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TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

• Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
• They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
• These studies spanned across four continents: Asia, Africa, Europe, and North America.
• The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

• The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
• Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

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 first appeared on Medscape.com.

TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

• Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
• They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
• These studies spanned across four continents: Asia, Africa, Europe, and North America.
• The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

• The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
• Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

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 first appeared on Medscape.com.

TOPLINE:

Hypermucoviscous Klebsiella pneumoniae (hmKp) strains demonstrate a significantly lower prevalence of extended-spectrum beta-lactamase (ESBL) production and slightly lower carbapenem resistance than non-hmKp strains, according to a recent meta-analysis of 2049 clinical isolates.

METHODOLOGY:

• Researchers conducted a meta-analysis to assess the prevalence of ESBL-producing strains and carbapenem-resistant strains among the hmKp and non-hmKp clinical isolates.
• They included 15 studies published between 2014 and 2023, with 2049 clinical isolates of K pneumoniae identified using a string test to distinguish hypermucoviscous from non-hypermucoviscous strains.
• These studies spanned across four continents: Asia, Africa, Europe, and North America.
• The primary outcome was the prevalence of ESBL-producing and carbapenem-resistant strains, determined through antimicrobial susceptibility testing.

TAKEAWAY:

• The hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains than non-hmKp strains (pooled odds ratio [OR], 0.26; P = .003).
• Similarly, hmKp strains were associated with a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR, 0.63; P = .038).

IN PRACTICE:

“Therapeutic options for CRKP [carbapenem-resistant K pneumoniae] infections are extremely limited due to the scarcity of effective antibacterial drugs. Therefore, it is crucial to consider the risks posed by CRKP strains when administering treatment to patients with hmKp infections and a history of the aforementioned risk factors,” the authors wrote.

SOURCE:

The study was led by Hiroki Namikawa, Department of Medical Education and General Practice, Graduate School of Medicine, Osaka Metropolitan University, Japan. It was published online on December 16, 2024, in Emerging Microbes & Infections.

LIMITATIONS:

Only three databases (PubMed, Scopus, and Cochrane Library) were searched for identifying studies, potentially missing relevant studies from other sources. Furthermore, only articles published in English were included, which may have restricted the scope of analysis. Additionally, geographical distribution was predominantly limited to Asia, limiting the global applicability of the results.

DISCLOSURES:

No funding sources were mentioned, and no conflicts of interest were reported.

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 first appeared on Medscape.com.

TOPLINE:

Patients with systemic lupus erythematosus (SLE) face more than double the risk for atherosclerotic plaque progression than healthy control individuals without the condition, but management of traditional cardiovascular risk factors and prolonged clinical remission can successfully mitigate it.

METHODOLOGY:

• Researchers performed a prospective study to assess the progression of subclinical atherosclerosis plaques and the development of cardiovascular events in patients with SLE over a 10-year follow-up period.
• They included 111 patients with SLE (mean age, 43 years; 91% women) and 94 matched healthy control individuals without prior atherosclerotic cardiovascular disease (CVD), active malignancy, pregnancy, or diabetes mellitus who underwent carotid ultrasound measurements.
• A total of 738 carotid measurements were analyzed from baseline to 3-, 7-, and 10-year follow-up periods for assessing new carotid plaque development; incident CVD events were also analyzed during follow-up.
• Disease remission was evaluated based on the Definition of Remission in SLE criteria.
• Target for management of cardiovascular risk factors was based on standard recommendations.
•  

TAKEAWAY:

• During the 10-year follow-up, patients with SLE showed a 2.3-fold higher risk for plaque progression than healthy control participants (adjusted incidence rate ratio [aIRR], 2.26; P = .002).
• Achieving risk reduction target for each standard cardiovascular risk factor (blood pressure, lipids, smoking, body weight, and physical activity) was associated with a 32% reduction in the risk for plaque progression (aIRR, 0.68; P = .004).
• Staying in remission for ≥ 75% of the follow-up period was significantly associated with a 43% reduction in the risk for plaque progression (aIRR, 0.57; P = .033).
• Patients with SLE also had a higher incidence of CVD events than healthy control participants (permutation-based log-rank P = .036).
•  

IN PRACTICE:

“These findings support the importance of prioritizing sustained remission rather than a low disease activity state for the prevention of atherosclerosis development and progression in SLE,” the authors wrote.

SOURCE:

The study was led by Nikolaos Papazoglou, MD, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens in Greece. It was published online on December 25, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had limited statistical power to perform a multivariate analysis of incident CVD events due to low event rates. The cohort consisted solely of White Europeans, possibly limiting the generalizability of the findings to more ethnically diverse populations. Because antiphospholipid antibodies are known to be associated with CVD events in the general population, the lack of testing for antiphospholipid antibody positivity in healthy control participants could be another limitation.

DISCLOSURES:

The study did not receive any funding from public, commercial, or not-for-profit sectors. The authors reported no competing interests.

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:

Patients with systemic lupus erythematosus (SLE) face more than double the risk for atherosclerotic plaque progression than healthy control individuals without the condition, but management of traditional cardiovascular risk factors and prolonged clinical remission can successfully mitigate it.

