PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

egreb@mdedge.com

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

egreb@mdedge.com

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

PHILADELPHIA – In patients with migraine and medication overuse, galcanezumab reduces the number of mean monthly migraine headache days, according to research presented at the annual meeting of the American Headache Society. Furthermore, galcanezumab is associated with a reduction in medication overuse, compared with placebo, in this population.

“When you have targeted preventive treatment and you reduce the burden of illness, medication overuse seems to be reduced as well,” said Sheena Aurora, MD, adjunct clinical associate professor of anesthesiology and perioperative and pain medicine at Stanford (Calif.) Health Care. Dr. Aurora also is a medical fellow and global launch leader for galcanezumab at Eli Lilly, which has developed the treatment.

Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide. The phase 3 EVOLVE-1, EVOLVE-2, and REGAIN studies indicated galcanezumab’s superiority to placebo in preventing episodic and chronic migraine.
 

A post hoc analysis of phase 3 data

Dr. Aurora and colleagues conducted a post hoc analysis of data from the three phase 3 studies to examine galcanezumab’s effect in patients with medication overuse. EVOLVE-1 and EVOLVE-2 included patients with episodic migraine, and REGAIN included patients with chronic migraine. All participants were randomized to monthly subcutaneous injections of placebo or galcanezumab (120 mg/month or 240 mg/month) for 3-6 months. Based on information obtained through electronic patient-reported outcome diaries, investigators determined headache medication overuse using criteria adapted from the International Classification of Headache Disorders, third edition. They estimated mean changes in monthly headache days and the proportion of patients with medication overuse after randomization using mixed modeling.

The demographic characteristics of the three study populations were similar to those reported in epidemiologic studies of migraine, said Dr. Aurora. Most participants were women, and most patients were between ages 40 and 49 years. At baseline, the mean number of monthly migraine headache days was 20 among patients with chronic migraine and 9 among patients with episodic migraine.

The rate of medication overuse was higher in the combined study population than in the literature. Patients with medication overuse had greater disability and greater health care resource utilization, compared with patients without medication overuse. Among patients with chronic migraine, participants who overused medication were not significantly different from those who did not. But among patients with episodic migraine, participants who overused medication had higher headache frequency than those who did not.

In the EVOLVE trials, the proportion of patients with baseline medication overuse was 19.3% in the placebo arm, 17.0% in the galcanezumab 120-mg arm, and 19.2% in the galcanezumab 240-mg arm. In REGAIN, the proportion of patients with baseline medication overuse was 63.4% in the placebo arm, 64.3% in the galcanezumab 120-mg arm, and 64.1% in the galcanezumab 240-mg arm.

Galcanezumab reduced medication overuse

Compared with placebo, both doses of galcanezumab significantly decreased mean monthly migraine headache days in patients with baseline medication overuse. In the EVOLVE studies, this endpoint decreased by 2.71 in the placebo group, 6.26 in the galcanezumab 120-mg group, and 5.77 in the galcanezumab 240-mg group. In REGAIN, the reductions were 2.25 in the placebo group, 4.78 in the galcanezumab 120-mg group, and 4.51 in the galcanezumab 240-mg group. The effect size was higher in patients who were overusing medications, compared with those who were not, said Dr. Aurora. “This is clinically relevant, because most of us ... had this belief that patients who were overusing medications may be more treatment-resistant to prevention.”

In addition, galcanezumab was associated with significantly lower rates of average monthly medication overuse, compared with placebo. In the EVOLVE studies, the average rate of monthly medication overuse was 15.9% for the placebo group, 6.2% for the galcanezumab 120-mg group, and 7.9% for the galcanezumab 240-mg group. In REGAIN, the average rate of monthly medication overuse was 40.6% in the placebo group, 24.3% in the galcanezumab 120-mg group, and 23.1% in the galcanezumab 240-mg group. About 85% of patients with episodic migraine and medication overuse had a reduction in medication overuse, and approximately 50% of patients with chronic migraine and medication overuse had a reduction in medication overuse, said Dr. Aurora.

Dr. Aurora and coinvestigators are employees of Eli Lilly, which developed galcanezumab and funded the EVOLVE and REGAIN studies.

egreb@mdedge.com

SOURCE: Aurora S et al. AHS 2019. Abstract IOR07.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

The patient was given a diagnosis of green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail. GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.

Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa can grow in these spaces. Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS, and it is typical for only one nail to be involved.

It’s likely that this patient’s earlier nail problem had been a case of onycholysis, based on her description of a “spongy” nail bed and loose nail. This created a favorable environment for an infection by allowing moisture and bacteria to infiltrate the space. The patient also acknowledged that she washed dishes by hand and bathed her young children. This frequent soaking of her hands likely helped to provide a moist environment in which P aeruginosa could thrive. In addition, onycholysis is associated with hypothyroidism, which the patient also had.

GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history. Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases. The specific shade of discoloration helps to differentiate the underlying pathology. Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected. GNS is often painless, but may be accompanied by mild tenderness of the nail.

The patient was prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (1 part bleach to 4 parts water) twice a day. She also was advised to wear gloves for household tasks that involved immersing her hands in water, and to dry her finger with a hair dryer after bathing.

‌

This case was adapted from: Gish D, Romero BJ. Green fingernail. J Fam Pract. 2017;66:E7-E9.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

Veterans with a clinically meaningful reduction in symptoms of PTSD are less likely to develop type 2 diabetes, research from a retrospective study shows.

“We cautiously speculate that normalization of hypothalamic-pituitary-adrenal axis and cortisol levels could be one mechanism behind our results,” wrote Jeffrey F. Scherrer, PhD, and colleagues. “PTSD is associated with inflammation, which may in turn be associated with increased risk for [type 2 diabetes].” The study was published in JAMA Psychiatry.

Using medical record data from the Veterans Health Administration, Dr. Scherrer and colleagues identified 5,916 patients with PTSD who visited a VHA medical center between 2008 and 2012, and scored at least 50 points or higher on the PTSD Checklist (PCL) followed by another PCL score at least 8 months after the previous score. The mean age of patients in the study was 42.1 years, the cohort consisted of 84.3% men, and 66.3% patients were white. PCL score reduction was deemed clinically meaningful if there was a decrease of 20 points or more in the score, reported Dr. Scherrer of the department of family and community medicine at Saint Louis University and colleagues.

