Federal Practitioner

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

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

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

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

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy – but note that several other oral and topical therapies may help ease pain.

Painful diabetic neuropathy is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan, Ann Arbor, noted in a news release.

“This guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Dr. Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of painful diabetic neuropathy. The new guidance was published online Dec. 27, 2021, in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.
 

Multiple options

To update the guideline, an expert panel reviewed data from more than 100 randomized controlled trials published from January 2008 to April 2020.

The panel noted that more than 16% of individuals with diabetes experience painful diabetic neuropathy, but it often goes unrecognized and untreated. The guideline recommends clinicians assess patients with diabetes for peripheral neuropathic pain and its effect on their function and quality of life.

Before prescribing treatment, health providers should determine if the patient also has mood or sleep problems as both can influence pain perception.

The guideline recommends offering one of four classes of oral medications found to be effective for neuropathic pain: tricyclic antidepressants such as amitriptyline, nortriptyline, or imipramine; serotonin norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, or desvenlafaxine; gabapentinoids such as gabapentin or pregabalin; and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide.

All four classes of medications have “comparable effect sizes just above or just below our cutoff for a medium effect size” (standardized median difference, 0.5), the panel noted.

In addition, “new studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said Dr. Callaghan.

When an initial medication fails to provide meaningful improvement in pain, or produces significant side effects, a trial of another medication from a different class is recommended.
 

Pain reduction, not elimination

Opioids are not recommended for painful diabetic neuropathy. Not only do they come with risks, there is also no strong evidence they are effective for painful diabetic neuropathy in the long term, the panel wrote. Tramadol and tapentadol are also not recommended for the treatment of painful diabetic neuropathy.

“Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” Dr. Callaghan said.

For patients interested in trying topical, nontraditional, or nondrug interventions to reduce pain, the guideline recommends a number of options including capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis. Ginkgo biloba, exercise, mindfulness, cognitive-behavioral therapy, and tai chi are also suggested.

“It is important to note that the recommended drugs and topical treatments in this guideline may not eliminate pain, but they have been shown to reduce pain,” Dr. Callaghan said. “The good news is there are many treatment options for painful diabetic neuropathy, so a treatment plan can be tailored specifically to each person living with this condition.”

Along with the updated guideline, the AAN has also published a new Polyneuropathy Quality Measurement Set to assist neurologists and other health care providers in treating patients with painful diabetic neuropathy.

The updated guideline was developed with financial support from the AAN.

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

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

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

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

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

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

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

As a physician first and a mental health clinician second, I hope to provide factual medical information on the Omicron variant to my patients, family members, and friends. I also try to remain curious instead of angry about why some choose not to vaccinate.

The most effective way to encourage people to obtain a vaccination is to use communication free of judgment and criticism, which allows a safe space for the unvaccinated to express their motivations and fears behind their current choice of not vaccinating and explore possible barriers to an alternative option that could lead to vaccination.

As an adult psychiatrist, ADHD specialist, and amateur COVID-19 expert, I’d like to offer 10 reasons why Omicron – which ironically means “small” in Latin, can still cause big destruction. Please share these 10 reasons with your patients.

• If you are not vaccinated, this virus will find you within the next few weeks and likely lead to severe symptoms.
• Long-haul symptoms from COVID-19 infection are still possible even for people who contract a milder case of the Omicron variant.
• The monoclonal antibody and antiviral treatments recently approved by the Food and Drug Administration for pre-exposure prevention of COVID-19 are limited. For many reasons, now is not the best time to play Russian roulette and intentionally get infected with a “mild” variant.
• There are not enough testing sites or over-the-counter rapid COVID tests available to keep up with the demand, and the latter are cost prohibitive for many people.
• Emergency care during the next few weeks for unforeseen non–COVID-related illnesses, such as a sudden heart attack or stroke, may be affected by the shortage of medical providers because of illness, quarantine, and burnout.
• There will be fewer first responders, including EMTs, police officers, and firefighters, because of COVID quarantines from illness and exposure.
• Although most Americans oppose temporary shutdowns, de facto shutdowns might be necessary because of the absence of healthy, COVID-negative individuals to maintain a functional society.
• Omicron math is deceiving, since the risk of hospitalization with Omicron appears to be far lower than with the Delta variant. However, the higher volume of infections with Omicron will offset the lower severity leading to comparable numbers of hospitalizations.
• Omicron has made it difficult for some schools to reopen after the holiday break, and reopening might become even more difficult as the surge progresses. Many schools already were in desperate need of substitute teachers, bus drivers, and additional staff necessary for COVID safety precautions before the emergence of the Omicron variant.
• And, for a less altruistic reason, as if the nine reasons above weren’t enough – if infections continue, especially among the unvaccinated – where the virus mutates the most – this can lead to a trifecta variant that not only evades the immune system and is highly infectious but causes severe disease in both the unvaccinated as well as the vaccinated.

