
- The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).
IN PRACTICE:
“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.
SOURCE:
The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.
LIMITATIONS:
The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.
DISCLOSURES:
The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).
METHODOLOGY:
- Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
- The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
- Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.
TAKEAWAY:
- Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
- The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
- Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
- Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
- The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).
IN PRACTICE:
“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.
SOURCE:
The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.
LIMITATIONS:
The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.
DISCLOSURES:
The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.
A version of this article first appeared on Medscape.com.