Patients who were older (mean 43.6 years vs. mean 41.7 years; P = .02) and those who underwent minimally adequate duration of PTSD psychotherapy (P less than .001) were significantly more likely to have a clinically meaningful decrease in PCL scores. Patients who received antidepressants (P = .004) or antipsychotics (P less than .001) were significantly more likely to have less than clinically meaningful decreases in PCL scores. Factors that put patients at significantly higher risk of developing type 2 diabetes included older age (hazard ratio, 1.05; 95% confidence interval, 1.04-1.07; P less than .001), black race/ethnicity (HR, 1.86; 95% CI, 1.23-2.83; P = .004), hypertension (HR, 3.46; 95% CI, 2.33-5.16), hyperlipidemia (HR, 2.82; 95% CI, 1.91-4.16), and obesity (HR, 3.32; 95% CI, 2.12-5.21) (all P less than .001).

Minimally adequate duration of PTSD psychotherapy and high use of primary care health services also were associated with developing type 2 diabetes.

In a Cox proportional hazards regression model, patients with clinically meaningful decreases in PCL scores had significantly lower risk of developing type 2 diabetes, and those results remained consistent after adjusting for age, calculating the results using weighted data, and factoring in hypertension, obesity, and hyperlipidemia.

“This result was independent of numerous demographics and psychiatric and physical comorbidities,” said Dr. Scherrer and colleagues. “The association was also independent of the number of PTSD psychotherapy sessions used, suggesting that a healthy adherer effect, or a general orientation to improve health, is unlikely to explain our observations.”

Dr. Scherrer and colleagues cited several limitations, such as unmeasured confounding and the difficulty of generalizing the results beyond PTSD patients in a VHA setting. In addition, the researchers were unable to calculate the lifetime effect of reduced PTSD symptoms and incidence of type 2 diabetes.

This study was funded in part by a grant from the National Heart, Lung, and Blood Institute. Four authors reported receiving one or more grants from the National Heart, Lung, and Blood Institute during the study period. Some authors reported receiving other support from Noblis Therapeutics and Saint Louis University both during and outside the study period. The other authors reported no relevant conflicts of interest.

SOURCE: Scherrer JF et al. JAMA Psychiatry. 2019 Aug 21. doi: 10.1001/jamapsychiatry.2019.2096.

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

dfulton@mdedge.com

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

dfulton@mdedge.com

More than 150 cases of severe lung illness possibly related to e-cigarette use in adolescents and young adults have been reported in 16 states, according to an Aug. 21 update from officials at the Centers for Disease Control and Prevention.

licsiren/iStock/Getty Images

Officials from the CDC and the Food and Drug Administration are working with state health officials to gather information on the cases as well as any products or substances that might be involved.

A total of 153 potential cases were reported between June 28 and Aug. 20 in 16 states – California, Connecticut, Florida, Illinois, Indiana, Iowa, Michigan, Minnesota, New Jersey, New Mexico, New York, North Carolina, Pennsylvania, Texas, Utah, and Wisconsin.

Health officials have yet to find a cause for these illnesses; however, all patients have reported e-cigarette use or vaping, according to a CDC statement. Evidence to date does not seem to indicate that an infectious agent is the cause.

In general, patients have reported a gradual onset of symptoms including shortness of breath and/or chest pain that increased over days or weeks before hospital admission. Gastrointestinal symptoms including vomiting, diarrhea, and fatigue have been reported by some.

Many patients reported using products containing tetrahydrocannabinol, though no specific or consistent product has been linked definitively.

While cases reported across the country seem to be similar, there is no evidence currently indicating they have a common cause, according to the CDC statement.

The CDC is urging health care professionals to report possible cases to their state or local health department and the FDA is urging the public to provide detailed reports of any unusual or unexpected health concerns related to tobacco use or e-cigarette use through its Safety Reporting Portal.

dfulton@mdedge.com

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Regardless of where people live in the world, air pollution is linked to increased rates of cardiovascular disease, respiratory problems, and all-cause mortality, according to one of the largest studies ever to assess the effects of inhalable particulate matter (PM), published Aug. 21 in the New England Journal of Medicine.

“These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies,” reported Cong Liu of the Huazhong University of Science and Technology in Wuhan, China, and an international team of researchers.

“Many people are experiencing worse allergy and asthma symptoms in the setting of increased heat and worse air quality,” Caren G. Solomon, MD, of Harvard Medical School, Boston, said in an interview. “It is often not appreciated that these are complications of climate change.”

Other such complications include heat-related illnesses and severe weather events, as well as the less visible manifestations, such as shifts in the epidemiology of vector-borne infectious disease, Dr. Solomon and colleagues wrote in an editorial accompanying Mr. Liu’s study.

“The stark reality is that high levels of greenhouse gases caused by the combustion of fossil fuels – and the resulting rise in temperature and sea levels and intensification of extreme weather – are having profound consequences for human health and health systems,” Dr. Solomon and colleagues wrote (N Engl J Med. 2019;381:773-4.).

In the new air pollution study, Mr. Liu and colleagues analyzed 59.6 million deaths from 652 cities across 24 countries, “thereby greatly increasing the generalizability of the association and decreasing the likelihood that the reported associations are subject to confounding bias,” wrote John R. Balmes, MD, of the University of California, San Francisco, and the University of California, Berkeley, in an editorial about the study (N Engl J Med. 2019;381:774-6).

The researchers compared air pollution data from 1986-2015 from the Multi-City Multi-Country (MCC) Collaborative Research Network to mortality data reported from individual countries. They assessed PM with an aerodynamic diameter of 10 mcg or less (PM10; n = 598 cities) and PM with an aerodynamic diameter of 2.5 mcg or less (PM_2.5; n=499 cities).

Mr. Liu’s team used a time-series analysis – a standard upon which the majority of air pollution research relies. These studies “include daily measures of health events (e.g., daily mortality), regressed against concentrations of PM (e.g., 24-hour average PM_2.5) and weather variables (e.g., daily average temperature) for a given geographic area,” Dr. Balmes wrote. “The population serves as its own control, and confounding by population characteristics is negligible because these are stable over short time frames.”