Because of its extremely high transmissibility, the Omicron variant – layered atop Delta – presents great risk to us as a society. We must do all we can as clinicians to educate our patients so that they can protect themselves and their families.

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

As a physician first and a mental health clinician second, I hope to provide factual medical information on the Omicron variant to my patients, family members, and friends. I also try to remain curious instead of angry about why some choose not to vaccinate.

The most effective way to encourage people to obtain a vaccination is to use communication free of judgment and criticism, which allows a safe space for the unvaccinated to express their motivations and fears behind their current choice of not vaccinating and explore possible barriers to an alternative option that could lead to vaccination.

As an adult psychiatrist, ADHD specialist, and amateur COVID-19 expert, I’d like to offer 10 reasons why Omicron – which ironically means “small” in Latin, can still cause big destruction. Please share these 10 reasons with your patients.

• If you are not vaccinated, this virus will find you within the next few weeks and likely lead to severe symptoms.
• Long-haul symptoms from COVID-19 infection are still possible even for people who contract a milder case of the Omicron variant.
• The monoclonal antibody and antiviral treatments recently approved by the Food and Drug Administration for pre-exposure prevention of COVID-19 are limited. For many reasons, now is not the best time to play Russian roulette and intentionally get infected with a “mild” variant.
• There are not enough testing sites or over-the-counter rapid COVID tests available to keep up with the demand, and the latter are cost prohibitive for many people.
• Emergency care during the next few weeks for unforeseen non–COVID-related illnesses, such as a sudden heart attack or stroke, may be affected by the shortage of medical providers because of illness, quarantine, and burnout.
• There will be fewer first responders, including EMTs, police officers, and firefighters, because of COVID quarantines from illness and exposure.
• Although most Americans oppose temporary shutdowns, de facto shutdowns might be necessary because of the absence of healthy, COVID-negative individuals to maintain a functional society.
• Omicron math is deceiving, since the risk of hospitalization with Omicron appears to be far lower than with the Delta variant. However, the higher volume of infections with Omicron will offset the lower severity leading to comparable numbers of hospitalizations.
• Omicron has made it difficult for some schools to reopen after the holiday break, and reopening might become even more difficult as the surge progresses. Many schools already were in desperate need of substitute teachers, bus drivers, and additional staff necessary for COVID safety precautions before the emergence of the Omicron variant.
• And, for a less altruistic reason, as if the nine reasons above weren’t enough – if infections continue, especially among the unvaccinated – where the virus mutates the most – this can lead to a trifecta variant that not only evades the immune system and is highly infectious but causes severe disease in both the unvaccinated as well as the vaccinated.

Because of its extremely high transmissibility, the Omicron variant – layered atop Delta – presents great risk to us as a society. We must do all we can as clinicians to educate our patients so that they can protect themselves and their families.

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

As a physician first and a mental health clinician second, I hope to provide factual medical information on the Omicron variant to my patients, family members, and friends. I also try to remain curious instead of angry about why some choose not to vaccinate.

The most effective way to encourage people to obtain a vaccination is to use communication free of judgment and criticism, which allows a safe space for the unvaccinated to express their motivations and fears behind their current choice of not vaccinating and explore possible barriers to an alternative option that could lead to vaccination.

As an adult psychiatrist, ADHD specialist, and amateur COVID-19 expert, I’d like to offer 10 reasons why Omicron – which ironically means “small” in Latin, can still cause big destruction. Please share these 10 reasons with your patients.

