Federal Practitioner

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

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

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

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

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

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

TOPLINE:

Updated data from the OPRA trial show that nearly half of patients with stage II/III rectal cancer treated with total neoadjuvant therapy preserved their rectums over 5 years, with local tumor regrowth occurring mostly within the first 2 years.

METHODOLOGY:

• Many patients with locally advanced rectal cancer treated with total neoadjuvant therapy in the OPRA trial achieved a complete or near-complete tumor response and were initially offered a watch-and-wait strategy.
• However, nearly one-third of patients receiving watch-and-wait developed local tumor regrowth and ultimately required total mesorectal excision (TME).
• The study team reported updated organ preservation rates and oncologic outcomes in the OPRA trial of 324 patients with stage II/III rectal cancer randomized to induction chemotherapy followed by chemoradiation (n = 158) or chemoradiation followed by consolidation chemotherapy (n = 166).
• Among the 304 patients restaged a median of 7.8 weeks after finishing total neoadjuvant therapy, investigators recommended TME in 26% and watch-and-wait in 74% (n = 225).

TAKEAWAY:

• The researchers reported similar 5-year disease-free survival among patients in the induction chemotherapy group (71%) and the consolidation chemotherapy group (69%). The estimated 5-year overall survival rates were also similar in the two groups – 88% in the induction group vs. 85% in the consolidation group.
• Among the patients who received watch-and-wait, 36% (n = 81) experienced tumor regrowth; 94% occurred within 2 years and 99% occurred within 3 years.
• An estimated 39% of patients in the induction chemotherapy group and 54% in the consolidation chemotherapy group achieved organ preservation at 5 years, representing about half of patients overall.
• Among the patients who received watch-and-wait, salvage TME following tumor regrowth appeared to offer disease-free survival (64% of patients) similar to immediate TME after incomplete response to total neoadjuvant therapy (also 64%).

IN PRACTICE:

Total neoadjuvant therapy among patients with rectal cancer “resulted in long-term organ preservation in half of the patients,” the authors concluded. Although the order of therapy did not affect survival, consolidation chemotherapy “resulted in higher organ preservation at 5 years.”

“Our results support the recommendation that patients with rectal cancer offered [watch-and-wait] after neoadjuvant therapy should have very close surveillance during the first 3 years,” the authors added.
 

SOURCE:

The study, with first author Floris S. Verheij, BSc, Memorial Sloan Kettering Cancer Center, New York, was published online Oct. 26, 2023, in the Journal of Clinical Oncology.

LIMITATIONS:

The study, published as a clinical trials update, does not include a discussion of limitations.

DISCLOSURES:

Funding was provided by the National Cancer Institute. Several OPRA trialists disclosed relationships with a range of companies, including Sironax, Janssen Oncology, Toray Industries, Merck, and Intuitive Surgical.

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

TOPLINE:

Updated data from the OPRA trial show that nearly half of patients with stage II/III rectal cancer treated with total neoadjuvant therapy preserved their rectums over 5 years, with local tumor regrowth occurring mostly within the first 2 years.

METHODOLOGY:

• Many patients with locally advanced rectal cancer treated with total neoadjuvant therapy in the OPRA trial achieved a complete or near-complete tumor response and were initially offered a watch-and-wait strategy.
• However, nearly one-third of patients receiving watch-and-wait developed local tumor regrowth and ultimately required total mesorectal excision (TME).
• The study team reported updated organ preservation rates and oncologic outcomes in the OPRA trial of 324 patients with stage II/III rectal cancer randomized to induction chemotherapy followed by chemoradiation (n = 158) or chemoradiation followed by consolidation chemotherapy (n = 166).
• Among the 304 patients restaged a median of 7.8 weeks after finishing total neoadjuvant therapy, investigators recommended TME in 26% and watch-and-wait in 74% (n = 225).