The researchers found a 0.44% increase in daily all-cause mortality for each 10-mcg/m³ increase in the 2-day moving average (current and previous day) of PM₁₀. The same increase was linked to a 0.36% increase in daily cardiovascular mortality and a 0.47% increase in daily respiratory mortality. Similarly, a 10-mcg/m³ increase in the PM_2.5 average was linked to 0.68% increase in all-cause mortality, a 0.55% increase in cardiovascular mortality, and 0.74% increase in respiratory mortality.

Locations with higher annual mean temperatures showed stronger associations, and all these associations remained statistically significant after the researchers adjusted for gaseous pollutants.

Although the majority of countries and cities included in the study came from the northern hemisphere, the researchers noted that the magnitude of effect they found, particularly for PM₁₀ concentrations, matched up with that seen in previous studies of multiple cities or countries.

Still, they found “significant evidence of spatial heterogeneity in the associations between PM concentration and daily mortality across countries and regions.” Among the factors that could contribute to those variations are “different PM components, long-term air pollution levels, population susceptibility, and different lengths of study periods,” they speculated.

What makes this study remarkable – despite decades of previous similar studies – is its size and the implications of a curvilinear shape in its concentration-response relation, according to Dr. Balmes.

“The current study of PM data from many regions around the world provides the strongest evidence to date that higher levels of exposure may be associated with a lower per-unit risk,” Dr. Balmes wrote. “Regions that have lower exposures had a higher per-unit risk. This finding has profound policy implications, especially given that no threshold of effect was found. Even high-income countries, such as the United States, with relatively good air quality could still see public health benefits from further reduction of ambient PM concentrations.”

The policy implications, however, extend well beyond clean air regulations because the findings represent just one aspect of climate change’s negative effects on health, which are “frighteningly broad,” Dr. Solomon and colleagues wrote.

“As climate change continues to alter disease patterns and disrupt health systems, its effects on human health will become harder to ignore,” they wrote. “We, as a medical community, have the responsibility and the opportunity to mobilize the urgent, large-scale climate action required to protect health – as well as the ingenuity to develop novel and bold interventions to avert the most catastrophic outcomes.”

The new research and associated commentary marked the introduction of a new NEJM topic on climate change effects on health and health systems.
 

SOURCE: Liu C et al. N Engl J Med. 2019;381:705-15.

This article was updated 8/22/19.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

Selinexor plus low-dose dexamethasone can produce responses in patients with triple-class refractory multiple myeloma, according to the phase 2 STORM trial.

Wikimedia Commons/KGH/Creative Commons License

The combination produced a response rate of 26% in patients who were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab.

The most common grade 3/4 adverse events in this trial were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%).

Ajai Chari, MD, of the Mount Sinai School of Medicine, New York, and colleagues reported these results in the New England Journal of Medicine.

The STORM trial included 123 patients with multiple myeloma who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent. Their disease was refractory to at least one proteasome inhibitor, one immunomodulatory drug, and daratumumab.

The patients had received a median of 7 (range, 3-18) prior treatment regimens, and their median time since diagnosis was 6.6 years (range, 1.1-23.4 years). The median age at baseline was 65.2 years (range, 40-86 years), 58% of patients were men, and 53% had high-risk cytogenetics. In addition, 36% of patients had thrombocytopenia and 16% had neutropenia at baseline.

The patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression, death, or discontinuation. Doses were modified in response to adverse events.

Results

In total, 96% of patients (118/123) discontinued treatment. The most common reasons for discontinuation were disease progression (n = 65) and adverse events (n = 38).

Of the 122 patients evaluable for efficacy, 26% achieved a partial response or better, and 39% had a minimal response or better. There were 24 partial responses, 16 minimal responses, 6 very good partial responses, and 2 stringent complete responses. Forty-eight patients had stable disease.

The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The median overall survival was 15.6 months in responders, 5.9 months in patients with stable disease, and 1.7 months in those who progressed.

All 123 patients were evaluable for safety, and 63% of them experienced serious adverse events. Pneumonia (11%) and sepsis (9%) were the most common serious events.

The most common treatment-emergent nonhematologic adverse events were fatigue (73%), nausea (72%), decreased appetite (56%), decreased weight (50%), diarrhea (46%), vomiting (38%), hyponatremia (37%), upper respiratory tract infection (23%), constipation (22%), and dyspnea (22%).

Treatment-emergent hematologic adverse events included thrombocytopenia (73%), anemia (67%), neutropenia (40%), leukopenia (33%), and lymphopenia (16%).

Eighty percent of patients had adverse events leading to dose modification or interruption. The most common of these were thrombocytopenia (43%), fatigue (16%), and neutropenia (11%).

“Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol,” the researchers wrote.


“The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia … was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.”

There were 28 deaths on study, with 16 patients dying of disease progression and 12 dying from an adverse event. Two of the fatal adverse events were considered treatment related – sepsis in one patient and pneumonia with concurrent disease progression in another patient.

The researchers reported ties with Karyopharm Therapeutics, which sponsored the study, and many other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. N Engl J Med 2019;381:727-38.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.

This supplement to Neurology Reviews compiles MS-related news briefs from the 2019 annual meetings the American Academy of Neurology, held in Philadelphia in early May, and the Consortium of Multiple Sclerosis Centers, held in Seattle in late May.  

Click here to read the supplement.

Despite popular belief, the absence of a strong link between mental illness and violence has been well studied and established. In summary, in a small subset of patients, mental illness provides a minor increase in the risk of committing violence.¹

In part as a result of this research, police departments across the country have established programs and protocols to divert patients with mental illness out of the legal system and into mental hospitals. Instead of accepting the common refrain that mental illness is the explanation and best predictor of all atrocious behaviors, police departments have correctly referred patients with mental illness to mental hospitals. We commend those initiatives and encourage their adoption in all locales. Yet, to safeguard such programs, we would like to warn of a potential pitfall and offer possible remedies.

