Key clinical point: Rate of COVID-19 hospitalizations varied by treatment modalities in patients with atopic dermatitis (AD) who received immunomodulatory drugs.

Major finding: Rate of COVID-19 hospitalizations was higher among patients who received topical treatment vs dupilumab (adjusted odds ratio [aOR] 4.99; 95% CI 1.4-20.84) or combination therapy with systemic corticosteroids vs monotherapy with nonsteroidal immunosuppressants (aOR 45.75; 95% CI 4.54-616.22).

Study details: Findings are from the SECURE-AD registry including 442 patients with AD and a diagnosis of COVID-19 who received immunomodulatory treatments.

Disclosures: This study is funded by the University of Amsterdam and other sources. Some authors declared serving as employees or receiving grants, consulting fees, honoraria, or travel support from several sources.

Source: Musters AH et al. The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry. J Eur Acad Dermatol Venereol. 2022 (Sep 28). Doi: 10.1111/jdv.18613

Key clinical point: Rate of COVID-19 hospitalizations varied by treatment modalities in patients with atopic dermatitis (AD) who received immunomodulatory drugs.

Major finding: Rate of COVID-19 hospitalizations was higher among patients who received topical treatment vs dupilumab (adjusted odds ratio [aOR] 4.99; 95% CI 1.4-20.84) or combination therapy with systemic corticosteroids vs monotherapy with nonsteroidal immunosuppressants (aOR 45.75; 95% CI 4.54-616.22).

Study details: Findings are from the SECURE-AD registry including 442 patients with AD and a diagnosis of COVID-19 who received immunomodulatory treatments.

Disclosures: This study is funded by the University of Amsterdam and other sources. Some authors declared serving as employees or receiving grants, consulting fees, honoraria, or travel support from several sources.

Source: Musters AH et al. The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry. J Eur Acad Dermatol Venereol. 2022 (Sep 28). Doi: 10.1111/jdv.18613

Key clinical point: Rate of COVID-19 hospitalizations varied by treatment modalities in patients with atopic dermatitis (AD) who received immunomodulatory drugs.

Major finding: Rate of COVID-19 hospitalizations was higher among patients who received topical treatment vs dupilumab (adjusted odds ratio [aOR] 4.99; 95% CI 1.4-20.84) or combination therapy with systemic corticosteroids vs monotherapy with nonsteroidal immunosuppressants (aOR 45.75; 95% CI 4.54-616.22).

Study details: Findings are from the SECURE-AD registry including 442 patients with AD and a diagnosis of COVID-19 who received immunomodulatory treatments.

Disclosures: This study is funded by the University of Amsterdam and other sources. Some authors declared serving as employees or receiving grants, consulting fees, honoraria, or travel support from several sources.

Source: Musters AH et al. The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry. J Eur Acad Dermatol Venereol. 2022 (Sep 28). Doi: 10.1111/jdv.18613

Key clinical point: Tralokinumab, with or without topical corticosteroids (TCS), demonstrated significant efficacy in reducing disease severity and was well-tolerated in North American patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients receiving tralokinumab vs placebo achieved ≥75% improvement in the Eczema Area and Severity Index in ECZTRA 1/2 (40.1% vs 19.4%; P < .001) and ECZTRA 3 (58.1% vs 37.0%; P  =  .012) studies. Tralokinumab with or without TCS was also well-tolerated in the North American population.

Study details: Findings are from a post hoc analysis of three tralokinumab trials including patients with moderate-to-severe AD who were randomly assigned to receive tralokinumab or placebo, both with TCS as needed (ECZTRA 3; n = 160) or without TCS (ECZTRA 1 and 2; n = 559).

Disclosures: The ECZTRA trials were sponsored by LEO Pharma A/S. Three authors declared being current or former employees of LEO Pharma. The other authors reported ties with several sources, including LEO Pharma.

Source: Blauvelt A et al. Tralokinumab efficacy and safety, with or without topical corticosteroids, in North American adults with moderate-to-severe atopic dermatitis: A subanalysis of phase 3 trials ECZTRA 1, 2, and 3. Dermatol Ther (Heidelb). 2022 (Sep 24). Doi: 10.1007/s13555-022-00805-y

Key clinical point: Tralokinumab, with or without topical corticosteroids (TCS), demonstrated significant efficacy in reducing disease severity and was well-tolerated in North American patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients receiving tralokinumab vs placebo achieved ≥75% improvement in the Eczema Area and Severity Index in ECZTRA 1/2 (40.1% vs 19.4%; P < .001) and ECZTRA 3 (58.1% vs 37.0%; P  =  .012) studies. Tralokinumab with or without TCS was also well-tolerated in the North American population.

Study details: Findings are from a post hoc analysis of three tralokinumab trials including patients with moderate-to-severe AD who were randomly assigned to receive tralokinumab or placebo, both with TCS as needed (ECZTRA 3; n = 160) or without TCS (ECZTRA 1 and 2; n = 559).