METHODOLOGY:

• Researchers performed a prospective study to assess the progression of subclinical atherosclerosis plaques and the development of cardiovascular events in patients with SLE over a 10-year follow-up period.
• They included 111 patients with SLE (mean age, 43 years; 91% women) and 94 matched healthy control individuals without prior atherosclerotic cardiovascular disease (CVD), active malignancy, pregnancy, or diabetes mellitus who underwent carotid ultrasound measurements.
• A total of 738 carotid measurements were analyzed from baseline to 3-, 7-, and 10-year follow-up periods for assessing new carotid plaque development; incident CVD events were also analyzed during follow-up.
• Disease remission was evaluated based on the Definition of Remission in SLE criteria.
• Target for management of cardiovascular risk factors was based on standard recommendations.
•  

TAKEAWAY:

• During the 10-year follow-up, patients with SLE showed a 2.3-fold higher risk for plaque progression than healthy control participants (adjusted incidence rate ratio [aIRR], 2.26; P = .002).
• Achieving risk reduction target for each standard cardiovascular risk factor (blood pressure, lipids, smoking, body weight, and physical activity) was associated with a 32% reduction in the risk for plaque progression (aIRR, 0.68; P = .004).
• Staying in remission for ≥ 75% of the follow-up period was significantly associated with a 43% reduction in the risk for plaque progression (aIRR, 0.57; P = .033).
• Patients with SLE also had a higher incidence of CVD events than healthy control participants (permutation-based log-rank P = .036).
•  

IN PRACTICE:

“These findings support the importance of prioritizing sustained remission rather than a low disease activity state for the prevention of atherosclerosis development and progression in SLE,” the authors wrote.

SOURCE:

The study was led by Nikolaos Papazoglou, MD, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens in Greece. It was published online on December 25, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had limited statistical power to perform a multivariate analysis of incident CVD events due to low event rates. The cohort consisted solely of White Europeans, possibly limiting the generalizability of the findings to more ethnically diverse populations. Because antiphospholipid antibodies are known to be associated with CVD events in the general population, the lack of testing for antiphospholipid antibody positivity in healthy control participants could be another limitation.

DISCLOSURES:

The study did not receive any funding from public, commercial, or not-for-profit sectors. The authors reported no competing interests.

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:

Patients with systemic lupus erythematosus (SLE) face more than double the risk for atherosclerotic plaque progression than healthy control individuals without the condition, but management of traditional cardiovascular risk factors and prolonged clinical remission can successfully mitigate it.

METHODOLOGY:

• Researchers performed a prospective study to assess the progression of subclinical atherosclerosis plaques and the development of cardiovascular events in patients with SLE over a 10-year follow-up period.
• They included 111 patients with SLE (mean age, 43 years; 91% women) and 94 matched healthy control individuals without prior atherosclerotic cardiovascular disease (CVD), active malignancy, pregnancy, or diabetes mellitus who underwent carotid ultrasound measurements.
• A total of 738 carotid measurements were analyzed from baseline to 3-, 7-, and 10-year follow-up periods for assessing new carotid plaque development; incident CVD events were also analyzed during follow-up.
• Disease remission was evaluated based on the Definition of Remission in SLE criteria.
• Target for management of cardiovascular risk factors was based on standard recommendations.
•  

TAKEAWAY:

• During the 10-year follow-up, patients with SLE showed a 2.3-fold higher risk for plaque progression than healthy control participants (adjusted incidence rate ratio [aIRR], 2.26; P = .002).
• Achieving risk reduction target for each standard cardiovascular risk factor (blood pressure, lipids, smoking, body weight, and physical activity) was associated with a 32% reduction in the risk for plaque progression (aIRR, 0.68; P = .004).
• Staying in remission for ≥ 75% of the follow-up period was significantly associated with a 43% reduction in the risk for plaque progression (aIRR, 0.57; P = .033).
• Patients with SLE also had a higher incidence of CVD events than healthy control participants (permutation-based log-rank P = .036).
•  

IN PRACTICE:

“These findings support the importance of prioritizing sustained remission rather than a low disease activity state for the prevention of atherosclerosis development and progression in SLE,” the authors wrote.

SOURCE:

The study was led by Nikolaos Papazoglou, MD, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens in Greece. It was published online on December 25, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had limited statistical power to perform a multivariate analysis of incident CVD events due to low event rates. The cohort consisted solely of White Europeans, possibly limiting the generalizability of the findings to more ethnically diverse populations. Because antiphospholipid antibodies are known to be associated with CVD events in the general population, the lack of testing for antiphospholipid antibody positivity in healthy control participants could be another limitation.

DISCLOSURES:

The study did not receive any funding from public, commercial, or not-for-profit sectors. The authors reported no competing interests.

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.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

The first human patient in the United States with a confirmed case of avian influenza has died, according to a press release from the Louisiana Department of Health. The individual was older than 65 years and had underlying medical conditions and remains the only known human case in the state.

The patient contracted highly pathogenic avian influenza, also known as H5N1, through exposure to wild birds and a noncommercial backyard flock, according to the release. The Louisiana Department of Health has found no additional H5H1 cases in the state and no evidence of person-to-person transmission.

The Centers for Disease Control and Prevention (CDC) conducted genetic sequencing of specimens of the virus collected from the Louisiana patient. The agency compared the sequences with sequences from dairy cows, wild birds, and poultry in various areas of the United States that were infected with the H5N1 virus.

The Louisiana patient was infected with the D1.1 genotype of the H5N1 virus. Although D1.1 is related to other D1.1 viruses found in recent human cases in Washington State and British Columbia, Canada, it is distinct from the widely spreading B3.13 genotype that has caused H5N1 outbreaks in dairy cows, poultry, and other animals and has been linked to sporadic human cases in the United States, according to the CDC.