• If you are not vaccinated, this virus will find you within the next few weeks and likely lead to severe symptoms.
• Long-haul symptoms from COVID-19 infection are still possible even for people who contract a milder case of the Omicron variant.
• The monoclonal antibody and antiviral treatments recently approved by the Food and Drug Administration for pre-exposure prevention of COVID-19 are limited. For many reasons, now is not the best time to play Russian roulette and intentionally get infected with a “mild” variant.
• There are not enough testing sites or over-the-counter rapid COVID tests available to keep up with the demand, and the latter are cost prohibitive for many people.
• Emergency care during the next few weeks for unforeseen non–COVID-related illnesses, such as a sudden heart attack or stroke, may be affected by the shortage of medical providers because of illness, quarantine, and burnout.
• There will be fewer first responders, including EMTs, police officers, and firefighters, because of COVID quarantines from illness and exposure.
• Although most Americans oppose temporary shutdowns, de facto shutdowns might be necessary because of the absence of healthy, COVID-negative individuals to maintain a functional society.
• Omicron math is deceiving, since the risk of hospitalization with Omicron appears to be far lower than with the Delta variant. However, the higher volume of infections with Omicron will offset the lower severity leading to comparable numbers of hospitalizations.
• Omicron has made it difficult for some schools to reopen after the holiday break, and reopening might become even more difficult as the surge progresses. Many schools already were in desperate need of substitute teachers, bus drivers, and additional staff necessary for COVID safety precautions before the emergence of the Omicron variant.
• And, for a less altruistic reason, as if the nine reasons above weren’t enough – if infections continue, especially among the unvaccinated – where the virus mutates the most – this can lead to a trifecta variant that not only evades the immune system and is highly infectious but causes severe disease in both the unvaccinated as well as the vaccinated.

Because of its extremely high transmissibility, the Omicron variant – layered atop Delta – presents great risk to us as a society. We must do all we can as clinicians to educate our patients so that they can protect themselves and their families.

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

Atopic dermatitis (AD) may be especially active and severe among older adults, and it may be associated with increased risk of comorbid conditions common in later stages of life, including osteoporosis, dementia, and cardiovascular disease.

During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.

“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.

In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).

“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”

In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.

To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”

In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”

According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).

In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”

In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.

Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.

She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.

[email protected]

Atopic dermatitis (AD) may be especially active and severe among older adults, and it may be associated with increased risk of comorbid conditions common in later stages of life, including osteoporosis, dementia, and cardiovascular disease.

During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.

“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.

In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).

“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”

In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.

To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”

In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”

According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).

In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”

In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.

Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.

She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.

[email protected]

Atopic dermatitis (AD) may be especially active and severe among older adults, and it may be associated with increased risk of comorbid conditions common in later stages of life, including osteoporosis, dementia, and cardiovascular disease.

During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.

“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.

In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).

“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”

In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.

To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”

In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”

According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).

In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”

In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.

Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.

She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.

[email protected]

A new meta-analysis suggests the risk for violence is higher in patients with schizophrenia, but some experts beg to differ, calling out study limitations and urging caution when interpreting the findings.

The study suggests patients with schizophrenia spectrum disorder (SSD) are 4.5 times more likely than individuals in the general population to perpetrate violence against others.

While the results showed comorbid substance misuse was associated with a significantly increased risk for violence in those with SSD, data on medication nonadherence, prior exposure to violence, childhood trauma, or other known risk factors were not included in the study.

“I think one of the main implications of this study is that prevention of violence outcomes really should be a focus for clinical services, because these are important outcomes to prevent and many of the factors that increase risk are modifiable, such as substance misuse and treatment adherence,” study coinvestigator Seena Fazel, MD, professor of forensic psychiatry at the University of Oxford (England), said in an interview.

Still, some experts urge caution when interpreting the findings, which they fear could perpetuate stigma against individuals with serious mental illness if not taken in the context of a study that shows association, not causation.

“While potential for violence is certainly a relevant consideration in assessing persons with schizophrenia spectrum disorder, it would be wrong to conclude from this study that schizophrenia spectrum disorders per se cause people to become violent,” said Ronald W. Pies, MD, professor emeritus of psychiatry at the State University of New York, Syracuse, who commented on the findings.

The findings were published online Dec. 22, 2021, in JAMA Psychiatry.
 

No causal link

The meta-analysis included 24 studies involving 51,309 individuals with SSD from 15 countries over 4 decades.

Risk for violence perpetrated by men with schizophrenia was 4.5 times higher (95% confidence interval, 3.6-5.6) than their counterparts in the general population. Among women, the rate was 10.2 times higher (95% CI, 7.1-14.6) versus those without SSD.

The odds of perpetrating sexual offenses (odds ratio, 5.1; 95% CI, 3.8-6.8) and homicide (OR, 17.7; 95% CI, 13.9-22.6) were also increased.