Disclosures: The ECZTRA trials were sponsored by LEO Pharma A/S. Three authors declared being current or former employees of LEO Pharma. The other authors reported ties with several sources, including LEO Pharma.

Source: Blauvelt A et al. Tralokinumab efficacy and safety, with or without topical corticosteroids, in North American adults with moderate-to-severe atopic dermatitis: A subanalysis of phase 3 trials ECZTRA 1, 2, and 3. Dermatol Ther (Heidelb). 2022 (Sep 24). Doi: 10.1007/s13555-022-00805-y

Key clinical point: Tralokinumab, with or without topical corticosteroids (TCS), demonstrated significant efficacy in reducing disease severity and was well-tolerated in North American patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, a significantly higher proportion of patients receiving tralokinumab vs placebo achieved ≥75% improvement in the Eczema Area and Severity Index in ECZTRA 1/2 (40.1% vs 19.4%; P < .001) and ECZTRA 3 (58.1% vs 37.0%; P  =  .012) studies. Tralokinumab with or without TCS was also well-tolerated in the North American population.

Study details: Findings are from a post hoc analysis of three tralokinumab trials including patients with moderate-to-severe AD who were randomly assigned to receive tralokinumab or placebo, both with TCS as needed (ECZTRA 3; n = 160) or without TCS (ECZTRA 1 and 2; n = 559).

Disclosures: The ECZTRA trials were sponsored by LEO Pharma A/S. Three authors declared being current or former employees of LEO Pharma. The other authors reported ties with several sources, including LEO Pharma.

Source: Blauvelt A et al. Tralokinumab efficacy and safety, with or without topical corticosteroids, in North American adults with moderate-to-severe atopic dermatitis: A subanalysis of phase 3 trials ECZTRA 1, 2, and 3. Dermatol Ther (Heidelb). 2022 (Sep 24). Doi: 10.1007/s13555-022-00805-y

Key clinical point: Certain cutaneous biomarkers isolated from the clinically healthy skin of 2-month-old infants were able to predict the onset of atopic dermatitis (AD) in the first year of life.

Major finding: Skin thymus- and activation-regulated chemokine levels were slightly but significantly higher (0.02 vs 0.01 pg/μg, P  =  .01), phytosphingosine levels were significantly lower (238 vs 535 pmol/mg, P < .001), and sphingoid bases of chain lengths 17 (P  =  .02) and 18 (P  =  .000001) were different in children who developed vs did not develop AD.

Study details: Findings are from a prospective birth cohort study that analyzed tape strips collected at 2 months of age before AD onset in 44 children who developed AD in the first year of life and 44 matched controls who did not develop AD.

Disclosures: This study was supported by the LEO Foundation and other sources. Four authors declared serving as advisors, speakers, or consultants, or receiving research grants or support from several sources, including LEO Pharma. The other authors reported no conflicts of interest.

Source: Rinnov MR et al. Skin biomarkers predict development of atopic dermatitis in infancy. Allergy. 2022 (Sep 16). Doi: 10.1111/all.15518

Key clinical point: Certain cutaneous biomarkers isolated from the clinically healthy skin of 2-month-old infants were able to predict the onset of atopic dermatitis (AD) in the first year of life.

Major finding: Skin thymus- and activation-regulated chemokine levels were slightly but significantly higher (0.02 vs 0.01 pg/μg, P  =  .01), phytosphingosine levels were significantly lower (238 vs 535 pmol/mg, P < .001), and sphingoid bases of chain lengths 17 (P  =  .02) and 18 (P  =  .000001) were different in children who developed vs did not develop AD.

Study details: Findings are from a prospective birth cohort study that analyzed tape strips collected at 2 months of age before AD onset in 44 children who developed AD in the first year of life and 44 matched controls who did not develop AD.

Disclosures: This study was supported by the LEO Foundation and other sources. Four authors declared serving as advisors, speakers, or consultants, or receiving research grants or support from several sources, including LEO Pharma. The other authors reported no conflicts of interest.

Source: Rinnov MR et al. Skin biomarkers predict development of atopic dermatitis in infancy. Allergy. 2022 (Sep 16). Doi: 10.1111/all.15518

Key clinical point: Certain cutaneous biomarkers isolated from the clinically healthy skin of 2-month-old infants were able to predict the onset of atopic dermatitis (AD) in the first year of life.

Major finding: Skin thymus- and activation-regulated chemokine levels were slightly but significantly higher (0.02 vs 0.01 pg/μg, P  =  .01), phytosphingosine levels were significantly lower (238 vs 535 pmol/mg, P < .001), and sphingoid bases of chain lengths 17 (P  =  .02) and 18 (P  =  .000001) were different in children who developed vs did not develop AD.

