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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
New topicals for excessive sweating are in sight
Safe and effective of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.
Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.
Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.
“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.
Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
Sofpironium bromide gel
Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.
Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.
An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.
The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.
The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.
The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.
A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.
Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.
“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”
Glycopyrronium bromide cream
Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.
The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.
The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).
Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.
Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.
Safe and effective of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.
Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.
Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.
“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.
Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
Sofpironium bromide gel
Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.
Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.
An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.
The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.
The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.
The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.
A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.
Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.
“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”
Glycopyrronium bromide cream
Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.
The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.
The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).
Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.
Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.
Safe and effective of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.
Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.
Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.
“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.
Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
Sofpironium bromide gel
Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.
Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.
An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.
The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.
The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.
The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.
A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.
Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.
“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”
Glycopyrronium bromide cream
Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.
The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.
The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).
Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.
Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.
FROM AAD 20
For suspected hair disorders, consider trichoscopy before biopsy
In the clinical experience of Bianca Maria Piraccini, MD,
Dermoscopic imaging, also known as trichoscopy, “avoids invasive procedures and provides immediate results,” Dr. Piraccini, of the University of Bologna’s division of dermatology in the department of experimental, diagnostic, and specialty medicine, said during the virtual annual meeting of the Society for Pediatric Dermatology. “It is helpful for diagnosing all sorts of alopecia, starting with those that appear at birth, such as aplasia cutis congenita to those that appear in adolescence, such as androgenetic alopecia.”
Dr. Piraccini noted that lanugo hair is produced at 16-20 weeks’ gestation and is shed in utero and replaced by thicker hair at 32-36 weeks. “The speed of transition from vellus to intermediate and terminal hair varies from child to child,” she said. “The scalp at birth presents with thin, intermediate, or thick hair.”
In a dermoscopic evaluation of hair in 45 neonates during their first 30 days of life, Dr. Piraccini and colleagues found that 70% had low density hair while the remaining 30% had high density hair (Br J Dermatol 2013; 169:896-900). Two neonates presented a frontal-temporal pattern of hair loss. Trichoscopy revealed that nine neonates, all in the poor hair density group, had a particular hair shaft dermoscopic feature, characterized by the presence of widespread thin hair.
In some children, she continued, hair in the occipital area does not enter the telogen phase until after birth. These hairs remain on the scalp for 8-12 weeks and then fall out, resulting in neonatal occipital alopecia, which is the most common form of transient neonatal hair loss. Neonatal occipital alopecia is characterized by a band-like shape or oval alopecic patch with a sharp lower margin, but it often goes unnoticed by parents.
“It occurs with higher prevalence in infants born to mothers younger than age 34, in those with a non-cesarean birth, and in those with a gestational age greater than 37 weeks,” Dr. Piraccini said. “There are different degrees of severity. On trichoscopy, the condition appears as thin regrowing hair. The outcome is totally benign, with normal hair growth within the first year of life.”
Any aspect of alopecia in the occipital area in young children may be a sign of hair shaft disorders, which are characterized by increased hair fragility. “Trichoscopy is diagnostic,” she said. “When applied to the hair you see monilethrix, a rare inherited disorder characterized by sparse, brittle hair that often breaks before reaching a few inches in length. As the child grows, the hair gradually acquires the characteristics it will have in adulthood. “It may remain thin and with a short anagen phase for several years, but acute shedding is rare,” she said.
When an older child presents with increased hair shedding, the first exam to perform is the pull test. If it results in painless traction of several anagen hair without sheaths and with ragged cuticles, think about loose anagen hair syndrome. This condition affects females more than males, usually occurs between the ages of 2 and 5, and is characterized by a defective anchoring of the hair shaft to the hair follicle. The three clinical types of loose anagen hair syndrome are short, rough sparse hair; increased shedding; and areas of alopecia. The syndrome “tends to be inherited but spontaneously improves with aging,” Dr. Piraccini said.
Alopecia areata, another common pediatric hair disorder, occurs in 20% of patients younger than 16 years of age and 9% of those with Down syndrome, and is associated with a family history of the condition. Young age at onset is a negative prognostic factor. “On trichoscopy, common features of alopecia areata are yellow dots, black dots, exclamation mark hairs, and broken hair,” she said. “Trichoscopy can also help you distinguish acute from chronic alopecia areata. The risk of relapse is common, and psychological support is mandatory, because it is very stressful for children.”
