To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.

Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.

“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”

According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.

To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.

The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.

Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)

“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.

Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).

“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”

Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.

In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.

“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”

They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.

“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”

Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”

Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.

“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”

The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.

Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.

“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”

The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.

“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”

The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.

They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.

Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.

In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).

However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.

“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.

Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.

“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”

However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.

“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.

He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”

There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.

Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.

“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”

The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.

“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”

The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.

They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.

Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.

In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).

However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.

“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.

Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.

“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”

However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.

“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.

He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”

There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.

Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.

“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”

The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.

“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”

The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.

They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.

Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.

In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.

Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).

However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.

“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.

Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.

“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”

However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.

“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.

He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

[email protected]

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

[email protected]

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

[email protected]

Shared decision-making is an integral step in lung cancer screening with low-dose CT (LDCT) in high-risk patients, but a cross-sectional study at two academic medical centers in Texas has found wide variability in the quality of shared decision-making encounters and that nearly a third of patients reported being conflicted about their decisions to pursue screening.

Lead author Shawn P.E. Nishi, MD, associate professor in the division of pulmonary critical care and sleep medicine, department of internal medicine, of the University of Texas Medical Branch, Galveston, noted two striking findings of the study, published in Chest: that physicians rarely used decision aids according to Centers for Medicare & Medicaid Services direction, and that a “considerable imbalance” exists in the way physicians present management choices to patients. “As physicians, we want to focus on the positive,” she said, “but in shared decision-making (SDM) there needs to be a better balance between presentation and understanding of the risks and the benefits of lung cancer screening (LCS).”

Since 2015, CMS has reimbursed for LCS counseling and an shared decision-making visit before a patient has the screening.

The study analyzed self-reported survey results of 266 patients who had been through SDM at UTMB Galveston and MD Anderson Cancer Center in Houston in 2017. They completed patient surveys the following year. The study population was 87% White, 38% had a family history of lung cancer, and 39% were current smokers. The mean pack-year history was 40.4 years.

A high percentage – 86.6% – said they were satisfied with the level in which they were involved in their screening decision. Patients reported that their doctors talked to them about the benefits of LCS far more frequently than the potential harms, 68.3% to 20.8%. And 12.5% said they understood that an abnormal scan was likely to result in a negative finding. Only 30.7% said they’d received educational materials about LCS during the screening process.

A year after completing the SDM process, their knowledge of LCS was variable at best; on average, they answered 41.4% of the questions correctly, and almost one-third (31%) indicated that screening, rather than quitting smoking, was the best way reduce their lung cancer risk.

The study noted that, for patients who derive a small benefit from LCS, the absolute risk reduction is only 0.3%, which may not be enough to offset the potential harms of LDCT.

“The LCS exam itself is a simple noninvasive procedure; you get a scan and go about your day once it’s read,” Dr. Nishi said. “However there is a high false-positive rate, and the question really becomes that, as you start to work up those false positives and even true positives, however small, there is a risk associated with every procedure or evaluation thereafter. So the shared decision-making process is really there to ensure that patients value finding their lung cancer early if they do have it versus the potential harms down the line.”

However, as this study points out, there aren’t many parameters for what SDM entails. “It’s more than just an information exchange back and forth,” Dr. Nishi said. “It’s about having good-quality communication between the provider and patients so that the right decision can ultimately be made for each patient. It takes a very dedicated person that can commit the time and expertise to it. I don’t think that it should be taken lightly.”

As Dr. Nishi and colleagues pointed out in their study, SDM incorporates three essential elements: recognizing and acknowledging that a decision has to be made, knowing and understanding the best available evidence, and incorporating the patient’s own values and preferences in the decision.

CMS outlines specific components of SDM. It includes, beyond a discussion of the potential benefits and harms and use of a decision aid, education on the need for adherence to annual screening, and counseling on either stopping smoking or continued abstinence.

For physicians, dedicating the time and energy SDM needs can be a challenge, Dr. Nishi noted, “Health care doesn’t have a lot of support to perform shared decision-making,” she said. “In a very busy practice it’s very hard to make sure you have a good process where you can sit down and take all the time you need with a patient to open up a dialog about the risks and benefits.”

After they completed the screening process, 33.6% of patients said they had some conflicting feelings about their decision. Non-White patients were about four times more likely than White patients to feel conflicted about their choices (odds ratio, 4.31; 95% confidence interval, 1.36-13.70), as were former smokers, compared with current smokers (OR, 1.93; 95% CI, 1.04-3.55).

Future studies of SDM in LCS should focus on outcomes, said Dr. Nishi. “Hopefully then we can focus on those things that benefit patients the most.”

Abbie Begnaud, MD, FCCP, a pulmonologist at the University of Minnesota, Minneapolis, said this study confirmed what other studies found about shortcomings of SDM, with one difference. “We already knew we were not doing a great job at shared decision-making,” she said. “To me, the difference in this study is that most of the patients were pretty satisfied with their degree of involvement.”

She noted the low percentage of patients who understood that abnormal scans may be noncancerous. “This is one area that I think is an important place for us to improve,” Dr. Begnaud said.