Study details: Findings are from a prospective birth cohort study that analyzed tape strips collected at 2 months of age before AD onset in 44 children who developed AD in the first year of life and 44 matched controls who did not develop AD.

Disclosures: This study was supported by the LEO Foundation and other sources. Four authors declared serving as advisors, speakers, or consultants, or receiving research grants or support from several sources, including LEO Pharma. The other authors reported no conflicts of interest.

Source: Rinnov MR et al. Skin biomarkers predict development of atopic dermatitis in infancy. Allergy. 2022 (Sep 16). Doi: 10.1111/all.15518

Key clinical point: Abrocitinib demonstrated a rapid improvement in the signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, a higher proportion of patients receiving 200/100 mg abrocitinib (70.3%/58.7%) vs placebo (27.1%) achieved ≥75% improvement in the Eczema Area and Severity Index (EASI-75). The time to achieve EASI-75 was significantly lower in the 200/100 mg abrocitinib vs placebo group (29/57 days vs 114 days; 2-sided P < .0001).

Study details: Findings are from the phase 3 JADE COMPARE study including adults with moderate-to-severe AD who were randomly assigned to receive 200/100 mg oral abrocitinib once daily+placebo, dupilumab+placebo, or placebo for 16 weeks.

Disclosures: This study was funded by Pfizer, Inc. Five authors declared being current or former employees and stockholders of Pfizer. The other authors reported ties with several sources.

Source: Reich K et al. Magnitude and time course of response to abrocitinib for moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Pract. 2022 (Sep 12). Doi: 10.1016/j.jaip.2022.08.042

Key clinical point: Abrocitinib demonstrated a rapid improvement in the signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, a higher proportion of patients receiving 200/100 mg abrocitinib (70.3%/58.7%) vs placebo (27.1%) achieved ≥75% improvement in the Eczema Area and Severity Index (EASI-75). The time to achieve EASI-75 was significantly lower in the 200/100 mg abrocitinib vs placebo group (29/57 days vs 114 days; 2-sided P < .0001).

Study details: Findings are from the phase 3 JADE COMPARE study including adults with moderate-to-severe AD who were randomly assigned to receive 200/100 mg oral abrocitinib once daily+placebo, dupilumab+placebo, or placebo for 16 weeks.

Disclosures: This study was funded by Pfizer, Inc. Five authors declared being current or former employees and stockholders of Pfizer. The other authors reported ties with several sources.

Source: Reich K et al. Magnitude and time course of response to abrocitinib for moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Pract. 2022 (Sep 12). Doi: 10.1016/j.jaip.2022.08.042

Key clinical point: Abrocitinib demonstrated a rapid improvement in the signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, a higher proportion of patients receiving 200/100 mg abrocitinib (70.3%/58.7%) vs placebo (27.1%) achieved ≥75% improvement in the Eczema Area and Severity Index (EASI-75). The time to achieve EASI-75 was significantly lower in the 200/100 mg abrocitinib vs placebo group (29/57 days vs 114 days; 2-sided P < .0001).

Study details: Findings are from the phase 3 JADE COMPARE study including adults with moderate-to-severe AD who were randomly assigned to receive 200/100 mg oral abrocitinib once daily+placebo, dupilumab+placebo, or placebo for 16 weeks.

Disclosures: This study was funded by Pfizer, Inc. Five authors declared being current or former employees and stockholders of Pfizer. The other authors reported ties with several sources.

Source: Reich K et al. Magnitude and time course of response to abrocitinib for moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Pract. 2022 (Sep 12). Doi: 10.1016/j.jaip.2022.08.042

Key clinical point: Patients with atopic dermatitis (AD) who received ruxolitinib achieved an itch-free state within 2 days, which was maintained throughout the 8-week treatment period.

Major finding: A significantly higher proportion of patients receiving ruxolitinib (1.5%/0.75%) vs vehicle achieved itch numerical rating scale (NRS) score of 0/1 as early as within 2 days (19.0%/15.4% vs 4.6%), with improvements sustained till week 8 (49.5%/43.9% vs 18.3%; all P < .05). The median time to achieve itch NRS 0/1 was <15 days with ruxolitinib cream and not estimable with the vehicle.

Study details: Findings are from a pooled analysis of two phase 3 studies, TRuE-AD1 and TruE-AD2, including 1208 patients with AD and itch NRS score of >1 who were randomly assigned to receive ruxolitinib cream or vehicle.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants, or receiving research grants or honoraria from several sources, including Incyte.

Source: Blauvelt A et al. Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: Pooled analysis from two randomized phase 3 studies. J Am Acad Dermatol. 2022 (Sep 13). Doi: 10.1016/j.jaad.2022.09.010

Key clinical point: Patients with atopic dermatitis (AD) who received ruxolitinib achieved an itch-free state within 2 days, which was maintained throughout the 8-week treatment period.