Despite evidence of some changes in the virus between the Louisiana patient and samples from poultry on the patient’s property, “these changes would be more concerning if found in animal hosts or in early stages of infection,” according to the CDC. The CDC and the Louisiana Department of Health are conducting additional sequencing to facilitate further analysis.

In the meantime, the risk to the general public for H5N1 remains low, but individuals who work with or have recreational exposure to birds, poultry, or cows remain at increased risk.

The CDC and the Louisiana Department of Health advise individuals to reduce the risk for H5N1 exposure by avoiding direct contact with wild birds or other animals infected or possibly infected with the virus, avoiding any contact with dead animals, and keeping pets away from sick or dead animals and their feces. Additional safety measures include avoiding uncooked food products such as unpasteurized raw milk or cheese from animals with suspected or confirmed infections and reporting sick or dead birds or animals to the US Department of Agriculture by calling 1-866-536-7593 or the Louisiana Department of Agriculture and Forestry Diagnostic Lab by calling 318-927-3441.

The CDC advises clinicians to consider H5N1 in patients presenting with conjunctivitis or signs of acute respiratory illness and a history of high-risk exposure, including handling sick or dead animals, notably birds and livestock, within 10 days before the onset of symptoms. Other risk factors include consuming uncooked or undercooked food, direct contact with areas contaminated with feces, direct contact with unpasteurized milk or other dairy products or with parts of potentially infected animals, and prolonged exposure to infected animals in a confined space.

Clinical symptoms also may include gastrointestinal complaints such as diarrhea, as well as fatigue, arthralgia, and headache. Patients with more severe H5N1 may experience shortness of breath, altered mental state, and seizures, and serious complications of the virus include pneumonia, acute respiratory distress syndrome, multiorgan failure, and sepsis, according to the CDC.

Clinicians who suspect H5N1 cases should contact their local public health departments. The CDC offers additional advice on evaluating and managing patients with novel influenza A viruses.

 

A Clinician’s Take

“Some symptoms of avian flu include fever, cough, sore throat, runny nose, fatigue, body aches or eye redness or irritation,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at The University of Tennessee Health Science Center, Memphis, said in an interview. “The timing to the development of symptoms after exposure is typically within 10 days. Avian influenza should be considered when individuals develop symptoms with a relevant exposure history,” she said. 

Whenever possible, avoidance of sick or dead birds and other animals is ideal, but for those who must have contact with sick or dead birds, poultry, or other animals, personal protective equipment (PPE) including a respirator, goggles, and disposable gloves is recommended, said Mazumder. 

“For those working in high-exposure settings, additional PPE including boots or boot covers, hair cover, and fluid-resistant coveralls are recommended,” she said. “Other protective measures include avoiding touching surfaces or materials contaminated with feces, mucus, and saliva from infected animals and avoid[ing] the consumption of raw milk, raw milk products, and undercooked meat from infected animals,” she added.

Hunters handling wild game should dress birds in the field, practice good hand hygiene, and use a respirator or well-fitting mask and gloves when handling the animals to help prevent disease, said Mazumder. 

In addition, those working with confirmed or suspected H5N1 cases should monitor themselves for symptoms, said Mazumder. “Those who become ill within 10 days of exposure to an infected animal or source should isolate from household members and avoid going to work or school until infection is excluded. It is important to reach out to a healthcare professional if you think you may have been exposed or if you think you are infected,” she said. 

There is no currently available vaccine for H5N1 infection, but oseltamivir can be used for chemoprophylaxis and treatment, said Mazumder. “The seasonal flu vaccine does not protect against avian influenza; however, it is still important to ensure that you are up to date on the latest flu vaccine to prevent the possibility of a coinfection with seasonal flu and avian flu,” she emphasized. 

More research is needed to better understand how the influenza virus is transmitted, said Mazumder. “The potential for the virus to evolve and mutate, and how it affects different hosts, are all factors that can impact public health decisions,” she said. “In addition, further research into finding a vaccine and improving surveillance methods are necessary for disease prevention,” she said. 

Mazumder had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

The first human patient in the United States with a confirmed case of avian influenza has died, according to a press release from the Louisiana Department of Health. The individual was older than 65 years and had underlying medical conditions and remains the only known human case in the state.

The patient contracted highly pathogenic avian influenza, also known as H5N1, through exposure to wild birds and a noncommercial backyard flock, according to the release. The Louisiana Department of Health has found no additional H5H1 cases in the state and no evidence of person-to-person transmission.

The Centers for Disease Control and Prevention (CDC) conducted genetic sequencing of specimens of the virus collected from the Louisiana patient. The agency compared the sequences with sequences from dairy cows, wild birds, and poultry in various areas of the United States that were infected with the H5N1 virus.

The Louisiana patient was infected with the D1.1 genotype of the H5N1 virus. Although D1.1 is related to other D1.1 viruses found in recent human cases in Washington State and British Columbia, Canada, it is distinct from the widely spreading B3.13 genotype that has caused H5N1 outbreaks in dairy cows, poultry, and other animals and has been linked to sporadic human cases in the United States, according to the CDC.

Despite evidence of some changes in the virus between the Louisiana patient and samples from poultry on the patient’s property, “these changes would be more concerning if found in animal hosts or in early stages of infection,” according to the CDC. The CDC and the Louisiana Department of Health are conducting additional sequencing to facilitate further analysis.