When restricting analysis to studies that used outcomes only from register-based sources, indicating a criminal arrest or conviction, absolute risks of violence perpetration ranged from 2.3% to 24.7% in men with SSD and from 0% to 5.4% in women up to a 35-year follow-up.

“That means that over a 35-year period most men are not going to be involved in these criminal register-based violent outcomes,” Dr. Fazel said. “And at least 90% of the women are not going to have any register-based violent outcomes.”

When accounting for substance use comorbidity, risk for violence perpetration dropped sharply. Those with no substance misuse were 3.5 times more likely than those in the general population to commit acts of violence versus 9.9 times in those with substance misuse comorbidity.

“In these subgroup studies of people with dual diagnoses of schizophrenia and substance misuse, the risk was increased 10-fold,” Dr. Fazel said. “If you look at people without substance misuse comorbidity, there remains a risk there of between three- to fourfold increase. It doesn’t explain the association completely.”

The investigators were quick to point out that this new study identifies an association between SSD and violence, and not causation.

“One important way to consider the association is to think of clinical services for people presenting with a schizophrenia spectrum disorder: Does the evidence suggest that violence is an important enough potential adverse outcome, for a minority of those individuals, such that support for this clinical need should be improved?” study investigator Daniel Whiting, BM BCh, a doctoral research fellow in psychiatry at the University of Oxford, said in an interview. “We highlight this as an implication of the findings.”

Whether the association would change if researchers controlled for substance misuse in both the study and control groups is unknown. Also unclear from this study is what impact other risk factors may have on increasing violent outcomes in individuals with SSD.
 

Education, treatment adherence important

Dr. Pies pointed out that, “notably, the risk for violence in the study population declined more than sixfold when comorbid substance abuse was excluded from the analysis.”

That aligns with an earlier study conducted in Sweden by Dr. Fazel, which showed that, after controlling for substance misuse, the rate of violent crime among individuals with schizophrenia was only slightly higher than in the general population.

“The fact is that people with schizophrenia who are compliant with proper medication do not commit violent acts any more than those in the general population,” Lynn DeLisi, MD, professor of psychiatry at Harvard Medical School, Boston, and founding editor of Schizophrenia Research, said in a comment.

Indeed, Dr. Fazel’s own research suggests treatment with antipsychotics cuts in half the risk for violent crime by patients with severe mental illness.

“The goal should be education of school officials, families, and primary care physicians to detect this illness early and treat it. Programs that make sure patients comply with medication once they begin it are equally important,” Dr. DeLisi said.

Treatment adherence is important, but the first step toward violence prevention is high-quality risk assessment, said Dr. Fazel. His research team has developed a web-based, free risk calculator shown to help clinicians evaluate the risk that a patient might become violent.

Dr. Pies agreed with the importance of comprehensive, clinical assessments of modifiable risk factors, including substance use, homelessness, medication adherence, and conflictual relationships.

This kind of assessment, “in my experience, is rarely carried out in most evaluations of persons with psychotic symptoms or SSD,” he said.
 

Perpetuating stigma?

Another concern raised by Dr. Pies and Dr. DeLisi is how the findings might perpetuate stigma toward individuals with serious mental illness. Results from a recently published study showed that, although attitudes toward those with major depression have improved in the United States over the past few decades, stigma toward those with schizophrenia has actually worsened.

The most effective approach to reducing stigma is to “face up to the evidence, then try and prevent the negative outcomes,” Dr. Fazel said.

“The conclusion of this paper is that it’s all pointing toward a strategy toward prevention by developing high-quality risk assessment and then developing high-quality treatment programs that include not just pharmacological treatments but psychosocial treatments and beyond,” he added. “We know that’s the way it works for other disorders as well.”

Although mental illness stigma is a serious problem, Dr. Pies noted, “the risk is not so much that studies of this sort are carried out and then covered in the media, but that they are decontextualized and reduced to ‘bumper sticker’ headlines.”

“The public needs context and perspective,” he said. “It needs to be informed that violent behavior is relatively rare among persons with psychiatric illness, including persons with schizophrenia and related disorders who do not also have a substance use disorder.”

Indeed, some studies have shown that individuals with mental illness are more often the victims of violence than the perpetrators.

“Frankly, the public is much more at risk from the neighborhood lout who drinks heavily and repeatedly starts bar fights than from the average patient with a schizophrenia spectrum disorder,” Dr. Pies said.