Having worked in both correctional and clinical settings, we are saddened by the similar nature of the work with respect to the management of mental illness. It should defy logic to assume the need for mental health care in our jails is in any way comparable to the one in mental hospitals. However, we have grown accustomed to seeing large numbers of our most vulnerable patients with severe mental illness accumulating in our jails and correctional facilities, which often are the largest employers of mental health clinicians. The reasons correctional institutions have become so reliant on psychiatric clinicians are vast and complex. Incarceration is tremendously destabilizing and can lead to the onset or relapse of mental illness – even in the most resilient patients. In addition, mental illness is undertreated in our communities yet inescapable in the confined settings of our jails. Furthermore, our mass incarceration problems have resulted in the most disenfranchised populations, including our patients with mental illness, becoming the targets of policies criminalizing poverty.²

To prevent furthering the process by which our correctional facilities have become the new asylums,³ law enforcement agencies have enacted a vast array of initiatives. Some include the placement of mental health staff within emergency response teams. Some include training police officers in how to talk to patients with mental illness as well as how to deescalate mental health crises. Most of the initiatives have one common goal: diverting patients with mental illness who are better treated in mental hospitals from going to jail. However, herein lies the problem: If mental illness is an explanation for only a small subset of criminal behavior, why is there a large need to divert patients with mental illness from jails to mental hospitals?

Over the past few years, psychiatrists in emergency departments have noted a concerning trend: an increase in referrals to mental hospitals by law enforcement for what appears to be a crime with only a vague or obscure link to mental illness. Most psychiatrists who regularly work in emergency departments will witness many examples. Some might be fairly benign: “They were going to arrest me for trespassing; I was yelling at a coffee shop. But when I told them that I had run out of meds, they brought me here instead.”

However, some stories are more chilling, including the case of an older male who had made threats while shooting his gun in the air and was brought to the emergency department because, as the police officer told us, “I think that he is just depressed; you guys can keep him safe till he is better.”

We applaud society’s desire to reduce the criminalization of mental illness. We think that psychiatry should be deeply involved in the attempts to resolve this problem. Furthermore, we are cognizant that the number of patients with mental illness unnecessarily imprisoned as a result of prosecutorial zealousness is a larger problem than criminals inappropriately brought to mental hospitals. However, we also are aware of the limitation of psychiatric hospitals in solving nonpsychiatric problems.

If mental illness (for the most part) does not cause violence, then when patients with or without mental illness commit a violent act, the response (for the most part) should not be a psychiatric one. Recent studies have demonstrated the need to examine criminogenic needs before psychiatric ones when attempting to reduce recidivism in all offenders, including those with mental illnesses.⁴ The emphasis on addressing psychiatric needs over criminogenic ones is misguided and not based on evidence. Yet, we appreciate the complexity of those questions and of individual cases.

Substance use disorders are emblematic of this problem. Psychiatry has now communicated the position that substance use disorders are mental illness and not a moral failing. However, are the crimes committed by individuals with substance use disorders, whether in a state of intoxication or driven by the cycles of addiction, the blameless result of mental illness? The legal system struggles with this question, trying to determine when addiction-related crimes should be referred to a diversion program or treated as a straightforward criminal prosecution. Those who favor diversion for addiction can point out that many criminal acts are associated with mitigating factors that are no less valid than is addiction.

However, those mitigating factors, such as poverty, childhood deprivation, or a violence-infused sociological milieu, cannot be found in the Diagnostic and Statistical Manual of Mental Disorders. As such, if those factors alone were considered, no diversion would be offered by the courts. There also can be unforeseen consequences to this bias for diversion or criminal prosecution. Violent outbursts are a recognized part of PTSD in veterans. Psychiatrists who work at Veterans Affairs can be faced with the diagnosis of PTSD being used as an excuse for violent behavior, which may, at some level be valid, but which can be dangerous in that labeling a patient with that diagnosis might lower the barriers to violent behavior by providing a ready-made explanation already internalized by the patient through unspoken, sociocultural norms.

With the awareness of the complex nature of the intersectionality of mental illness and criminality, we recommend improvements to current diversion programs. As diversion programs rightfully continue to expand across the country, we likely will see an increase in the number of referrals by police officers to our emergency departments. Some of the referrals will be considered “inappropriate” after thorough and thoughtful clinical evaluation by emergency psychiatrists. The inappropriateness might be secondary to an absence of active symptoms, an absence of correlation between the illness and the offense, or a more urgent criminogenic need.

When faced with someone who will not benefit from diversion to a psychiatric emergency department, psychiatrists should have the tools to revert the person back into the legal system. Those tools could come in many forms – law enforcement liaison, prosecution liaison, or simply the presence of officers who are mandated to wait for the approval of the clinician prior to dismissing legal charges. Whatever the solution might be for any particular locale, policy makers should not wait for adverse events to realize the potential pitfalls of the important work being done in developing our country’s diversion programs.

References

1. Swanson JW et al. Mental illness and reduction of gun violence and suicide: Bringing epidemiologic research to policy. Ann Epidemiol. 2015 May;25(5):366-76.

2. Ehrenreich B. “How America criminalized poverty.” The Guardian. 2011 Aug 10.

3. Roth A. “Prisons are the new asylums.” The Atlantic. 2018 April.

4. Latessa EJ et al. “What works (and doesn’t) in reducing recidivism.” New York: Routledge, 2015.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.

Despite popular belief, the absence of a strong link between mental illness and violence has been well studied and established. In summary, in a small subset of patients, mental illness provides a minor increase in the risk of committing violence.¹

In part as a result of this research, police departments across the country have established programs and protocols to divert patients with mental illness out of the legal system and into mental hospitals. Instead of accepting the common refrain that mental illness is the explanation and best predictor of all atrocious behaviors, police departments have correctly referred patients with mental illness to mental hospitals. We commend those initiatives and encourage their adoption in all locales. Yet, to safeguard such programs, we would like to warn of a potential pitfall and offer possible remedies.