Another form of patchy alopecia, trichotillomania, occurs mainly in school-aged children and appears as irregular patches of alopecia with hairs broken at different lengths. “The pull test is negative because all telogen hairs have been pulled out by the patient,” Dr. Piraccini said. “Parents often do not accept the diagnosis as they do not see the child touching his or her hair. It has a good prognosis.”
Trichoscopic signs of trichotillomania include black dots, hair broken at different length, flame hair, clots of hair, and tulip hair. Treatment typically consists of psychological counseling and N-acetylcysteine 600-2,400 g/day.
Dr. Piraccini reported having no relevant financial disclosures.
In the clinical experience of Bianca Maria Piraccini, MD,
Dermoscopic imaging, also known as trichoscopy, “avoids invasive procedures and provides immediate results,” Dr. Piraccini, of the University of Bologna’s division of dermatology in the department of experimental, diagnostic, and specialty medicine, said during the virtual annual meeting of the Society for Pediatric Dermatology. “It is helpful for diagnosing all sorts of alopecia, starting with those that appear at birth, such as aplasia cutis congenita to those that appear in adolescence, such as androgenetic alopecia.”
Dr. Piraccini noted that lanugo hair is produced at 16-20 weeks’ gestation and is shed in utero and replaced by thicker hair at 32-36 weeks. “The speed of transition from vellus to intermediate and terminal hair varies from child to child,” she said. “The scalp at birth presents with thin, intermediate, or thick hair.”
In a dermoscopic evaluation of hair in 45 neonates during their first 30 days of life, Dr. Piraccini and colleagues found that 70% had low density hair while the remaining 30% had high density hair (Br J Dermatol 2013; 169:896-900). Two neonates presented a frontal-temporal pattern of hair loss. Trichoscopy revealed that nine neonates, all in the poor hair density group, had a particular hair shaft dermoscopic feature, characterized by the presence of widespread thin hair.
In some children, she continued, hair in the occipital area does not enter the telogen phase until after birth. These hairs remain on the scalp for 8-12 weeks and then fall out, resulting in neonatal occipital alopecia, which is the most common form of transient neonatal hair loss. Neonatal occipital alopecia is characterized by a band-like shape or oval alopecic patch with a sharp lower margin, but it often goes unnoticed by parents.
“It occurs with higher prevalence in infants born to mothers younger than age 34, in those with a non-cesarean birth, and in those with a gestational age greater than 37 weeks,” Dr. Piraccini said. “There are different degrees of severity. On trichoscopy, the condition appears as thin regrowing hair. The outcome is totally benign, with normal hair growth within the first year of life.”
Any aspect of alopecia in the occipital area in young children may be a sign of hair shaft disorders, which are characterized by increased hair fragility. “Trichoscopy is diagnostic,” she said. “When applied to the hair you see monilethrix, a rare inherited disorder characterized by sparse, brittle hair that often breaks before reaching a few inches in length. As the child grows, the hair gradually acquires the characteristics it will have in adulthood. “It may remain thin and with a short anagen phase for several years, but acute shedding is rare,” she said.
When an older child presents with increased hair shedding, the first exam to perform is the pull test. If it results in painless traction of several anagen hair without sheaths and with ragged cuticles, think about loose anagen hair syndrome. This condition affects females more than males, usually occurs between the ages of 2 and 5, and is characterized by a defective anchoring of the hair shaft to the hair follicle. The three clinical types of loose anagen hair syndrome are short, rough sparse hair; increased shedding; and areas of alopecia. The syndrome “tends to be inherited but spontaneously improves with aging,” Dr. Piraccini said.
Alopecia areata, another common pediatric hair disorder, occurs in 20% of patients younger than 16 years of age and 9% of those with Down syndrome, and is associated with a family history of the condition. Young age at onset is a negative prognostic factor. “On trichoscopy, common features of alopecia areata are yellow dots, black dots, exclamation mark hairs, and broken hair,” she said. “Trichoscopy can also help you distinguish acute from chronic alopecia areata. The risk of relapse is common, and psychological support is mandatory, because it is very stressful for children.”