Dr. Fazel reported receiving funding from the Wellcome Trust. Dr. DeLisi and Dr. Pies disclosed no relevant financial relationships.

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

A new meta-analysis suggests the risk for violence is higher in patients with schizophrenia, but some experts beg to differ, calling out study limitations and urging caution when interpreting the findings.

The study suggests patients with schizophrenia spectrum disorder (SSD) are 4.5 times more likely than individuals in the general population to perpetrate violence against others.

While the results showed comorbid substance misuse was associated with a significantly increased risk for violence in those with SSD, data on medication nonadherence, prior exposure to violence, childhood trauma, or other known risk factors were not included in the study.

“I think one of the main implications of this study is that prevention of violence outcomes really should be a focus for clinical services, because these are important outcomes to prevent and many of the factors that increase risk are modifiable, such as substance misuse and treatment adherence,” study coinvestigator Seena Fazel, MD, professor of forensic psychiatry at the University of Oxford (England), said in an interview.

Still, some experts urge caution when interpreting the findings, which they fear could perpetuate stigma against individuals with serious mental illness if not taken in the context of a study that shows association, not causation.

“While potential for violence is certainly a relevant consideration in assessing persons with schizophrenia spectrum disorder, it would be wrong to conclude from this study that schizophrenia spectrum disorders per se cause people to become violent,” said Ronald W. Pies, MD, professor emeritus of psychiatry at the State University of New York, Syracuse, who commented on the findings.

The findings were published online Dec. 22, 2021, in JAMA Psychiatry.
 

No causal link

The meta-analysis included 24 studies involving 51,309 individuals with SSD from 15 countries over 4 decades.

Risk for violence perpetrated by men with schizophrenia was 4.5 times higher (95% confidence interval, 3.6-5.6) than their counterparts in the general population. Among women, the rate was 10.2 times higher (95% CI, 7.1-14.6) versus those without SSD.

The odds of perpetrating sexual offenses (odds ratio, 5.1; 95% CI, 3.8-6.8) and homicide (OR, 17.7; 95% CI, 13.9-22.6) were also increased.

When restricting analysis to studies that used outcomes only from register-based sources, indicating a criminal arrest or conviction, absolute risks of violence perpetration ranged from 2.3% to 24.7% in men with SSD and from 0% to 5.4% in women up to a 35-year follow-up.

“That means that over a 35-year period most men are not going to be involved in these criminal register-based violent outcomes,” Dr. Fazel said. “And at least 90% of the women are not going to have any register-based violent outcomes.”

When accounting for substance use comorbidity, risk for violence perpetration dropped sharply. Those with no substance misuse were 3.5 times more likely than those in the general population to commit acts of violence versus 9.9 times in those with substance misuse comorbidity.

“In these subgroup studies of people with dual diagnoses of schizophrenia and substance misuse, the risk was increased 10-fold,” Dr. Fazel said. “If you look at people without substance misuse comorbidity, there remains a risk there of between three- to fourfold increase. It doesn’t explain the association completely.”

The investigators were quick to point out that this new study identifies an association between SSD and violence, and not causation.

“One important way to consider the association is to think of clinical services for people presenting with a schizophrenia spectrum disorder: Does the evidence suggest that violence is an important enough potential adverse outcome, for a minority of those individuals, such that support for this clinical need should be improved?” study investigator Daniel Whiting, BM BCh, a doctoral research fellow in psychiatry at the University of Oxford, said in an interview. “We highlight this as an implication of the findings.”

Whether the association would change if researchers controlled for substance misuse in both the study and control groups is unknown. Also unclear from this study is what impact other risk factors may have on increasing violent outcomes in individuals with SSD.
 

Education, treatment adherence important

Dr. Pies pointed out that, “notably, the risk for violence in the study population declined more than sixfold when comorbid substance abuse was excluded from the analysis.”

That aligns with an earlier study conducted in Sweden by Dr. Fazel, which showed that, after controlling for substance misuse, the rate of violent crime among individuals with schizophrenia was only slightly higher than in the general population.

“The fact is that people with schizophrenia who are compliant with proper medication do not commit violent acts any more than those in the general population,” Lynn DeLisi, MD, professor of psychiatry at Harvard Medical School, Boston, and founding editor of Schizophrenia Research, said in a comment.