In the meantime, the risk to the general public for H5N1 remains low, but individuals who work with or have recreational exposure to birds, poultry, or cows remain at increased risk.

The CDC and the Louisiana Department of Health advise individuals to reduce the risk for H5N1 exposure by avoiding direct contact with wild birds or other animals infected or possibly infected with the virus, avoiding any contact with dead animals, and keeping pets away from sick or dead animals and their feces. Additional safety measures include avoiding uncooked food products such as unpasteurized raw milk or cheese from animals with suspected or confirmed infections and reporting sick or dead birds or animals to the US Department of Agriculture by calling 1-866-536-7593 or the Louisiana Department of Agriculture and Forestry Diagnostic Lab by calling 318-927-3441.

The CDC advises clinicians to consider H5N1 in patients presenting with conjunctivitis or signs of acute respiratory illness and a history of high-risk exposure, including handling sick or dead animals, notably birds and livestock, within 10 days before the onset of symptoms. Other risk factors include consuming uncooked or undercooked food, direct contact with areas contaminated with feces, direct contact with unpasteurized milk or other dairy products or with parts of potentially infected animals, and prolonged exposure to infected animals in a confined space.

Clinical symptoms also may include gastrointestinal complaints such as diarrhea, as well as fatigue, arthralgia, and headache. Patients with more severe H5N1 may experience shortness of breath, altered mental state, and seizures, and serious complications of the virus include pneumonia, acute respiratory distress syndrome, multiorgan failure, and sepsis, according to the CDC.

Clinicians who suspect H5N1 cases should contact their local public health departments. The CDC offers additional advice on evaluating and managing patients with novel influenza A viruses.

 

A Clinician’s Take

“Some symptoms of avian flu include fever, cough, sore throat, runny nose, fatigue, body aches or eye redness or irritation,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at The University of Tennessee Health Science Center, Memphis, said in an interview. “The timing to the development of symptoms after exposure is typically within 10 days. Avian influenza should be considered when individuals develop symptoms with a relevant exposure history,” she said. 

Whenever possible, avoidance of sick or dead birds and other animals is ideal, but for those who must have contact with sick or dead birds, poultry, or other animals, personal protective equipment (PPE) including a respirator, goggles, and disposable gloves is recommended, said Mazumder. 

“For those working in high-exposure settings, additional PPE including boots or boot covers, hair cover, and fluid-resistant coveralls are recommended,” she said. “Other protective measures include avoiding touching surfaces or materials contaminated with feces, mucus, and saliva from infected animals and avoid[ing] the consumption of raw milk, raw milk products, and undercooked meat from infected animals,” she added.

Hunters handling wild game should dress birds in the field, practice good hand hygiene, and use a respirator or well-fitting mask and gloves when handling the animals to help prevent disease, said Mazumder. 

In addition, those working with confirmed or suspected H5N1 cases should monitor themselves for symptoms, said Mazumder. “Those who become ill within 10 days of exposure to an infected animal or source should isolate from household members and avoid going to work or school until infection is excluded. It is important to reach out to a healthcare professional if you think you may have been exposed or if you think you are infected,” she said. 

There is no currently available vaccine for H5N1 infection, but oseltamivir can be used for chemoprophylaxis and treatment, said Mazumder. “The seasonal flu vaccine does not protect against avian influenza; however, it is still important to ensure that you are up to date on the latest flu vaccine to prevent the possibility of a coinfection with seasonal flu and avian flu,” she emphasized. 

More research is needed to better understand how the influenza virus is transmitted, said Mazumder. “The potential for the virus to evolve and mutate, and how it affects different hosts, are all factors that can impact public health decisions,” she said. “In addition, further research into finding a vaccine and improving surveillance methods are necessary for disease prevention,” she said. 

Mazumder had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

The first human patient in the United States with a confirmed case of avian influenza has died, according to a press release from the Louisiana Department of Health. The individual was older than 65 years and had underlying medical conditions and remains the only known human case in the state.

The patient contracted highly pathogenic avian influenza, also known as H5N1, through exposure to wild birds and a noncommercial backyard flock, according to the release. The Louisiana Department of Health has found no additional H5H1 cases in the state and no evidence of person-to-person transmission.

The Centers for Disease Control and Prevention (CDC) conducted genetic sequencing of specimens of the virus collected from the Louisiana patient. The agency compared the sequences with sequences from dairy cows, wild birds, and poultry in various areas of the United States that were infected with the H5N1 virus.

The Louisiana patient was infected with the D1.1 genotype of the H5N1 virus. Although D1.1 is related to other D1.1 viruses found in recent human cases in Washington State and British Columbia, Canada, it is distinct from the widely spreading B3.13 genotype that has caused H5N1 outbreaks in dairy cows, poultry, and other animals and has been linked to sporadic human cases in the United States, according to the CDC.

Despite evidence of some changes in the virus between the Louisiana patient and samples from poultry on the patient’s property, “these changes would be more concerning if found in animal hosts or in early stages of infection,” according to the CDC. The CDC and the Louisiana Department of Health are conducting additional sequencing to facilitate further analysis.

In the meantime, the risk to the general public for H5N1 remains low, but individuals who work with or have recreational exposure to birds, poultry, or cows remain at increased risk.