Having worked in both correctional and clinical settings, we are saddened by the similar nature of the work with respect to the management of mental illness. It should defy logic to assume the need for mental health care in our jails is in any way comparable to the one in mental hospitals. However, we have grown accustomed to seeing large numbers of our most vulnerable patients with severe mental illness accumulating in our jails and correctional facilities, which often are the largest employers of mental health clinicians. The reasons correctional institutions have become so reliant on psychiatric clinicians are vast and complex. Incarceration is tremendously destabilizing and can lead to the onset or relapse of mental illness – even in the most resilient patients. In addition, mental illness is undertreated in our communities yet inescapable in the confined settings of our jails. Furthermore, our mass incarceration problems have resulted in the most disenfranchised populations, including our patients with mental illness, becoming the targets of policies criminalizing poverty.²

To prevent furthering the process by which our correctional facilities have become the new asylums,³ law enforcement agencies have enacted a vast array of initiatives. Some include the placement of mental health staff within emergency response teams. Some include training police officers in how to talk to patients with mental illness as well as how to deescalate mental health crises. Most of the initiatives have one common goal: diverting patients with mental illness who are better treated in mental hospitals from going to jail. However, herein lies the problem: If mental illness is an explanation for only a small subset of criminal behavior, why is there a large need to divert patients with mental illness from jails to mental hospitals?

Over the past few years, psychiatrists in emergency departments have noted a concerning trend: an increase in referrals to mental hospitals by law enforcement for what appears to be a crime with only a vague or obscure link to mental illness. Most psychiatrists who regularly work in emergency departments will witness many examples. Some might be fairly benign: “They were going to arrest me for trespassing; I was yelling at a coffee shop. But when I told them that I had run out of meds, they brought me here instead.”

However, some stories are more chilling, including the case of an older male who had made threats while shooting his gun in the air and was brought to the emergency department because, as the police officer told us, “I think that he is just depressed; you guys can keep him safe till he is better.”

We applaud society’s desire to reduce the criminalization of mental illness. We think that psychiatry should be deeply involved in the attempts to resolve this problem. Furthermore, we are cognizant that the number of patients with mental illness unnecessarily imprisoned as a result of prosecutorial zealousness is a larger problem than criminals inappropriately brought to mental hospitals. However, we also are aware of the limitation of psychiatric hospitals in solving nonpsychiatric problems.

If mental illness (for the most part) does not cause violence, then when patients with or without mental illness commit a violent act, the response (for the most part) should not be a psychiatric one. Recent studies have demonstrated the need to examine criminogenic needs before psychiatric ones when attempting to reduce recidivism in all offenders, including those with mental illnesses.⁴ The emphasis on addressing psychiatric needs over criminogenic ones is misguided and not based on evidence. Yet, we appreciate the complexity of those questions and of individual cases.

Substance use disorders are emblematic of this problem. Psychiatry has now communicated the position that substance use disorders are mental illness and not a moral failing. However, are the crimes committed by individuals with substance use disorders, whether in a state of intoxication or driven by the cycles of addiction, the blameless result of mental illness? The legal system struggles with this question, trying to determine when addiction-related crimes should be referred to a diversion program or treated as a straightforward criminal prosecution. Those who favor diversion for addiction can point out that many criminal acts are associated with mitigating factors that are no less valid than is addiction.

However, those mitigating factors, such as poverty, childhood deprivation, or a violence-infused sociological milieu, cannot be found in the Diagnostic and Statistical Manual of Mental Disorders. As such, if those factors alone were considered, no diversion would be offered by the courts. There also can be unforeseen consequences to this bias for diversion or criminal prosecution. Violent outbursts are a recognized part of PTSD in veterans. Psychiatrists who work at Veterans Affairs can be faced with the diagnosis of PTSD being used as an excuse for violent behavior, which may, at some level be valid, but which can be dangerous in that labeling a patient with that diagnosis might lower the barriers to violent behavior by providing a ready-made explanation already internalized by the patient through unspoken, sociocultural norms.

With the awareness of the complex nature of the intersectionality of mental illness and criminality, we recommend improvements to current diversion programs. As diversion programs rightfully continue to expand across the country, we likely will see an increase in the number of referrals by police officers to our emergency departments. Some of the referrals will be considered “inappropriate” after thorough and thoughtful clinical evaluation by emergency psychiatrists. The inappropriateness might be secondary to an absence of active symptoms, an absence of correlation between the illness and the offense, or a more urgent criminogenic need.

When faced with someone who will not benefit from diversion to a psychiatric emergency department, psychiatrists should have the tools to revert the person back into the legal system. Those tools could come in many forms – law enforcement liaison, prosecution liaison, or simply the presence of officers who are mandated to wait for the approval of the clinician prior to dismissing legal charges. Whatever the solution might be for any particular locale, policy makers should not wait for adverse events to realize the potential pitfalls of the important work being done in developing our country’s diversion programs.

References

1. Swanson JW et al. Mental illness and reduction of gun violence and suicide: Bringing epidemiologic research to policy. Ann Epidemiol. 2015 May;25(5):366-76.

2. Ehrenreich B. “How America criminalized poverty.” The Guardian. 2011 Aug 10.

3. Roth A. “Prisons are the new asylums.” The Atlantic. 2018 April.

4. Latessa EJ et al. “What works (and doesn’t) in reducing recidivism.” New York: Routledge, 2015.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.

Despite popular belief, the absence of a strong link between mental illness and violence has been well studied and established. In summary, in a small subset of patients, mental illness provides a minor increase in the risk of committing violence.¹

In part as a result of this research, police departments across the country have established programs and protocols to divert patients with mental illness out of the legal system and into mental hospitals. Instead of accepting the common refrain that mental illness is the explanation and best predictor of all atrocious behaviors, police departments have correctly referred patients with mental illness to mental hospitals. We commend those initiatives and encourage their adoption in all locales. Yet, to safeguard such programs, we would like to warn of a potential pitfall and offer possible remedies.