Another form of patchy alopecia, trichotillomania, occurs mainly in school-aged children and appears as irregular patches of alopecia with hairs broken at different lengths. “The pull test is negative because all telogen hairs have been pulled out by the patient,” Dr. Piraccini said. “Parents often do not accept the diagnosis as they do not see the child touching his or her hair. It has a good prognosis.”
Trichoscopic signs of trichotillomania include black dots, hair broken at different length, flame hair, clots of hair, and tulip hair. Treatment typically consists of psychological counseling and N-acetylcysteine 600-2,400 g/day.
Dr. Piraccini reported having no relevant financial disclosures.
In the clinical experience of Bianca Maria Piraccini, MD,
Dermoscopic imaging, also known as trichoscopy, “avoids invasive procedures and provides immediate results,” Dr. Piraccini, of the University of Bologna’s division of dermatology in the department of experimental, diagnostic, and specialty medicine, said during the virtual annual meeting of the Society for Pediatric Dermatology. “It is helpful for diagnosing all sorts of alopecia, starting with those that appear at birth, such as aplasia cutis congenita to those that appear in adolescence, such as androgenetic alopecia.”
Dr. Piraccini noted that lanugo hair is produced at 16-20 weeks’ gestation and is shed in utero and replaced by thicker hair at 32-36 weeks. “The speed of transition from vellus to intermediate and terminal hair varies from child to child,” she said. “The scalp at birth presents with thin, intermediate, or thick hair.”
In a dermoscopic evaluation of hair in 45 neonates during their first 30 days of life, Dr. Piraccini and colleagues found that 70% had low density hair while the remaining 30% had high density hair (Br J Dermatol 2013; 169:896-900). Two neonates presented a frontal-temporal pattern of hair loss. Trichoscopy revealed that nine neonates, all in the poor hair density group, had a particular hair shaft dermoscopic feature, characterized by the presence of widespread thin hair.
In some children, she continued, hair in the occipital area does not enter the telogen phase until after birth. These hairs remain on the scalp for 8-12 weeks and then fall out, resulting in neonatal occipital alopecia, which is the most common form of transient neonatal hair loss. Neonatal occipital alopecia is characterized by a band-like shape or oval alopecic patch with a sharp lower margin, but it often goes unnoticed by parents.
“It occurs with higher prevalence in infants born to mothers younger than age 34, in those with a non-cesarean birth, and in those with a gestational age greater than 37 weeks,” Dr. Piraccini said. “There are different degrees of severity. On trichoscopy, the condition appears as thin regrowing hair. The outcome is totally benign, with normal hair growth within the first year of life.”
Any aspect of alopecia in the occipital area in young children may be a sign of hair shaft disorders, which are characterized by increased hair fragility. “Trichoscopy is diagnostic,” she said. “When applied to the hair you see monilethrix, a rare inherited disorder characterized by sparse, brittle hair that often breaks before reaching a few inches in length. As the child grows, the hair gradually acquires the characteristics it will have in adulthood. “It may remain thin and with a short anagen phase for several years, but acute shedding is rare,” she said.
When an older child presents with increased hair shedding, the first exam to perform is the pull test. If it results in painless traction of several anagen hair without sheaths and with ragged cuticles, think about loose anagen hair syndrome. This condition affects females more than males, usually occurs between the ages of 2 and 5, and is characterized by a defective anchoring of the hair shaft to the hair follicle. The three clinical types of loose anagen hair syndrome are short, rough sparse hair; increased shedding; and areas of alopecia. The syndrome “tends to be inherited but spontaneously improves with aging,” Dr. Piraccini said.
Alopecia areata, another common pediatric hair disorder, occurs in 20% of patients younger than 16 years of age and 9% of those with Down syndrome, and is associated with a family history of the condition. Young age at onset is a negative prognostic factor. “On trichoscopy, common features of alopecia areata are yellow dots, black dots, exclamation mark hairs, and broken hair,” she said. “Trichoscopy can also help you distinguish acute from chronic alopecia areata. The risk of relapse is common, and psychological support is mandatory, because it is very stressful for children.”