Major finding: A significantly higher proportion of patients receiving ruxolitinib (1.5%/0.75%) vs vehicle achieved itch numerical rating scale (NRS) score of 0/1 as early as within 2 days (19.0%/15.4% vs 4.6%), with improvements sustained till week 8 (49.5%/43.9% vs 18.3%; all P < .05). The median time to achieve itch NRS 0/1 was <15 days with ruxolitinib cream and not estimable with the vehicle.

Study details: Findings are from a pooled analysis of two phase 3 studies, TRuE-AD1 and TruE-AD2, including 1208 patients with AD and itch NRS score of >1 who were randomly assigned to receive ruxolitinib cream or vehicle.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants, or receiving research grants or honoraria from several sources, including Incyte.

Source: Blauvelt A et al. Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: Pooled analysis from two randomized phase 3 studies. J Am Acad Dermatol. 2022 (Sep 13). Doi: 10.1016/j.jaad.2022.09.010

Key clinical point: Patients with atopic dermatitis (AD) who received ruxolitinib achieved an itch-free state within 2 days, which was maintained throughout the 8-week treatment period.

Major finding: A significantly higher proportion of patients receiving ruxolitinib (1.5%/0.75%) vs vehicle achieved itch numerical rating scale (NRS) score of 0/1 as early as within 2 days (19.0%/15.4% vs 4.6%), with improvements sustained till week 8 (49.5%/43.9% vs 18.3%; all P < .05). The median time to achieve itch NRS 0/1 was <15 days with ruxolitinib cream and not estimable with the vehicle.

Study details: Findings are from a pooled analysis of two phase 3 studies, TRuE-AD1 and TruE-AD2, including 1208 patients with AD and itch NRS score of >1 who were randomly assigned to receive ruxolitinib cream or vehicle.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants, or receiving research grants or honoraria from several sources, including Incyte.

Source: Blauvelt A et al. Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: Pooled analysis from two randomized phase 3 studies. J Am Acad Dermatol. 2022 (Sep 13). Doi: 10.1016/j.jaad.2022.09.010

Key clinical point: Dupilumab reduced disease severity and showed a tolerable safety profile in children with moderate-to-severe atopic dermatitis (AD) as young as 6 months.

Major finding: At week 16, a significantly higher proportion of children receiving dupilumab vs placebo achieved the Investigator’s Global Assessment score of 0/1 (28% vs 4%; P < .0001). Both groups had a similar prevalence of adverse events (AE; 64% vs 74%), and no dupilumab-related serious AE were reported.

Study details: Findings are from the phase 3 LIBERTY AD PRESCHOOL study including 162 children between the ages of 6 months and 6 years with moderate-to-severe AD who were randomly assigned to receive subcutaneous dupilumab or placebo, both with low-potency topical corticosteroids.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Ten authors declared being current or former employees and shareholders of Regeneron Pharmaceuticals, and 5 authors declared being employees or shareholders of Sanofi. The other authors reported ties with several sources.

Source: Paller AS et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400(10356):908-919 (Sep 17). Doi: 10.1016/S0140-6736(22)01539-2

Key clinical point: Dupilumab reduced disease severity and showed a tolerable safety profile in children with moderate-to-severe atopic dermatitis (AD) as young as 6 months.

Major finding: At week 16, a significantly higher proportion of children receiving dupilumab vs placebo achieved the Investigator’s Global Assessment score of 0/1 (28% vs 4%; P < .0001). Both groups had a similar prevalence of adverse events (AE; 64% vs 74%), and no dupilumab-related serious AE were reported.

Study details: Findings are from the phase 3 LIBERTY AD PRESCHOOL study including 162 children between the ages of 6 months and 6 years with moderate-to-severe AD who were randomly assigned to receive subcutaneous dupilumab or placebo, both with low-potency topical corticosteroids.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Ten authors declared being current or former employees and shareholders of Regeneron Pharmaceuticals, and 5 authors declared being employees or shareholders of Sanofi. The other authors reported ties with several sources.

Source: Paller AS et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400(10356):908-919 (Sep 17). Doi: 10.1016/S0140-6736(22)01539-2

Key clinical point: Dupilumab reduced disease severity and showed a tolerable safety profile in children with moderate-to-severe atopic dermatitis (AD) as young as 6 months.

Major finding: At week 16, a significantly higher proportion of children receiving dupilumab vs placebo achieved the Investigator’s Global Assessment score of 0/1 (28% vs 4%; P < .0001). Both groups had a similar prevalence of adverse events (AE; 64% vs 74%), and no dupilumab-related serious AE were reported.

Study details: Findings are from the phase 3 LIBERTY AD PRESCHOOL study including 162 children between the ages of 6 months and 6 years with moderate-to-severe AD who were randomly assigned to receive subcutaneous dupilumab or placebo, both with low-potency topical corticosteroids.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals. Ten authors declared being current or former employees and shareholders of Regeneron Pharmaceuticals, and 5 authors declared being employees or shareholders of Sanofi. The other authors reported ties with several sources.