Having worked in both correctional and clinical settings, we are saddened by the similar nature of the work with respect to the management of mental illness. It should defy logic to assume the need for mental health care in our jails is in any way comparable to the one in mental hospitals. However, we have grown accustomed to seeing large numbers of our most vulnerable patients with severe mental illness accumulating in our jails and correctional facilities, which often are the largest employers of mental health clinicians. The reasons correctional institutions have become so reliant on psychiatric clinicians are vast and complex. Incarceration is tremendously destabilizing and can lead to the onset or relapse of mental illness – even in the most resilient patients. In addition, mental illness is undertreated in our communities yet inescapable in the confined settings of our jails. Furthermore, our mass incarceration problems have resulted in the most disenfranchised populations, including our patients with mental illness, becoming the targets of policies criminalizing poverty.²

To prevent furthering the process by which our correctional facilities have become the new asylums,³ law enforcement agencies have enacted a vast array of initiatives. Some include the placement of mental health staff within emergency response teams. Some include training police officers in how to talk to patients with mental illness as well as how to deescalate mental health crises. Most of the initiatives have one common goal: diverting patients with mental illness who are better treated in mental hospitals from going to jail. However, herein lies the problem: If mental illness is an explanation for only a small subset of criminal behavior, why is there a large need to divert patients with mental illness from jails to mental hospitals?

Over the past few years, psychiatrists in emergency departments have noted a concerning trend: an increase in referrals to mental hospitals by law enforcement for what appears to be a crime with only a vague or obscure link to mental illness. Most psychiatrists who regularly work in emergency departments will witness many examples. Some might be fairly benign: “They were going to arrest me for trespassing; I was yelling at a coffee shop. But when I told them that I had run out of meds, they brought me here instead.”

However, some stories are more chilling, including the case of an older male who had made threats while shooting his gun in the air and was brought to the emergency department because, as the police officer told us, “I think that he is just depressed; you guys can keep him safe till he is better.”

We applaud society’s desire to reduce the criminalization of mental illness. We think that psychiatry should be deeply involved in the attempts to resolve this problem. Furthermore, we are cognizant that the number of patients with mental illness unnecessarily imprisoned as a result of prosecutorial zealousness is a larger problem than criminals inappropriately brought to mental hospitals. However, we also are aware of the limitation of psychiatric hospitals in solving nonpsychiatric problems.

If mental illness (for the most part) does not cause violence, then when patients with or without mental illness commit a violent act, the response (for the most part) should not be a psychiatric one. Recent studies have demonstrated the need to examine criminogenic needs before psychiatric ones when attempting to reduce recidivism in all offenders, including those with mental illnesses.⁴ The emphasis on addressing psychiatric needs over criminogenic ones is misguided and not based on evidence. Yet, we appreciate the complexity of those questions and of individual cases.

Substance use disorders are emblematic of this problem. Psychiatry has now communicated the position that substance use disorders are mental illness and not a moral failing. However, are the crimes committed by individuals with substance use disorders, whether in a state of intoxication or driven by the cycles of addiction, the blameless result of mental illness? The legal system struggles with this question, trying to determine when addiction-related crimes should be referred to a diversion program or treated as a straightforward criminal prosecution. Those who favor diversion for addiction can point out that many criminal acts are associated with mitigating factors that are no less valid than is addiction.

However, those mitigating factors, such as poverty, childhood deprivation, or a violence-infused sociological milieu, cannot be found in the Diagnostic and Statistical Manual of Mental Disorders. As such, if those factors alone were considered, no diversion would be offered by the courts. There also can be unforeseen consequences to this bias for diversion or criminal prosecution. Violent outbursts are a recognized part of PTSD in veterans. Psychiatrists who work at Veterans Affairs can be faced with the diagnosis of PTSD being used as an excuse for violent behavior, which may, at some level be valid, but which can be dangerous in that labeling a patient with that diagnosis might lower the barriers to violent behavior by providing a ready-made explanation already internalized by the patient through unspoken, sociocultural norms.

With the awareness of the complex nature of the intersectionality of mental illness and criminality, we recommend improvements to current diversion programs. As diversion programs rightfully continue to expand across the country, we likely will see an increase in the number of referrals by police officers to our emergency departments. Some of the referrals will be considered “inappropriate” after thorough and thoughtful clinical evaluation by emergency psychiatrists. The inappropriateness might be secondary to an absence of active symptoms, an absence of correlation between the illness and the offense, or a more urgent criminogenic need.

When faced with someone who will not benefit from diversion to a psychiatric emergency department, psychiatrists should have the tools to revert the person back into the legal system. Those tools could come in many forms – law enforcement liaison, prosecution liaison, or simply the presence of officers who are mandated to wait for the approval of the clinician prior to dismissing legal charges. Whatever the solution might be for any particular locale, policy makers should not wait for adverse events to realize the potential pitfalls of the important work being done in developing our country’s diversion programs.

References

1. Swanson JW et al. Mental illness and reduction of gun violence and suicide: Bringing epidemiologic research to policy. Ann Epidemiol. 2015 May;25(5):366-76.

2. Ehrenreich B. “How America criminalized poverty.” The Guardian. 2011 Aug 10.

3. Roth A. “Prisons are the new asylums.” The Atlantic. 2018 April.

4. Latessa EJ et al. “What works (and doesn’t) in reducing recidivism.” New York: Routledge, 2015.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.

Stop the selfies

If you’re a selfie aficionado, this is crucial information. People hate your selfies, and people hate you.

Okay, maybe that’s being a little aggressive, but a new study from Washington State University has shown that, if you’re a chronic selfie poster, people (aka your loyal Instagram audience) are more likely to view you as unlikable, unsuccessful, insecure, and closed off to new experiences.

The study was born from the idea that chronic selfie takers are more narcissistic than the rest of us. Chris Barry, PhD, the lead author of this study, conducted research into that hypothesis and found inconclusive results: Selfie prevalence just wasn’t indicative of personality. However, Dr. Barry realized there may be a stronger link between the amount of selfies posted and how people (whom the selfies are forced upon) perceive the selfie taker. [Editor’s note: I am more tired of reading the word “selfie” than of seeing them at this point.]

Study participants were asked to rate the Instagram profiles of 30 undergrad students on attributes such as low self-esteem, self-absorption, and success. The profiles with more posed photos were viewed as being more adventurous, more outgoing, and having high self-esteem, while the reverse was true for profiles with lots of selfies. And for the men trying online dating: Flexing-in-the-mirror selfies were viewed extra negatively.

So what have we learned from this all-important selfie study? If you want to step up your online profile, start by deleting a few of those selfies. Send them to Grandma instead, who will really appreciate your pretty face.
 