Indeed, Dr. Fazel’s own research suggests treatment with antipsychotics cuts in half the risk for violent crime by patients with severe mental illness.

“The goal should be education of school officials, families, and primary care physicians to detect this illness early and treat it. Programs that make sure patients comply with medication once they begin it are equally important,” Dr. DeLisi said.

Treatment adherence is important, but the first step toward violence prevention is high-quality risk assessment, said Dr. Fazel. His research team has developed a web-based, free risk calculator shown to help clinicians evaluate the risk that a patient might become violent.

Dr. Pies agreed with the importance of comprehensive, clinical assessments of modifiable risk factors, including substance use, homelessness, medication adherence, and conflictual relationships.

This kind of assessment, “in my experience, is rarely carried out in most evaluations of persons with psychotic symptoms or SSD,” he said.
 

Perpetuating stigma?

Another concern raised by Dr. Pies and Dr. DeLisi is how the findings might perpetuate stigma toward individuals with serious mental illness. Results from a recently published study showed that, although attitudes toward those with major depression have improved in the United States over the past few decades, stigma toward those with schizophrenia has actually worsened.

The most effective approach to reducing stigma is to “face up to the evidence, then try and prevent the negative outcomes,” Dr. Fazel said.

“The conclusion of this paper is that it’s all pointing toward a strategy toward prevention by developing high-quality risk assessment and then developing high-quality treatment programs that include not just pharmacological treatments but psychosocial treatments and beyond,” he added. “We know that’s the way it works for other disorders as well.”

Although mental illness stigma is a serious problem, Dr. Pies noted, “the risk is not so much that studies of this sort are carried out and then covered in the media, but that they are decontextualized and reduced to ‘bumper sticker’ headlines.”

“The public needs context and perspective,” he said. “It needs to be informed that violent behavior is relatively rare among persons with psychiatric illness, including persons with schizophrenia and related disorders who do not also have a substance use disorder.”

Indeed, some studies have shown that individuals with mental illness are more often the victims of violence than the perpetrators.

“Frankly, the public is much more at risk from the neighborhood lout who drinks heavily and repeatedly starts bar fights than from the average patient with a schizophrenia spectrum disorder,” Dr. Pies said.

Dr. Fazel reported receiving funding from the Wellcome Trust. Dr. DeLisi and Dr. Pies disclosed no relevant financial relationships.

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

A new meta-analysis suggests the risk for violence is higher in patients with schizophrenia, but some experts beg to differ, calling out study limitations and urging caution when interpreting the findings.

The study suggests patients with schizophrenia spectrum disorder (SSD) are 4.5 times more likely than individuals in the general population to perpetrate violence against others.

While the results showed comorbid substance misuse was associated with a significantly increased risk for violence in those with SSD, data on medication nonadherence, prior exposure to violence, childhood trauma, or other known risk factors were not included in the study.

“I think one of the main implications of this study is that prevention of violence outcomes really should be a focus for clinical services, because these are important outcomes to prevent and many of the factors that increase risk are modifiable, such as substance misuse and treatment adherence,” study coinvestigator Seena Fazel, MD, professor of forensic psychiatry at the University of Oxford (England), said in an interview.

Still, some experts urge caution when interpreting the findings, which they fear could perpetuate stigma against individuals with serious mental illness if not taken in the context of a study that shows association, not causation.

“While potential for violence is certainly a relevant consideration in assessing persons with schizophrenia spectrum disorder, it would be wrong to conclude from this study that schizophrenia spectrum disorders per se cause people to become violent,” said Ronald W. Pies, MD, professor emeritus of psychiatry at the State University of New York, Syracuse, who commented on the findings.

The findings were published online Dec. 22, 2021, in JAMA Psychiatry.
 

No causal link

The meta-analysis included 24 studies involving 51,309 individuals with SSD from 15 countries over 4 decades.

Risk for violence perpetrated by men with schizophrenia was 4.5 times higher (95% confidence interval, 3.6-5.6) than their counterparts in the general population. Among women, the rate was 10.2 times higher (95% CI, 7.1-14.6) versus those without SSD.

The odds of perpetrating sexual offenses (odds ratio, 5.1; 95% CI, 3.8-6.8) and homicide (OR, 17.7; 95% CI, 13.9-22.6) were also increased.

When restricting analysis to studies that used outcomes only from register-based sources, indicating a criminal arrest or conviction, absolute risks of violence perpetration ranged from 2.3% to 24.7% in men with SSD and from 0% to 5.4% in women up to a 35-year follow-up.