Another form of patchy alopecia, trichotillomania, occurs mainly in school-aged children and appears as irregular patches of alopecia with hairs broken at different lengths. “The pull test is negative because all telogen hairs have been pulled out by the patient,” Dr. Piraccini said. “Parents often do not accept the diagnosis as they do not see the child touching his or her hair. It has a good prognosis.”
Trichoscopic signs of trichotillomania include black dots, hair broken at different length, flame hair, clots of hair, and tulip hair. Treatment typically consists of psychological counseling and N-acetylcysteine 600-2,400 g/day.
Dr. Piraccini reported having no relevant financial disclosures.
FROM SPD 2020
Postpartum tubal ligation safe in obese women
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
FROM OBSTETRICS & GYNECOLOGY
Biologics may delay psoriatic arthritis, study finds
(DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.
About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.
“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.
The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).
They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).
The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.
The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.
He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”
Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.
Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.
(DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.
About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.
“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.
The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).
They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).
The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.
The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.
He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”
Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.
Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.
(DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.
About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.
“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.
The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).
They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).
The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.
The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.
He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”
Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.
Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.
FROM GRAPPA 2020 VIRTUAL ANNUAL MEETING
Plasma exchange is ‘encouraging’ as a novel Alzheimer’s disease treatment
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Global study to track COVID-19’s impact on the brain
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
PANS may be more prevalent than thought
Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.
PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.
Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.
“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”
Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.
“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”
The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.
Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).
“These can be really sick kids,” Dr. Chang said. not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
Treatment for PANS
Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.
“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”
In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.
There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.
“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”
Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.
Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.
“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.
Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.
Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.
PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.
Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.
“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”
Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.
“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”
The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.
Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).
“These can be really sick kids,” Dr. Chang said. not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
Treatment for PANS
Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.
“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”
In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.
There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.
“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”
Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.
Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.
“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.
Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.
Pediatric acute-onset neuropsychiatric syndrome (PANS), a rare acute onset of psychiatric symptoms, might be more common than initially thought, according to Kiki D. Chang, MD.
PANS is characterized by the National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center as a “sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms.” These symptoms can include anxiety, depression, oppositional behavior, difficulty concentrating, abnormalities in motor and sensory skills, and other somatic symptoms. The condition develops as a result of an infection that causes an autoimmune or inflammatory response in the brain, and patients tend to respond well to treatment from antibiotics, anti-inflammatory medication, and immunomodulatory therapy.
Both PANS and a subtype condition, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS), are underrecognized, Dr. Chang said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. It is often misdiagnosed as Tourette syndrome or obsessive-compulsive disorder (OCD) because tics are present in about half of cases, he said, but more severe associated symptoms, such as psychosis, can be misdiagnosed as psychotic disorders or mood disorders. Currently, neither PANS nor PANDAS are officially recognized by the American Academy of Pediatrics or the DSM-5.
“We’re hoping that it is soon because it clearly exists,” Dr. Chang said at the meeting, presented by Global Academy for Medical Education. “If you’ve ever treated a child with PANS or PANDAS and you have seen antibiotics totally reverse OCD and tic-like behavior, if you’ve seen prednisone actually treat symptoms of mania or even psychosis and actually make those things better rather than worse, it’s really eye-opening and it makes a believer out of you.”
Anxiety is the most common psychiatric symptom in youth, and anxiety disorders are also common, said Dr. Chang. According to the National Comorbidity Survey: Adolescent Supplement, 2001-2004, 31.9% adolescents overall reported an anxiety disorder, and 8.3% said their anxiety disorder caused severe impairment. The COVID-19 pandemic has increased the level of anxiety for children and adolescents, which can lead to other disorders, such as separation anxiety disorder, panic disorder, specific phobia, social anxiety disorder, acute stress disorder, generalized anxiety disorder, OCD, or posttraumatic stress disorder. Psychiatrists should be suspicious of any sudden onset of symptoms that overlap with PANS, said Dr. Chang, who is now in private practice in Palo Alto, Calif.
“Anxiety disorders are incredibly common. Remember that you’ve got to carefully screen for other anxiety disorders, because they’re highly comorbid,” Dr. Chang said. “You’ve got to do a full workup. If there are other things going on, you’ve got to think PANS. If it’s acute onset, you’ve really got to think [PANS], and you should do that workup or refer to someone who does.”