Source: Paller AS et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022;400(10356):908-919 (Sep 17). Doi: 10.1016/S0140-6736(22)01539-2

Individuals who are middle-aged and older and who sleep 5 hours or less a night may be at risk for an array of serious and chronic health conditions, ranging from heart disease to cancer, results of a large study show.

Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.

Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.

“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.

She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”

The study was published online in PLOS Medicine.
 

Risk of multiple chronic diseases

Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).

For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).

The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.

At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).

For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.

Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.

“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”

The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
 

Chicken or egg?

Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.

Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.

Dr. Gamaldo also raised the issue of sleep quality.

“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.

In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.

“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.

“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.

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

Individuals who are middle-aged and older and who sleep 5 hours or less a night may be at risk for an array of serious and chronic health conditions, ranging from heart disease to cancer, results of a large study show.

Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.

Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.

“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.

She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”

The study was published online in PLOS Medicine.
 

Risk of multiple chronic diseases

Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).

For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).

The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.

At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).

For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.

Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.

“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”

The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
 

Chicken or egg?

Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.

Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.

Dr. Gamaldo also raised the issue of sleep quality.

“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.

In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.

“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.

“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.

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

Individuals who are middle-aged and older and who sleep 5 hours or less a night may be at risk for an array of serious and chronic health conditions, ranging from heart disease to cancer, results of a large study show.

Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.

Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.

“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.

She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”

The study was published online in PLOS Medicine.
 

Risk of multiple chronic diseases

Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).

For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).

The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.

At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).

For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.

Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.

“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”

The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
 

Chicken or egg?

Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.

Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.

Dr. Gamaldo also raised the issue of sleep quality.

“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.

In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.

“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.

“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.

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

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

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

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

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

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

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

Most adolescents with gender dysphoria who took puberty-blocking drugs for at least 3 months and then progressed to cross-sex hormone treatment were still taking hormones as they entered adulthood, new research of patients at a pioneering Dutch clinic shows.

The study negates past findings that large numbers of youth regret transitioning, say Maria Anna Theodora Catharina van der Loos, MD, and colleagues from the Centre of Expertise on Gender Dysphoria, Amsterdam, in their article published online in The Lancet Child & Adolescent Health. They believe the difference between their findings and those of other studies lies in proper diagnostic evaluation.

“The study aims to demonstrate, with a methodology that is more than adequate, that transgender people who begin their transition in childhood-adolescence do not give up,” Adrián Carrasco Munera, MD, a specialist in family and community medicine and member of the LGTBIQ+ Health Group of the Madrid Society of Family and Community Medicine told the UK Science Media Centre.

The cohort included 720 youth: 220 (31%) were assigned male at birth (AMAB) and 500 (69%) were assigned female at birth (AFAB). At the start of puberty-blocking treatment with a gonadotrophin-releasing hormone agonist, the median age of patients was 14.1 years for AMAB and 16.0 years for AFAB.

Of that cohort, 704 (98%) continued hormone therapy to the end of data collection (Dec. 31, 2018), at which point the median age of patients was 20 years for AMAB and 19 years for AFAB.

Careful consideration of patient needs

All the patients received care at the “Dutch Clinic,” which more than 20 years ago pioneered the approach of giving puberty-blocking drugs to children looking to transition, followed by cross-sex hormones. The study includes the “complete adolescent population” at the facility who met the inclusion criteria.

A similar U.S. study published earlier this year found that 74.4% of individuals who had started gender-affirming hormones before age 18 were still on them 4 years after starting medical treatment.

“However, it is unclear how many of these adolescents [in the U.S. study] used puberty-suppressing treatment before gender-affirming hormone treatment and to what extent they underwent diagnostic evaluation before initiation of medical treatment,” say Dr. van der Loos and colleagues.

She told this news organization that her clinic provides “a thorough diagnostic and mental health assessment” and discussion of fertility preservation prior to any youth being prescribed puberty blockers or cross-sex hormones.

About 40% of adolescents assessed by the gender clinic in Amsterdam go on to receive hormonal treatment.

“The gender identity unit of the Amsterdam UMC is a world leader in all aspects of transgender medicine and is governed by protocolized actions. This is reflected in the quality of the data and methodology of the study, and therefore of its conclusions,” endocrinologist Gilberto Pérez López, MD, Gregorio Marañón General University Hospital, Madrid, told the UK Science Media Centre.

“These findings can and should help and guide the current public and legal debate on the initiation of medical treatment in transgender minors.”

However, he cautioned the study is limited by the fact that the data come from a registry and they looked at only prescriptions issued and not compliance.

Another interesting thing to note in the research is that almost 70% of patients were born girls and they presented at the gender clinics later in adolescence than the natal boys.

“We don’t have a sound reason for this,” Dr. van der Loos noted.