The CDC and the Louisiana Department of Health advise individuals to reduce the risk for H5N1 exposure by avoiding direct contact with wild birds or other animals infected or possibly infected with the virus, avoiding any contact with dead animals, and keeping pets away from sick or dead animals and their feces. Additional safety measures include avoiding uncooked food products such as unpasteurized raw milk or cheese from animals with suspected or confirmed infections and reporting sick or dead birds or animals to the US Department of Agriculture by calling 1-866-536-7593 or the Louisiana Department of Agriculture and Forestry Diagnostic Lab by calling 318-927-3441.

The CDC advises clinicians to consider H5N1 in patients presenting with conjunctivitis or signs of acute respiratory illness and a history of high-risk exposure, including handling sick or dead animals, notably birds and livestock, within 10 days before the onset of symptoms. Other risk factors include consuming uncooked or undercooked food, direct contact with areas contaminated with feces, direct contact with unpasteurized milk or other dairy products or with parts of potentially infected animals, and prolonged exposure to infected animals in a confined space.

Clinical symptoms also may include gastrointestinal complaints such as diarrhea, as well as fatigue, arthralgia, and headache. Patients with more severe H5N1 may experience shortness of breath, altered mental state, and seizures, and serious complications of the virus include pneumonia, acute respiratory distress syndrome, multiorgan failure, and sepsis, according to the CDC.

Clinicians who suspect H5N1 cases should contact their local public health departments. The CDC offers additional advice on evaluating and managing patients with novel influenza A viruses.

 

A Clinician’s Take

“Some symptoms of avian flu include fever, cough, sore throat, runny nose, fatigue, body aches or eye redness or irritation,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at The University of Tennessee Health Science Center, Memphis, said in an interview. “The timing to the development of symptoms after exposure is typically within 10 days. Avian influenza should be considered when individuals develop symptoms with a relevant exposure history,” she said. 

Whenever possible, avoidance of sick or dead birds and other animals is ideal, but for those who must have contact with sick or dead birds, poultry, or other animals, personal protective equipment (PPE) including a respirator, goggles, and disposable gloves is recommended, said Mazumder. 

“For those working in high-exposure settings, additional PPE including boots or boot covers, hair cover, and fluid-resistant coveralls are recommended,” she said. “Other protective measures include avoiding touching surfaces or materials contaminated with feces, mucus, and saliva from infected animals and avoid[ing] the consumption of raw milk, raw milk products, and undercooked meat from infected animals,” she added.

Hunters handling wild game should dress birds in the field, practice good hand hygiene, and use a respirator or well-fitting mask and gloves when handling the animals to help prevent disease, said Mazumder. 

In addition, those working with confirmed or suspected H5N1 cases should monitor themselves for symptoms, said Mazumder. “Those who become ill within 10 days of exposure to an infected animal or source should isolate from household members and avoid going to work or school until infection is excluded. It is important to reach out to a healthcare professional if you think you may have been exposed or if you think you are infected,” she said. 

There is no currently available vaccine for H5N1 infection, but oseltamivir can be used for chemoprophylaxis and treatment, said Mazumder. “The seasonal flu vaccine does not protect against avian influenza; however, it is still important to ensure that you are up to date on the latest flu vaccine to prevent the possibility of a coinfection with seasonal flu and avian flu,” she emphasized. 

More research is needed to better understand how the influenza virus is transmitted, said Mazumder. “The potential for the virus to evolve and mutate, and how it affects different hosts, are all factors that can impact public health decisions,” she said. “In addition, further research into finding a vaccine and improving surveillance methods are necessary for disease prevention,” she said. 

Mazumder had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Donepezil was associated with improved verbal memory and enhanced recall and processing speed, compared with placebo, in patients with severe traumatic brain injury (TBI), with a favorable safety profile despite mild to moderate gastrointestinal side effects.

METHODOLOGY:

• A four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial (MEMRI-TBI-D) was conducted between 2013 and 2019 to evaluate the efficacy of donepezil for verbal memory impairments following severe TBI.
• 75 adults (75% men; mean age, 37 years) with complicated mild, moderate, or severe nonpenetrating TBI at least 6 months prior to study participation were included and randomly assigned to receive donepezil (n = 37) or placebo (n = 38).
• Participants received 5 mg donepezil daily or matching placebo for 2 weeks, then donepezil at 10 mg daily or matching placebo for 8 weeks; treatment was discontinued at 10 weeks, with an additional 4-week observation period.
• Verbal memory was assessed using the Hopkins Verbal Learning Test–Revised (HVLT-R). The primary outcome measure was verbal learning, evaluated through the HVLT-R total recall (ie, Total Trials 1-3) score.

TAKEAWAY:

• Compared with placebo, donepezil was associated with significantly greater improvements in verbal learning in both modified intent-to-treat and per-protocol analyses (P = .034 and .036, respectively).
• Treatment-responder rates were significantly higher in the donepezil group than in the placebo group (42 vs 18%; P = .03), with donepezil responders showing significant improvements in delayed recall and processing speed.
• Although there were no serious adverse events in either group, treatment-emergent adverse events were significantly more common in the donepezil group vs placebo (46% vs 8%; P < .001). No serious adverse events occurred in either group.
• Diarrhea and nausea were significantly more common in the donepezil group than in the placebo group (Fisher’s exact test: diarrhea, P = .03; nausea, P = .01).