Emoji emotion

You’re setting up your online dating profile. You’ve removed all the selfies and have only the most flattering posed photos of yourself: with your dog, climbing a mountain, at the beach, all the greatest hits. You’ve been messaging the ladies nonstop, impressing them with your witty wordplay and impeccable spelling. But so far, not much is happening. What gives? According to a study from the Kinsey Institute, you’ve got to use more emojis.

Surveying more than 5,000 adults, researchers found that frequent emoji use predicted more first dates and more frequent sexual activity. The findings suggest that people who use emojis often might be better at forming connections with other people than those who eschew those ubiquitous smileys.

Is an emoji worth a thousand words? For some, apparently. The authors noted that emojis can be used in addition to words to strategically infuse digital communication with expression and emotion that typed words often lack. For many, a smiley emoji carries more emotional weight than writing that you’re happy. If you’re looking to spice up your love life, say it with emojis instead. And if you’re not well-versed in emoji speak, make sure to look up the meaning of the eggplant emoji before you use it.
 

The nomination would have been enough, really

We here at LOTME love a good survey ... Okay, most of us here at LOTME love a good survey ... All right, it looks like three out of four LOTME staffers surveyed are quite fond of a good survey.

Here, now, finally, is some news about a survey. The good folks at Crestline – whose custom-imprinted promotional products “bring your logo to life!” – asked 1,630 U.S. residents about “America’s Most Memorable Mascots.” The respondents were asked to identify and rate 82 characters representing the best of American marketing, including Colonel Sanders, Little Debbie, Chuck E. Cheese, and the Aflac duck.

In a sweep of epic proportions, the top ranking in each of five measures – least likable, least persuasive, least trustworthy, most annoying, and most creepy – went to the same character: Mr. Mucus, the face of the Mucinex brand.

Lucas Franki/MDedge News

Not so sexy after all

Another day, another organism being marketed as an aphrodisiac thanks to some dubious science, according to a report from the New Zealand Newsroom. To be fair, though, advertising a product called sexy pavement lichen as a natural male enhancement isn’t the worst-sounding idea in the world.

carstenbrandt/iStock/Getty Images Plus

The sexy lichen in question, Xanthoparmelia scabrosa, most commonly found in Australia and New Zealand, isn’t that much more attractive than any other lichen. It’s more of a nuisance than anything else, as it loves to grow in pavement and makes roads covered in the stuff dangerously slick when it rains.

As for any benefit as an aphrodisiac, the plant does contain a PDE5 inhibitor, which can inhibit an enzyme causing impotence but may also be toxic on its own. Plus you’ll be getting a dose of such heavy metals as copper, lead, cadmium, mercury, and basically anything else you’d find in asphalt.

The “legitimate” business people involved claim to grind up the actual lichen, and their product is then marketed as an ancient Chinese therapy for erectile dysfunction. A thriving market has been built around sexy pavement lichen, with thousands of tons available on websites such as Alibaba at the premium price of $100 per kg.

In reality, people are buying a combination of Viagra and grass clippings, as harvesting that much lichen would be both unfeasible and unsustainable, according to the Newsroom report. Sadly, it seems that “legitimate” business people have once again let us all down. But hey, at least they’re not selling poisonous lichen.

Stop the selfies

If you’re a selfie aficionado, this is crucial information. People hate your selfies, and people hate you.

Okay, maybe that’s being a little aggressive, but a new study from Washington State University has shown that, if you’re a chronic selfie poster, people (aka your loyal Instagram audience) are more likely to view you as unlikable, unsuccessful, insecure, and closed off to new experiences.

The study was born from the idea that chronic selfie takers are more narcissistic than the rest of us. Chris Barry, PhD, the lead author of this study, conducted research into that hypothesis and found inconclusive results: Selfie prevalence just wasn’t indicative of personality. However, Dr. Barry realized there may be a stronger link between the amount of selfies posted and how people (whom the selfies are forced upon) perceive the selfie taker. [Editor’s note: I am more tired of reading the word “selfie” than of seeing them at this point.]

Study participants were asked to rate the Instagram profiles of 30 undergrad students on attributes such as low self-esteem, self-absorption, and success. The profiles with more posed photos were viewed as being more adventurous, more outgoing, and having high self-esteem, while the reverse was true for profiles with lots of selfies. And for the men trying online dating: Flexing-in-the-mirror selfies were viewed extra negatively.

So what have we learned from this all-important selfie study? If you want to step up your online profile, start by deleting a few of those selfies. Send them to Grandma instead, who will really appreciate your pretty face.
 

Emoji emotion

You’re setting up your online dating profile. You’ve removed all the selfies and have only the most flattering posed photos of yourself: with your dog, climbing a mountain, at the beach, all the greatest hits. You’ve been messaging the ladies nonstop, impressing them with your witty wordplay and impeccable spelling. But so far, not much is happening. What gives? According to a study from the Kinsey Institute, you’ve got to use more emojis.

Surveying more than 5,000 adults, researchers found that frequent emoji use predicted more first dates and more frequent sexual activity. The findings suggest that people who use emojis often might be better at forming connections with other people than those who eschew those ubiquitous smileys.

Is an emoji worth a thousand words? For some, apparently. The authors noted that emojis can be used in addition to words to strategically infuse digital communication with expression and emotion that typed words often lack. For many, a smiley emoji carries more emotional weight than writing that you’re happy. If you’re looking to spice up your love life, say it with emojis instead. And if you’re not well-versed in emoji speak, make sure to look up the meaning of the eggplant emoji before you use it.
 

The nomination would have been enough, really

We here at LOTME love a good survey ... Okay, most of us here at LOTME love a good survey ... All right, it looks like three out of four LOTME staffers surveyed are quite fond of a good survey.

Here, now, finally, is some news about a survey. The good folks at Crestline – whose custom-imprinted promotional products “bring your logo to life!” – asked 1,630 U.S. residents about “America’s Most Memorable Mascots.” The respondents were asked to identify and rate 82 characters representing the best of American marketing, including Colonel Sanders, Little Debbie, Chuck E. Cheese, and the Aflac duck.