Study limitations

She also acknowledges that the short follow-up data in some individuals make it difficult to draw conclusions about regret, to some extent.

The average use of cross-sex hormones in their study was 3.5 years for males transitioning to females and 2.3 years for females transitioning to males, so on average, this wouldn’t be long enough to see regret, she acknowledged.

Prior research shows that if youth decide to detransition to their natal sex, this can take, on average, 5 years from the start of medical therapy among born females and 7 years among born males.

However, some born males in the study had been taking hormones for 20 years and some natal females for 15 years, said Dr. van der Loos.

Another limitation is that the research only followed individuals until the end of 2018 while some government data estimate that the number of teens identifying as transgender has nearly doubled over the past 5 years.

The authors, Dr. Munera, and Dr. Lopez have reported no relevant financial relationships.

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

Most adolescents with gender dysphoria who took puberty-blocking drugs for at least 3 months and then progressed to cross-sex hormone treatment were still taking hormones as they entered adulthood, new research of patients at a pioneering Dutch clinic shows.

The study negates past findings that large numbers of youth regret transitioning, say Maria Anna Theodora Catharina van der Loos, MD, and colleagues from the Centre of Expertise on Gender Dysphoria, Amsterdam, in their article published online in The Lancet Child & Adolescent Health. They believe the difference between their findings and those of other studies lies in proper diagnostic evaluation.

“The study aims to demonstrate, with a methodology that is more than adequate, that transgender people who begin their transition in childhood-adolescence do not give up,” Adrián Carrasco Munera, MD, a specialist in family and community medicine and member of the LGTBIQ+ Health Group of the Madrid Society of Family and Community Medicine told the UK Science Media Centre.

The cohort included 720 youth: 220 (31%) were assigned male at birth (AMAB) and 500 (69%) were assigned female at birth (AFAB). At the start of puberty-blocking treatment with a gonadotrophin-releasing hormone agonist, the median age of patients was 14.1 years for AMAB and 16.0 years for AFAB.

Of that cohort, 704 (98%) continued hormone therapy to the end of data collection (Dec. 31, 2018), at which point the median age of patients was 20 years for AMAB and 19 years for AFAB.

Careful consideration of patient needs

All the patients received care at the “Dutch Clinic,” which more than 20 years ago pioneered the approach of giving puberty-blocking drugs to children looking to transition, followed by cross-sex hormones. The study includes the “complete adolescent population” at the facility who met the inclusion criteria.

A similar U.S. study published earlier this year found that 74.4% of individuals who had started gender-affirming hormones before age 18 were still on them 4 years after starting medical treatment.

“However, it is unclear how many of these adolescents [in the U.S. study] used puberty-suppressing treatment before gender-affirming hormone treatment and to what extent they underwent diagnostic evaluation before initiation of medical treatment,” say Dr. van der Loos and colleagues.

She told this news organization that her clinic provides “a thorough diagnostic and mental health assessment” and discussion of fertility preservation prior to any youth being prescribed puberty blockers or cross-sex hormones.

About 40% of adolescents assessed by the gender clinic in Amsterdam go on to receive hormonal treatment.

“The gender identity unit of the Amsterdam UMC is a world leader in all aspects of transgender medicine and is governed by protocolized actions. This is reflected in the quality of the data and methodology of the study, and therefore of its conclusions,” endocrinologist Gilberto Pérez López, MD, Gregorio Marañón General University Hospital, Madrid, told the UK Science Media Centre.

“These findings can and should help and guide the current public and legal debate on the initiation of medical treatment in transgender minors.”

However, he cautioned the study is limited by the fact that the data come from a registry and they looked at only prescriptions issued and not compliance.

Another interesting thing to note in the research is that almost 70% of patients were born girls and they presented at the gender clinics later in adolescence than the natal boys.

“We don’t have a sound reason for this,” Dr. van der Loos noted.

Study limitations

She also acknowledges that the short follow-up data in some individuals make it difficult to draw conclusions about regret, to some extent.

The average use of cross-sex hormones in their study was 3.5 years for males transitioning to females and 2.3 years for females transitioning to males, so on average, this wouldn’t be long enough to see regret, she acknowledged.

Prior research shows that if youth decide to detransition to their natal sex, this can take, on average, 5 years from the start of medical therapy among born females and 7 years among born males.

However, some born males in the study had been taking hormones for 20 years and some natal females for 15 years, said Dr. van der Loos.

Another limitation is that the research only followed individuals until the end of 2018 while some government data estimate that the number of teens identifying as transgender has nearly doubled over the past 5 years.

The authors, Dr. Munera, and Dr. Lopez have reported no relevant financial relationships.

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

Most adolescents with gender dysphoria who took puberty-blocking drugs for at least 3 months and then progressed to cross-sex hormone treatment were still taking hormones as they entered adulthood, new research of patients at a pioneering Dutch clinic shows.