“That means that over a 35-year period most men are not going to be involved in these criminal register-based violent outcomes,” Dr. Fazel said. “And at least 90% of the women are not going to have any register-based violent outcomes.”

When accounting for substance use comorbidity, risk for violence perpetration dropped sharply. Those with no substance misuse were 3.5 times more likely than those in the general population to commit acts of violence versus 9.9 times in those with substance misuse comorbidity.

“In these subgroup studies of people with dual diagnoses of schizophrenia and substance misuse, the risk was increased 10-fold,” Dr. Fazel said. “If you look at people without substance misuse comorbidity, there remains a risk there of between three- to fourfold increase. It doesn’t explain the association completely.”

The investigators were quick to point out that this new study identifies an association between SSD and violence, and not causation.

“One important way to consider the association is to think of clinical services for people presenting with a schizophrenia spectrum disorder: Does the evidence suggest that violence is an important enough potential adverse outcome, for a minority of those individuals, such that support for this clinical need should be improved?” study investigator Daniel Whiting, BM BCh, a doctoral research fellow in psychiatry at the University of Oxford, said in an interview. “We highlight this as an implication of the findings.”

Whether the association would change if researchers controlled for substance misuse in both the study and control groups is unknown. Also unclear from this study is what impact other risk factors may have on increasing violent outcomes in individuals with SSD.
 

Education, treatment adherence important

Dr. Pies pointed out that, “notably, the risk for violence in the study population declined more than sixfold when comorbid substance abuse was excluded from the analysis.”

That aligns with an earlier study conducted in Sweden by Dr. Fazel, which showed that, after controlling for substance misuse, the rate of violent crime among individuals with schizophrenia was only slightly higher than in the general population.

“The fact is that people with schizophrenia who are compliant with proper medication do not commit violent acts any more than those in the general population,” Lynn DeLisi, MD, professor of psychiatry at Harvard Medical School, Boston, and founding editor of Schizophrenia Research, said in a comment.

Indeed, Dr. Fazel’s own research suggests treatment with antipsychotics cuts in half the risk for violent crime by patients with severe mental illness.

“The goal should be education of school officials, families, and primary care physicians to detect this illness early and treat it. Programs that make sure patients comply with medication once they begin it are equally important,” Dr. DeLisi said.

Treatment adherence is important, but the first step toward violence prevention is high-quality risk assessment, said Dr. Fazel. His research team has developed a web-based, free risk calculator shown to help clinicians evaluate the risk that a patient might become violent.

Dr. Pies agreed with the importance of comprehensive, clinical assessments of modifiable risk factors, including substance use, homelessness, medication adherence, and conflictual relationships.

This kind of assessment, “in my experience, is rarely carried out in most evaluations of persons with psychotic symptoms or SSD,” he said.
 

Perpetuating stigma?

Another concern raised by Dr. Pies and Dr. DeLisi is how the findings might perpetuate stigma toward individuals with serious mental illness. Results from a recently published study showed that, although attitudes toward those with major depression have improved in the United States over the past few decades, stigma toward those with schizophrenia has actually worsened.

The most effective approach to reducing stigma is to “face up to the evidence, then try and prevent the negative outcomes,” Dr. Fazel said.

“The conclusion of this paper is that it’s all pointing toward a strategy toward prevention by developing high-quality risk assessment and then developing high-quality treatment programs that include not just pharmacological treatments but psychosocial treatments and beyond,” he added. “We know that’s the way it works for other disorders as well.”

Although mental illness stigma is a serious problem, Dr. Pies noted, “the risk is not so much that studies of this sort are carried out and then covered in the media, but that they are decontextualized and reduced to ‘bumper sticker’ headlines.”

“The public needs context and perspective,” he said. “It needs to be informed that violent behavior is relatively rare among persons with psychiatric illness, including persons with schizophrenia and related disorders who do not also have a substance use disorder.”

Indeed, some studies have shown that individuals with mental illness are more often the victims of violence than the perpetrators.

“Frankly, the public is much more at risk from the neighborhood lout who drinks heavily and repeatedly starts bar fights than from the average patient with a schizophrenia spectrum disorder,” Dr. Pies said.

Dr. Fazel reported receiving funding from the Wellcome Trust. Dr. DeLisi and Dr. Pies disclosed no relevant financial relationships.

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

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.