IN PRACTICE:

“This study demonstrates the efficacy of donepezil on severe, persistent verbal memory impairments after predominantly severe TBI, with significant benefit for a subset of persons with such injuries, as well as a relatively favorable safety and tolerability profile,” the investigators wrote.

SOURCE:

The study was led by David B. Arciniegas, MD, University of Colorado School of Medicine, Aurora. It was published online in The Journal of Neuropsychiatry and Clinical Neurosciences.

LIMITATIONS:

The study included a relatively small sample with predominantly severe TBI requiring hospitalization and inpatient rehabilitation. The sample characteristics limit the generalizability of the findings to persons with other severities of TBI, other types of memory impairments, or more complex neuropsychiatric presentations. The study population had an average of 14 years of education, making generalizability to individuals with lower education levels uncertain. Additionally, while measures of information processing speed and immediate auditory attention were included, specific measures of sustained or selective attention were not, making it difficult to rule out improvements in higher-level attention as potential contributors to the observed verbal memory performance improvements.

DISCLOSURES:

The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research, with in-kind support from TIRR Memorial Hermann. Four authors disclosed various financial and professional affiliations, including advisory roles with pharmaceutical and diagnostic companies, support from institutional awards, and involvement in programs funded by external organizations. One author served as the editor of The Journal of Neuropsychiatry and Clinical Neurosciences, with an independent editor overseeing the review and publication process for this article.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

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 first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

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 first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

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 first appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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 first appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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 first appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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 first appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

Most of the papers I review merely validate a relationship that most of us, including the investigators, have already assumed based on common sense. However, every now and then I encounter a study whose findings clearly don’t support the researchers’ initial thesis. The most recent example of this unexpected finding is a paper designed to determine whether the sound of a crying infant would have an effect on a parent’s ability to accurately mix formula.

After a cursory reading of the investigators’ plan, most of us would have assumed from our own difficulties trying to accomplish something while our infant is crying that the crying would have a negative effect on our accuracy. Especially if it was a task that required careful measurement. However, when I skipped ahead to read the paper’s conclusion I was surprised that the investigators could found no significant negative relationship.

The explanation for this counterintuitive finding became readily apparent when I read the details of the study’s design more carefully. The investigators had chosen to use a generic recording of an infant crying, not the parent’s child nor even a live generic child on site.

No one enjoys listening to a child cry. It is certainly not a pleasant sound to the human ear. We seem to be hardwired to find it irritating. But, listening to our own child cry raises an entirely different suite of emotions, particularly if the child is close enough for us to intervene.

I’m not sure exactly what made the investigators choose a generic recording, but I suspect it was less expensive. Otherwise it would have required that the parents agree to subjecting their child to some stimulus that would have predictably induced the child to cry. Fortunately, the investigators were able to regroup in the wake of this lack of common sense in their experimental design and realized that, while their data failed to show a negative association with crying, it did provide an important message. Formula mixing errors, some with potentially harmful consequences, are far too common. In a commentary accompanying this paper, a pediatrician not involved in the study observes that, in our efforts to promote breastfeeding, we have given short shrift to teaching parents about accurate and safe formula preparation. 

But, let’s return to the crying piece. Why is it so difficult for parents to tolerate their own crying infant? Common sense should tell us that we know our infant is helpless. The little child is totally reliant on us to for nutrition and protection from the ever-present environmental threats to its health and safety in the environment. In short, whether we are parents, daycare providers, or the mother’s boyfriend who has been left in charge, we are totally responsible for the life of that infant, at times a heavy burden.

We must accept that from birth some of us are better able to tolerate and function with a crying infant in our care. That example of biologic variability is just one of the reasons why so many families find it difficult to set limits and follow through with consequences. When I have written about and spoken to parents in the office about discipline, I am happy if I can convince both parents to be on the same page (literally sometimes) in how they respond to their crying child.

Helping an infant learn to put itself to sleep is usually the first challenge that requires some agreement between parents on how long they can tolerate crying. Although allowing the infant to cry itself to sleep may be the best and most efficient strategy, it isn’t going to work when two parents and/or caregivers have widely different cry tolerances. In some situations these discrepancies can be managed by having the less tolerant parent temporarily move himself/herself to a location out of earshot. Something often easier said than accomplished.

At the heart of the solution is an acceptance by both parents that differing cry intolerances are not unusual and don’t imply that one partner is a better parent. As advisors we also must accept this reality and help the family find some other solution. Nothing is gained by allowing a disagreement between parents to make an already uncomfortable situation any worse.

While we don’t give out merit badges for it, being able to tolerate one’s own child crying for brief periods of time is a gift that can be helpful in certain situations. It is not a skill listed in the curriculum of most parenting classes, but learning more about what prompts babies to cry can be very helpful. This educational approach is exemplified by a Pediatrics Patient Page in a recent issue of JAMA Pediatrics. It’s rarely hunger and most often is sleep deprivation. It’s rarely the result of an undiscovered injury or medical condition, but may be a response to an overstimulating environment.

For those of us who are advisers, one of our responsibilities is to be alert to those few individuals whose intolerance to crying is so great that they are likely to injure the child or its mother to stop the crying. The simple question at an early well-child visit should be something like “How is everyone in the house when the child starts crying” might save a life. The stereotypic example is the young boyfriend of the mother, who may suspect that he is not the biologic father. However, any parent who is feeling insecure because of a financial situation, poor physical or mental health, or fatigue may lash out to achieve quiet. Crying is one of the realities of infancy. It is our job to help parents cope with it safely.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Most of the papers I review merely validate a relationship that most of us, including the investigators, have already assumed based on common sense. However, every now and then I encounter a study whose findings clearly don’t support the researchers’ initial thesis. The most recent example of this unexpected finding is a paper designed to determine whether the sound of a crying infant would have an effect on a parent’s ability to accurately mix formula.