The study negates past findings that large numbers of youth regret transitioning, say Maria Anna Theodora Catharina van der Loos, MD, and colleagues from the Centre of Expertise on Gender Dysphoria, Amsterdam, in their article published online in The Lancet Child & Adolescent Health. They believe the difference between their findings and those of other studies lies in proper diagnostic evaluation.

“The study aims to demonstrate, with a methodology that is more than adequate, that transgender people who begin their transition in childhood-adolescence do not give up,” Adrián Carrasco Munera, MD, a specialist in family and community medicine and member of the LGTBIQ+ Health Group of the Madrid Society of Family and Community Medicine told the UK Science Media Centre.

The cohort included 720 youth: 220 (31%) were assigned male at birth (AMAB) and 500 (69%) were assigned female at birth (AFAB). At the start of puberty-blocking treatment with a gonadotrophin-releasing hormone agonist, the median age of patients was 14.1 years for AMAB and 16.0 years for AFAB.

Of that cohort, 704 (98%) continued hormone therapy to the end of data collection (Dec. 31, 2018), at which point the median age of patients was 20 years for AMAB and 19 years for AFAB.

Careful consideration of patient needs

All the patients received care at the “Dutch Clinic,” which more than 20 years ago pioneered the approach of giving puberty-blocking drugs to children looking to transition, followed by cross-sex hormones. The study includes the “complete adolescent population” at the facility who met the inclusion criteria.

A similar U.S. study published earlier this year found that 74.4% of individuals who had started gender-affirming hormones before age 18 were still on them 4 years after starting medical treatment.

“However, it is unclear how many of these adolescents [in the U.S. study] used puberty-suppressing treatment before gender-affirming hormone treatment and to what extent they underwent diagnostic evaluation before initiation of medical treatment,” say Dr. van der Loos and colleagues.

She told this news organization that her clinic provides “a thorough diagnostic and mental health assessment” and discussion of fertility preservation prior to any youth being prescribed puberty blockers or cross-sex hormones.

About 40% of adolescents assessed by the gender clinic in Amsterdam go on to receive hormonal treatment.

“The gender identity unit of the Amsterdam UMC is a world leader in all aspects of transgender medicine and is governed by protocolized actions. This is reflected in the quality of the data and methodology of the study, and therefore of its conclusions,” endocrinologist Gilberto Pérez López, MD, Gregorio Marañón General University Hospital, Madrid, told the UK Science Media Centre.

“These findings can and should help and guide the current public and legal debate on the initiation of medical treatment in transgender minors.”

However, he cautioned the study is limited by the fact that the data come from a registry and they looked at only prescriptions issued and not compliance.

Another interesting thing to note in the research is that almost 70% of patients were born girls and they presented at the gender clinics later in adolescence than the natal boys.

“We don’t have a sound reason for this,” Dr. van der Loos noted.

Study limitations

She also acknowledges that the short follow-up data in some individuals make it difficult to draw conclusions about regret, to some extent.

The average use of cross-sex hormones in their study was 3.5 years for males transitioning to females and 2.3 years for females transitioning to males, so on average, this wouldn’t be long enough to see regret, she acknowledged.

Prior research shows that if youth decide to detransition to their natal sex, this can take, on average, 5 years from the start of medical therapy among born females and 7 years among born males.

However, some born males in the study had been taking hormones for 20 years and some natal females for 15 years, said Dr. van der Loos.

Another limitation is that the research only followed individuals until the end of 2018 while some government data estimate that the number of teens identifying as transgender has nearly doubled over the past 5 years.

The authors, Dr. Munera, and Dr. Lopez have reported no relevant financial relationships.

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

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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

VIENNA – Prescription drugs designed to boost cognition in neurodevelopmental disorders do not increase overall cognitive performance in healthy individuals – and may even reduce productivity, new research suggests.

In a randomized controlled trial, 40 healthy adults were given the attention-deficit/hyperactivity disorder (ADHD) treatments methylphenidate or dexamphetamine or the wakefulness-promoting drug modafinil vs. placebo.

While receiving the so-called “smart drugs,” participants spent more time and made more moves more quickly while solving each problem on a complex cognitive task than when given the placebo. But with no significant improvement in overall performance, all drugs were associated with a significant reduction in efficiency.

The findings “reinforce the idea that, while the drugs administered were motivational, the resulting increase in effort came at a cost in the loss of productivity,” said study presenter David Coghill, MD, PhD, chair of developmental mental health, the University of Melbourne.

This was especially true for individuals who scored high when receiving placebo, “who ended up producing below average productivity when on the drugs,” he noted.

“Overall, these drugs don’t increase the performance. Instead, they cause a regression to the mean, and appear to have a more negative effect on those who performed best at baseline,” Dr. Coghill added.

He presented the findings at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

Past evidence ambiguous

Dr. Coghill noted that prescription-only stimulant drugs are increasingly used by employees and students as “smart drugs” to enhance workplace or academic productivity.