The findings about non-White patients and former smokers are also telling, Dr. Begnaud said. “This highlights that we need to pay close attention to these two groups – people who have traditionally, historically been marginalized in medical care – and provide them the support they need to make a decision.”

Dr. Nishi and colleagues have no relevant disclosures. The study was supported by the Cancer Prevention and Research Institute of Texas and received grants from the National Cancer Institute and the University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment. Dr. Begnaud has no relevant relationships to disclose.

Shared decision-making is an integral step in lung cancer screening with low-dose CT (LDCT) in high-risk patients, but a cross-sectional study at two academic medical centers in Texas has found wide variability in the quality of shared decision-making encounters and that nearly a third of patients reported being conflicted about their decisions to pursue screening.

Lead author Shawn P.E. Nishi, MD, associate professor in the division of pulmonary critical care and sleep medicine, department of internal medicine, of the University of Texas Medical Branch, Galveston, noted two striking findings of the study, published in Chest: that physicians rarely used decision aids according to Centers for Medicare & Medicaid Services direction, and that a “considerable imbalance” exists in the way physicians present management choices to patients. “As physicians, we want to focus on the positive,” she said, “but in shared decision-making (SDM) there needs to be a better balance between presentation and understanding of the risks and the benefits of lung cancer screening (LCS).”

Since 2015, CMS has reimbursed for LCS counseling and an shared decision-making visit before a patient has the screening.

The study analyzed self-reported survey results of 266 patients who had been through SDM at UTMB Galveston and MD Anderson Cancer Center in Houston in 2017. They completed patient surveys the following year. The study population was 87% White, 38% had a family history of lung cancer, and 39% were current smokers. The mean pack-year history was 40.4 years.

A high percentage – 86.6% – said they were satisfied with the level in which they were involved in their screening decision. Patients reported that their doctors talked to them about the benefits of LCS far more frequently than the potential harms, 68.3% to 20.8%. And 12.5% said they understood that an abnormal scan was likely to result in a negative finding. Only 30.7% said they’d received educational materials about LCS during the screening process.

A year after completing the SDM process, their knowledge of LCS was variable at best; on average, they answered 41.4% of the questions correctly, and almost one-third (31%) indicated that screening, rather than quitting smoking, was the best way reduce their lung cancer risk.

The study noted that, for patients who derive a small benefit from LCS, the absolute risk reduction is only 0.3%, which may not be enough to offset the potential harms of LDCT.

“The LCS exam itself is a simple noninvasive procedure; you get a scan and go about your day once it’s read,” Dr. Nishi said. “However there is a high false-positive rate, and the question really becomes that, as you start to work up those false positives and even true positives, however small, there is a risk associated with every procedure or evaluation thereafter. So the shared decision-making process is really there to ensure that patients value finding their lung cancer early if they do have it versus the potential harms down the line.”

However, as this study points out, there aren’t many parameters for what SDM entails. “It’s more than just an information exchange back and forth,” Dr. Nishi said. “It’s about having good-quality communication between the provider and patients so that the right decision can ultimately be made for each patient. It takes a very dedicated person that can commit the time and expertise to it. I don’t think that it should be taken lightly.”

As Dr. Nishi and colleagues pointed out in their study, SDM incorporates three essential elements: recognizing and acknowledging that a decision has to be made, knowing and understanding the best available evidence, and incorporating the patient’s own values and preferences in the decision.

CMS outlines specific components of SDM. It includes, beyond a discussion of the potential benefits and harms and use of a decision aid, education on the need for adherence to annual screening, and counseling on either stopping smoking or continued abstinence.

For physicians, dedicating the time and energy SDM needs can be a challenge, Dr. Nishi noted, “Health care doesn’t have a lot of support to perform shared decision-making,” she said. “In a very busy practice it’s very hard to make sure you have a good process where you can sit down and take all the time you need with a patient to open up a dialog about the risks and benefits.”

After they completed the screening process, 33.6% of patients said they had some conflicting feelings about their decision. Non-White patients were about four times more likely than White patients to feel conflicted about their choices (odds ratio, 4.31; 95% confidence interval, 1.36-13.70), as were former smokers, compared with current smokers (OR, 1.93; 95% CI, 1.04-3.55).

Future studies of SDM in LCS should focus on outcomes, said Dr. Nishi. “Hopefully then we can focus on those things that benefit patients the most.”

Abbie Begnaud, MD, FCCP, a pulmonologist at the University of Minnesota, Minneapolis, said this study confirmed what other studies found about shortcomings of SDM, with one difference. “We already knew we were not doing a great job at shared decision-making,” she said. “To me, the difference in this study is that most of the patients were pretty satisfied with their degree of involvement.”

She noted the low percentage of patients who understood that abnormal scans may be noncancerous. “This is one area that I think is an important place for us to improve,” Dr. Begnaud said.

The findings about non-White patients and former smokers are also telling, Dr. Begnaud said. “This highlights that we need to pay close attention to these two groups – people who have traditionally, historically been marginalized in medical care – and provide them the support they need to make a decision.”