After a cursory reading of the investigators’ plan, most of us would have assumed from our own difficulties trying to accomplish something while our infant is crying that the crying would have a negative effect on our accuracy. Especially if it was a task that required careful measurement. However, when I skipped ahead to read the paper’s conclusion I was surprised that the investigators could found no significant negative relationship.

The explanation for this counterintuitive finding became readily apparent when I read the details of the study’s design more carefully. The investigators had chosen to use a generic recording of an infant crying, not the parent’s child nor even a live generic child on site.

No one enjoys listening to a child cry. It is certainly not a pleasant sound to the human ear. We seem to be hardwired to find it irritating. But, listening to our own child cry raises an entirely different suite of emotions, particularly if the child is close enough for us to intervene.

I’m not sure exactly what made the investigators choose a generic recording, but I suspect it was less expensive. Otherwise it would have required that the parents agree to subjecting their child to some stimulus that would have predictably induced the child to cry. Fortunately, the investigators were able to regroup in the wake of this lack of common sense in their experimental design and realized that, while their data failed to show a negative association with crying, it did provide an important message. Formula mixing errors, some with potentially harmful consequences, are far too common. In a commentary accompanying this paper, a pediatrician not involved in the study observes that, in our efforts to promote breastfeeding, we have given short shrift to teaching parents about accurate and safe formula preparation. 

But, let’s return to the crying piece. Why is it so difficult for parents to tolerate their own crying infant? Common sense should tell us that we know our infant is helpless. The little child is totally reliant on us to for nutrition and protection from the ever-present environmental threats to its health and safety in the environment. In short, whether we are parents, daycare providers, or the mother’s boyfriend who has been left in charge, we are totally responsible for the life of that infant, at times a heavy burden.

We must accept that from birth some of us are better able to tolerate and function with a crying infant in our care. That example of biologic variability is just one of the reasons why so many families find it difficult to set limits and follow through with consequences. When I have written about and spoken to parents in the office about discipline, I am happy if I can convince both parents to be on the same page (literally sometimes) in how they respond to their crying child.

Helping an infant learn to put itself to sleep is usually the first challenge that requires some agreement between parents on how long they can tolerate crying. Although allowing the infant to cry itself to sleep may be the best and most efficient strategy, it isn’t going to work when two parents and/or caregivers have widely different cry tolerances. In some situations these discrepancies can be managed by having the less tolerant parent temporarily move himself/herself to a location out of earshot. Something often easier said than accomplished.

At the heart of the solution is an acceptance by both parents that differing cry intolerances are not unusual and don’t imply that one partner is a better parent. As advisors we also must accept this reality and help the family find some other solution. Nothing is gained by allowing a disagreement between parents to make an already uncomfortable situation any worse.

While we don’t give out merit badges for it, being able to tolerate one’s own child crying for brief periods of time is a gift that can be helpful in certain situations. It is not a skill listed in the curriculum of most parenting classes, but learning more about what prompts babies to cry can be very helpful. This educational approach is exemplified by a Pediatrics Patient Page in a recent issue of JAMA Pediatrics. It’s rarely hunger and most often is sleep deprivation. It’s rarely the result of an undiscovered injury or medical condition, but may be a response to an overstimulating environment.

For those of us who are advisers, one of our responsibilities is to be alert to those few individuals whose intolerance to crying is so great that they are likely to injure the child or its mother to stop the crying. The simple question at an early well-child visit should be something like “How is everyone in the house when the child starts crying” might save a life. The stereotypic example is the young boyfriend of the mother, who may suspect that he is not the biologic father. However, any parent who is feeling insecure because of a financial situation, poor physical or mental health, or fatigue may lash out to achieve quiet. Crying is one of the realities of infancy. It is our job to help parents cope with it safely.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Most of the papers I review merely validate a relationship that most of us, including the investigators, have already assumed based on common sense. However, every now and then I encounter a study whose findings clearly don’t support the researchers’ initial thesis. The most recent example of this unexpected finding is a paper designed to determine whether the sound of a crying infant would have an effect on a parent’s ability to accurately mix formula.

After a cursory reading of the investigators’ plan, most of us would have assumed from our own difficulties trying to accomplish something while our infant is crying that the crying would have a negative effect on our accuracy. Especially if it was a task that required careful measurement. However, when I skipped ahead to read the paper’s conclusion I was surprised that the investigators could found no significant negative relationship.

The explanation for this counterintuitive finding became readily apparent when I read the details of the study’s design more carefully. The investigators had chosen to use a generic recording of an infant crying, not the parent’s child nor even a live generic child on site.

No one enjoys listening to a child cry. It is certainly not a pleasant sound to the human ear. We seem to be hardwired to find it irritating. But, listening to our own child cry raises an entirely different suite of emotions, particularly if the child is close enough for us to intervene.