The prevalence of PANS and PANDAS is not known, but it may be more common than psychiatrists realize, Dr. Chang said. “I’ve been doing this for about 10 years now in the PANS and PANDAS field, and it’s very clear to me that this is something that is prevalent,” he said.
Together with Jennifer Frankovich, MD, Dr. Chang founded a clinic at the Lucile Packard Children’s Hospital Stanford, and also helped to develop treatment guidelines for youth with PANS. At the clinic, patients are approximately 7.7 years old when developing the first symptoms, and are 10.7 years old when presenting for treatment. Most patients at the clinic are male (78%), and 40% are acute onset cases. Nearly all patients have symptoms of anxiety (92%), mood disorder (88%), OCD (86%), sensory/motor abnormalities (88%), irritability/aggression (82%), somatic symptoms, deterioration in school (76%), and behavioral regression (59%). More than one-third present with suicidal ideation (38%) and violence to themselves (29%), others (38%), or objects. About one-fourth have symptoms of psychosis (24%).
“These can be really sick kids,” Dr. Chang said. not able to eat because they’re afraid of things, not able to take care of their body or daily living. These were sometimes highly functional people beforehand, sometimes they weren’t, but it was still an acute change.”
Treatment for PANS
Treatment guidelines released by the PANS/PANDAS Consortium in 2017 recommend a first course of antistreptococcal treatment for new PANS cases. Psychiatrists should look for evidence of strep or other infection and use antibiotics to eradicate any underlying acute or residual infection.
“Very commonly, we’ll use things like azithromycin, or Augmentin, or amoxicillin, and you’ll see suddenly the OCD go away or at least diminish, the sleep return to normal, the mood come back down,” Dr. Chang said. “It’s pretty amazing when you see it.”
In other cases, ongoing treatment is needed for longer than the normal 5-day or 10-day course of antibiotics. “We’re not exactly sure how long: sometimes it’s 3 weeks, sometimes it’s 4 weeks, but you have to give it more than a week. Sometimes it’s the anti-inflammatory properties that are helping.” While concerns about haphazardly prescribing antibiotics are valid, “if you can cure this stuff on antibiotics, it’s low-hanging fruit,” Dr. Chang said.
There is evidence in the literature that prescribing antibiotics for PANS is beneficial. A randomized controlled trial published in 2017 showed that patients with PANS prescribed azithromycin for 4 weeks had greater reductions in severity of OCD, compared with placebo.
“We need more studies, but clearly, antibiotics do have the potential to help with certain kids. And certainly, in my practice, I see sometimes a slam-dunk response,” Dr. Chang said. “Unfortunately, sometimes you don’t see a slam-dunk response or you can’t find an infection. That’s when it might be more of an inflammation from some other reason. It could be a leftover infection, or it could be an anti-inflammatory situation.”
Immunomodulatory treatment for PANS includes use of NSAIDs, such as ibuprofen or naproxen sodium; steroids, such as prednisone or intravenous corticosteroids; intravenous immunoglobulin; or plasma exchange. Other therapies to consider are rituximab, mycophenolate mofetil, and cyclophosphamide.
Some psychiatric treatments may help patients with PANS. While there is no empirical evidence that psychotropics are effective in treating PANS, some SSRIs might help if patients are able to handle any adverse events. Psychotherapy and education of the family are also important for patients with PANS and their caregivers.
“Basically, [PANS] has as high a caregiver burden as having someone in the household with Alzheimer’s disease or cancer. It’s a huge burden, it’s very stressful, and the family needs support for this,” Dr. Chang said.
Global Academy and this news organization are owned by the same parent company. Dr. Chang reports he is a consultant for Allergan, Impel NeuroPharma, and Sunovion. He is also on the speaker’s bureau for Sunovion.
FROM CP/AACP PSYCHIATRY UPDATE
‘Long sleep’ or apnea in middle age double risk for Alzheimer’s disease
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Infection ups mortality risk in patients with dementia
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
P-tau217 differentiates Alzheimer’s disease from other neurodegenerative conditions
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020