In a sweep of epic proportions, the top ranking in each of five measures – least likable, least persuasive, least trustworthy, most annoying, and most creepy – went to the same character: Mr. Mucus, the face of the Mucinex brand.

Lucas Franki/MDedge News

Not so sexy after all

Another day, another organism being marketed as an aphrodisiac thanks to some dubious science, according to a report from the New Zealand Newsroom. To be fair, though, advertising a product called sexy pavement lichen as a natural male enhancement isn’t the worst-sounding idea in the world.

carstenbrandt/iStock/Getty Images Plus

The sexy lichen in question, Xanthoparmelia scabrosa, most commonly found in Australia and New Zealand, isn’t that much more attractive than any other lichen. It’s more of a nuisance than anything else, as it loves to grow in pavement and makes roads covered in the stuff dangerously slick when it rains.

As for any benefit as an aphrodisiac, the plant does contain a PDE5 inhibitor, which can inhibit an enzyme causing impotence but may also be toxic on its own. Plus you’ll be getting a dose of such heavy metals as copper, lead, cadmium, mercury, and basically anything else you’d find in asphalt.

The “legitimate” business people involved claim to grind up the actual lichen, and their product is then marketed as an ancient Chinese therapy for erectile dysfunction. A thriving market has been built around sexy pavement lichen, with thousands of tons available on websites such as Alibaba at the premium price of $100 per kg.

In reality, people are buying a combination of Viagra and grass clippings, as harvesting that much lichen would be both unfeasible and unsustainable, according to the Newsroom report. Sadly, it seems that “legitimate” business people have once again let us all down. But hey, at least they’re not selling poisonous lichen.

Stop the selfies

If you’re a selfie aficionado, this is crucial information. People hate your selfies, and people hate you.

Okay, maybe that’s being a little aggressive, but a new study from Washington State University has shown that, if you’re a chronic selfie poster, people (aka your loyal Instagram audience) are more likely to view you as unlikable, unsuccessful, insecure, and closed off to new experiences.

The study was born from the idea that chronic selfie takers are more narcissistic than the rest of us. Chris Barry, PhD, the lead author of this study, conducted research into that hypothesis and found inconclusive results: Selfie prevalence just wasn’t indicative of personality. However, Dr. Barry realized there may be a stronger link between the amount of selfies posted and how people (whom the selfies are forced upon) perceive the selfie taker. [Editor’s note: I am more tired of reading the word “selfie” than of seeing them at this point.]

Study participants were asked to rate the Instagram profiles of 30 undergrad students on attributes such as low self-esteem, self-absorption, and success. The profiles with more posed photos were viewed as being more adventurous, more outgoing, and having high self-esteem, while the reverse was true for profiles with lots of selfies. And for the men trying online dating: Flexing-in-the-mirror selfies were viewed extra negatively.

So what have we learned from this all-important selfie study? If you want to step up your online profile, start by deleting a few of those selfies. Send them to Grandma instead, who will really appreciate your pretty face.
 

Emoji emotion

You’re setting up your online dating profile. You’ve removed all the selfies and have only the most flattering posed photos of yourself: with your dog, climbing a mountain, at the beach, all the greatest hits. You’ve been messaging the ladies nonstop, impressing them with your witty wordplay and impeccable spelling. But so far, not much is happening. What gives? According to a study from the Kinsey Institute, you’ve got to use more emojis.

Surveying more than 5,000 adults, researchers found that frequent emoji use predicted more first dates and more frequent sexual activity. The findings suggest that people who use emojis often might be better at forming connections with other people than those who eschew those ubiquitous smileys.

Is an emoji worth a thousand words? For some, apparently. The authors noted that emojis can be used in addition to words to strategically infuse digital communication with expression and emotion that typed words often lack. For many, a smiley emoji carries more emotional weight than writing that you’re happy. If you’re looking to spice up your love life, say it with emojis instead. And if you’re not well-versed in emoji speak, make sure to look up the meaning of the eggplant emoji before you use it.
 

The nomination would have been enough, really

We here at LOTME love a good survey ... Okay, most of us here at LOTME love a good survey ... All right, it looks like three out of four LOTME staffers surveyed are quite fond of a good survey.

Here, now, finally, is some news about a survey. The good folks at Crestline – whose custom-imprinted promotional products “bring your logo to life!” – asked 1,630 U.S. residents about “America’s Most Memorable Mascots.” The respondents were asked to identify and rate 82 characters representing the best of American marketing, including Colonel Sanders, Little Debbie, Chuck E. Cheese, and the Aflac duck.

In a sweep of epic proportions, the top ranking in each of five measures – least likable, least persuasive, least trustworthy, most annoying, and most creepy – went to the same character: Mr. Mucus, the face of the Mucinex brand.

Lucas Franki/MDedge News

Not so sexy after all

Another day, another organism being marketed as an aphrodisiac thanks to some dubious science, according to a report from the New Zealand Newsroom. To be fair, though, advertising a product called sexy pavement lichen as a natural male enhancement isn’t the worst-sounding idea in the world.

carstenbrandt/iStock/Getty Images Plus

The sexy lichen in question, Xanthoparmelia scabrosa, most commonly found in Australia and New Zealand, isn’t that much more attractive than any other lichen. It’s more of a nuisance than anything else, as it loves to grow in pavement and makes roads covered in the stuff dangerously slick when it rains.

As for any benefit as an aphrodisiac, the plant does contain a PDE5 inhibitor, which can inhibit an enzyme causing impotence but may also be toxic on its own. Plus you’ll be getting a dose of such heavy metals as copper, lead, cadmium, mercury, and basically anything else you’d find in asphalt.

The “legitimate” business people involved claim to grind up the actual lichen, and their product is then marketed as an ancient Chinese therapy for erectile dysfunction. A thriving market has been built around sexy pavement lichen, with thousands of tons available on websites such as Alibaba at the premium price of $100 per kg.

In reality, people are buying a combination of Viagra and grass clippings, as harvesting that much lichen would be both unfeasible and unsustainable, according to the Newsroom report. Sadly, it seems that “legitimate” business people have once again let us all down. But hey, at least they’re not selling poisonous lichen.

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.