Dr. Nishi and colleagues have no relevant disclosures. The study was supported by the Cancer Prevention and Research Institute of Texas and received grants from the National Cancer Institute and the University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment. Dr. Begnaud has no relevant relationships to disclose.

Shared decision-making is an integral step in lung cancer screening with low-dose CT (LDCT) in high-risk patients, but a cross-sectional study at two academic medical centers in Texas has found wide variability in the quality of shared decision-making encounters and that nearly a third of patients reported being conflicted about their decisions to pursue screening.

Lead author Shawn P.E. Nishi, MD, associate professor in the division of pulmonary critical care and sleep medicine, department of internal medicine, of the University of Texas Medical Branch, Galveston, noted two striking findings of the study, published in Chest: that physicians rarely used decision aids according to Centers for Medicare & Medicaid Services direction, and that a “considerable imbalance” exists in the way physicians present management choices to patients. “As physicians, we want to focus on the positive,” she said, “but in shared decision-making (SDM) there needs to be a better balance between presentation and understanding of the risks and the benefits of lung cancer screening (LCS).”

Since 2015, CMS has reimbursed for LCS counseling and an shared decision-making visit before a patient has the screening.

The study analyzed self-reported survey results of 266 patients who had been through SDM at UTMB Galveston and MD Anderson Cancer Center in Houston in 2017. They completed patient surveys the following year. The study population was 87% White, 38% had a family history of lung cancer, and 39% were current smokers. The mean pack-year history was 40.4 years.

A high percentage – 86.6% – said they were satisfied with the level in which they were involved in their screening decision. Patients reported that their doctors talked to them about the benefits of LCS far more frequently than the potential harms, 68.3% to 20.8%. And 12.5% said they understood that an abnormal scan was likely to result in a negative finding. Only 30.7% said they’d received educational materials about LCS during the screening process.

A year after completing the SDM process, their knowledge of LCS was variable at best; on average, they answered 41.4% of the questions correctly, and almost one-third (31%) indicated that screening, rather than quitting smoking, was the best way reduce their lung cancer risk.

The study noted that, for patients who derive a small benefit from LCS, the absolute risk reduction is only 0.3%, which may not be enough to offset the potential harms of LDCT.

“The LCS exam itself is a simple noninvasive procedure; you get a scan and go about your day once it’s read,” Dr. Nishi said. “However there is a high false-positive rate, and the question really becomes that, as you start to work up those false positives and even true positives, however small, there is a risk associated with every procedure or evaluation thereafter. So the shared decision-making process is really there to ensure that patients value finding their lung cancer early if they do have it versus the potential harms down the line.”

However, as this study points out, there aren’t many parameters for what SDM entails. “It’s more than just an information exchange back and forth,” Dr. Nishi said. “It’s about having good-quality communication between the provider and patients so that the right decision can ultimately be made for each patient. It takes a very dedicated person that can commit the time and expertise to it. I don’t think that it should be taken lightly.”

As Dr. Nishi and colleagues pointed out in their study, SDM incorporates three essential elements: recognizing and acknowledging that a decision has to be made, knowing and understanding the best available evidence, and incorporating the patient’s own values and preferences in the decision.

CMS outlines specific components of SDM. It includes, beyond a discussion of the potential benefits and harms and use of a decision aid, education on the need for adherence to annual screening, and counseling on either stopping smoking or continued abstinence.

For physicians, dedicating the time and energy SDM needs can be a challenge, Dr. Nishi noted, “Health care doesn’t have a lot of support to perform shared decision-making,” she said. “In a very busy practice it’s very hard to make sure you have a good process where you can sit down and take all the time you need with a patient to open up a dialog about the risks and benefits.”

After they completed the screening process, 33.6% of patients said they had some conflicting feelings about their decision. Non-White patients were about four times more likely than White patients to feel conflicted about their choices (odds ratio, 4.31; 95% confidence interval, 1.36-13.70), as were former smokers, compared with current smokers (OR, 1.93; 95% CI, 1.04-3.55).

Future studies of SDM in LCS should focus on outcomes, said Dr. Nishi. “Hopefully then we can focus on those things that benefit patients the most.”

Abbie Begnaud, MD, FCCP, a pulmonologist at the University of Minnesota, Minneapolis, said this study confirmed what other studies found about shortcomings of SDM, with one difference. “We already knew we were not doing a great job at shared decision-making,” she said. “To me, the difference in this study is that most of the patients were pretty satisfied with their degree of involvement.”

She noted the low percentage of patients who understood that abnormal scans may be noncancerous. “This is one area that I think is an important place for us to improve,” Dr. Begnaud said.

The findings about non-White patients and former smokers are also telling, Dr. Begnaud said. “This highlights that we need to pay close attention to these two groups – people who have traditionally, historically been marginalized in medical care – and provide them the support they need to make a decision.”

Dr. Nishi and colleagues have no relevant disclosures. The study was supported by the Cancer Prevention and Research Institute of Texas and received grants from the National Cancer Institute and the University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment. Dr. Begnaud has no relevant relationships to disclose.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]