He conducted the study with colleagues from the department of economics at his institution, because of “their interest in people using cognitive enhancers within the financial industry, in the hope that that would increase their productivity in what is a very competitive industry on the floor of the trading rooms.”

However, while “there’s a subjective belief” that these drugs are effective as cognitive enhancers, the evidence to actually demonstrate that in healthy individuals “is, at best, ambiguous,” he told meeting attendees.

Improvements in cognitive capacities, such as working memory and improved planning, are most evident in clinical populations such as those with ADHD, which could be due to a “ceiling effect” of the cognitive tasks in healthy individuals, Dr. Coghill noted.

To investigate further, the researchers conducted a randomized, double-blinded trial of standard adult doses of methylphenidate (30 mg), dexamphetamine (15 mg), and modafinil (200 mg) vs. placebo. The healthy participants (n = 40), all of whom were aged 18-35 years, crossed to each of the other treatment groups over the course of four intervention sessions.

All were asked to solve eight instances of the knapsack task, the aim of which is to place theoretical objects in a knapsack to achieve the maximum value within a certain weight limit.

“This looks very simple but as the number of items increases, it becomes incredibly complex to compute, and actually is not computable using standard approaches. You have to deal with trial and error,” Dr. Coghill said.

The participants also completed several CANTAB cognitive tasks.

‘Surprising’ findings

Results showed that, overall, the drugs did not have a significant effect on task performance (slope = –0.16; P = .011).

Moreover, the drugs, both individually and collectively, had a significant negative effect on the value attained during any one attempt at the knapsack task (slope = –0.003; P = .02), an effect that extended “across the whole range” of task complexity, Dr. Coghill reported.

He went on to show that “participants actually looked as if they were working harder” when they took the three active drugs than when they were given a placebo. They also “spent more time solving each problem,” he added.

When taking the active drugs, participants made more moves during each task than when taking placebo, and made their moves more quickly.

“So these medications increased motivation,” Dr. Coghill said. “If you were sitting [and] watching this person, you would think that they were working harder.”

Yet their productivity, defined as the average gain in value per move on the knapsack task, was lower. Regression analysis identified a “significant and sizable drop in productivity” vs. placebo, Dr. Coghill noted.

This was the case for methylphenidate (P < .001), dexamphetamine (P < .001), and modafinil (P < .05), “whether you looked at the mean or median performance,” he said.

“Breaking it down a little bit more, when you looked at the individual participant level, you find substantial heterogeneity across participants,” noted Dr. Coghill.

“More than that, we found a significant negative correlation between productivity under methylphenidate compared to productivity under placebo, and this suggests a regression to the mean,” with participants who performed better under placebo performing worse with methylphenidate, he explained.

While the relationship was “exactly the same with modafinil,” it was not found with dexamphetamine, with a strong negative correlation between the productivity effects between dexamphetamine and methylphenidate (slope = –0.29; P < .0001).

“This is surprising because we assume that methylphenidate and dexamphetamine are working in very similar ways,” Dr. Coghill said.
 

Time to rethink, rewind?

Commenting for this article, session chair John F. Cryan, PhD, department of anatomy and neuroscience, University College Cork, Ireland, said that, based on the current data, “we might need to rethink [how] ‘smart’ psychopharmacological agents are.”

Dr. Cryan, chair of the ECNP Scientific Program Committee, added that there may be a need to revisit the difficulty of different types of cognitive tasks used in studies assessing the abilities of cognitive enhancing drugs and to “rewind conventional wisdom” around them.

Also commenting, Andrew Westbrook, PhD, of the department of cognitive linguistics and psychological sciences, Brown University, Providence, R.I., said the results seem “reasonable” and are “consistent with my own perspective.”

However, he told this news organization, “some caveats are warranted,” not least that the context of the task can have an impact on the results it obtains.

“We have hypothesized that pharmacologically-enhanced striatal dopamine signaling can boost a kind of cognitive impulsivity, leading to errors and diminished performance, especially for people who already have high striatal dopamine functioning.”

He added that this impulsivity can also lead to errors “in situations where there are highly likely actions, thoughts, or behaviors” in a task, “which they would have to override to be successful” in performing it.

Dr. Westbrook gave the example of the “Stroop task where you are presented with words presented in some color ink and your job is to name the color of the ink but not read the word.”

If the word “green,” for example, was presented in green ink, “you may have no trouble naming the ink color,” but if it was presented in red ink “then you may impulsively read the word, because that is what we normally do with words. 

“Overriding this kind of habitual action can be particularly slippery business when striatal dopamine signaling is pharmacologically enhanced,” Dr. Westbrook said.

No funding for the study was reported. Dr. Coghill reported relationships with Medice, Novartis, Servier, Takeda/Shire Cambridge University Press, and Oxford University Press.

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