I’m not sure exactly what made the investigators choose a generic recording, but I suspect it was less expensive. Otherwise it would have required that the parents agree to subjecting their child to some stimulus that would have predictably induced the child to cry. Fortunately, the investigators were able to regroup in the wake of this lack of common sense in their experimental design and realized that, while their data failed to show a negative association with crying, it did provide an important message. Formula mixing errors, some with potentially harmful consequences, are far too common. In a commentary accompanying this paper, a pediatrician not involved in the study observes that, in our efforts to promote breastfeeding, we have given short shrift to teaching parents about accurate and safe formula preparation. 

But, let’s return to the crying piece. Why is it so difficult for parents to tolerate their own crying infant? Common sense should tell us that we know our infant is helpless. The little child is totally reliant on us to for nutrition and protection from the ever-present environmental threats to its health and safety in the environment. In short, whether we are parents, daycare providers, or the mother’s boyfriend who has been left in charge, we are totally responsible for the life of that infant, at times a heavy burden.

We must accept that from birth some of us are better able to tolerate and function with a crying infant in our care. That example of biologic variability is just one of the reasons why so many families find it difficult to set limits and follow through with consequences. When I have written about and spoken to parents in the office about discipline, I am happy if I can convince both parents to be on the same page (literally sometimes) in how they respond to their crying child.

Helping an infant learn to put itself to sleep is usually the first challenge that requires some agreement between parents on how long they can tolerate crying. Although allowing the infant to cry itself to sleep may be the best and most efficient strategy, it isn’t going to work when two parents and/or caregivers have widely different cry tolerances. In some situations these discrepancies can be managed by having the less tolerant parent temporarily move himself/herself to a location out of earshot. Something often easier said than accomplished.

At the heart of the solution is an acceptance by both parents that differing cry intolerances are not unusual and don’t imply that one partner is a better parent. As advisors we also must accept this reality and help the family find some other solution. Nothing is gained by allowing a disagreement between parents to make an already uncomfortable situation any worse.

While we don’t give out merit badges for it, being able to tolerate one’s own child crying for brief periods of time is a gift that can be helpful in certain situations. It is not a skill listed in the curriculum of most parenting classes, but learning more about what prompts babies to cry can be very helpful. This educational approach is exemplified by a Pediatrics Patient Page in a recent issue of JAMA Pediatrics. It’s rarely hunger and most often is sleep deprivation. It’s rarely the result of an undiscovered injury or medical condition, but may be a response to an overstimulating environment.

For those of us who are advisers, one of our responsibilities is to be alert to those few individuals whose intolerance to crying is so great that they are likely to injure the child or its mother to stop the crying. The simple question at an early well-child visit should be something like “How is everyone in the house when the child starts crying” might save a life. The stereotypic example is the young boyfriend of the mother, who may suspect that he is not the biologic father. However, any parent who is feeling insecure because of a financial situation, poor physical or mental health, or fatigue may lash out to achieve quiet. Crying is one of the realities of infancy. It is our job to help parents cope with it safely.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

At the close of 2024, to an odd mix of disappointment and jubilation, Cassava Sciences announced that simufilam didn’t do anything for Alzheimer’s disease.

An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.

Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.

 

But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.

Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.

As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”

Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.

Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.

At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.

I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.

But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.

They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

At the close of 2024, to an odd mix of disappointment and jubilation, Cassava Sciences announced that simufilam didn’t do anything for Alzheimer’s disease.

An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.

Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.

 

But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.

Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.

As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”

Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.

Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.

At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.

I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.

But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.

They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

At the close of 2024, to an odd mix of disappointment and jubilation, Cassava Sciences announced that simufilam didn’t do anything for Alzheimer’s disease.

An Alzheimer’s drug trial failing is, unfortunately, nothing new. This one, however, had more baggage behind it than most.

Like all of these things, it was worth a try. It’s an interesting molecule with a reasonable mechanism of action.

 

But the trials have been raising questions for a few years, with allegations of misconduct against the drug’s co-discoverer Hoau-Yan Wang. He’s been indicted for defrauding the National Institutes of Health of $16 million in grants related to the drug. There have been concerns over doctored images and other not-so-minor issues in trying to move simufilam forward. Cassava itself agreed to pay the Securities and Exchange Commission $40 million in 2024 to settle charges about misleading investors.

Yet, like an innocent child with criminal parents, many of us hoped that the drug would work, regardless of the ethical shenanigans behind it. On the front lines we deal with a tragic disease that robs people of what makes them human and robs the families who have to live with it.

As the wheels started to come off the bus I told a friend, “it would be really sad if this drug is THE ONE and it never gets to finish trials because of everything else.”

Now we know it isn’t. Regardless of the controversy, the final data show that simufilam is just another placebo, joining the ranks of many others in the Alzheimer’s development graveyard.

Yes, there is a vague sense of jubilation behind it. I believe in fair play, and it’s good to know that those who misled investors and falsified data were wrong and will never have their day in the sun.

At the same time, however, I’m disappointed. I’m happy that the drug at least got a chance to prove itself, but when it’s all said and done, it doesn’t do anything.

I feel bad for the innocent people in the company, who had nothing to do with the scheming and were just hoping the drug would go somewhere. The majority, if not all, of them will likely lose their jobs. Like me, they have families, bills, and mortgages.

But I’m even more disappointed for the patients and families who only wanted an effective treatment for Alzheimer’s disease, and were hoping that, regardless of its dirty laundry, simufilam would work.

They’re the ones that I, and many other neurologists, have to face every day when they ask “is there anything new out?” and we sadly shake our heads.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.