TAKEAWAY:

• The researchers reported similar 5-year disease-free survival among patients in the induction chemotherapy group (71%) and the consolidation chemotherapy group (69%). The estimated 5-year overall survival rates were also similar in the two groups – 88% in the induction group vs. 85% in the consolidation group.
• Among the patients who received watch-and-wait, 36% (n = 81) experienced tumor regrowth; 94% occurred within 2 years and 99% occurred within 3 years.
• An estimated 39% of patients in the induction chemotherapy group and 54% in the consolidation chemotherapy group achieved organ preservation at 5 years, representing about half of patients overall.
• Among the patients who received watch-and-wait, salvage TME following tumor regrowth appeared to offer disease-free survival (64% of patients) similar to immediate TME after incomplete response to total neoadjuvant therapy (also 64%).

IN PRACTICE:

Total neoadjuvant therapy among patients with rectal cancer “resulted in long-term organ preservation in half of the patients,” the authors concluded. Although the order of therapy did not affect survival, consolidation chemotherapy “resulted in higher organ preservation at 5 years.”

“Our results support the recommendation that patients with rectal cancer offered [watch-and-wait] after neoadjuvant therapy should have very close surveillance during the first 3 years,” the authors added.
 

SOURCE:

The study, with first author Floris S. Verheij, BSc, Memorial Sloan Kettering Cancer Center, New York, was published online Oct. 26, 2023, in the Journal of Clinical Oncology.

LIMITATIONS:

The study, published as a clinical trials update, does not include a discussion of limitations.

DISCLOSURES:

Funding was provided by the National Cancer Institute. Several OPRA trialists disclosed relationships with a range of companies, including Sironax, Janssen Oncology, Toray Industries, Merck, and Intuitive Surgical.

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

TOPLINE:

Updated data from the OPRA trial show that nearly half of patients with stage II/III rectal cancer treated with total neoadjuvant therapy preserved their rectums over 5 years, with local tumor regrowth occurring mostly within the first 2 years.

METHODOLOGY:

• Many patients with locally advanced rectal cancer treated with total neoadjuvant therapy in the OPRA trial achieved a complete or near-complete tumor response and were initially offered a watch-and-wait strategy.
• However, nearly one-third of patients receiving watch-and-wait developed local tumor regrowth and ultimately required total mesorectal excision (TME).
• The study team reported updated organ preservation rates and oncologic outcomes in the OPRA trial of 324 patients with stage II/III rectal cancer randomized to induction chemotherapy followed by chemoradiation (n = 158) or chemoradiation followed by consolidation chemotherapy (n = 166).
• Among the 304 patients restaged a median of 7.8 weeks after finishing total neoadjuvant therapy, investigators recommended TME in 26% and watch-and-wait in 74% (n = 225).

TAKEAWAY:

• The researchers reported similar 5-year disease-free survival among patients in the induction chemotherapy group (71%) and the consolidation chemotherapy group (69%). The estimated 5-year overall survival rates were also similar in the two groups – 88% in the induction group vs. 85% in the consolidation group.
• Among the patients who received watch-and-wait, 36% (n = 81) experienced tumor regrowth; 94% occurred within 2 years and 99% occurred within 3 years.
• An estimated 39% of patients in the induction chemotherapy group and 54% in the consolidation chemotherapy group achieved organ preservation at 5 years, representing about half of patients overall.
• Among the patients who received watch-and-wait, salvage TME following tumor regrowth appeared to offer disease-free survival (64% of patients) similar to immediate TME after incomplete response to total neoadjuvant therapy (also 64%).

IN PRACTICE:

Total neoadjuvant therapy among patients with rectal cancer “resulted in long-term organ preservation in half of the patients,” the authors concluded. Although the order of therapy did not affect survival, consolidation chemotherapy “resulted in higher organ preservation at 5 years.”

“Our results support the recommendation that patients with rectal cancer offered [watch-and-wait] after neoadjuvant therapy should have very close surveillance during the first 3 years,” the authors added.
 

SOURCE:

The study, with first author Floris S. Verheij, BSc, Memorial Sloan Kettering Cancer Center, New York, was published online Oct. 26, 2023, in the Journal of Clinical Oncology.

LIMITATIONS:

The study, published as a clinical trials update, does not include a discussion of limitations.

DISCLOSURES:

Funding was provided by the National Cancer Institute. Several OPRA trialists disclosed relationships with a range of companies, including Sironax, Janssen Oncology, Toray Industries, Merck, and Intuitive Surgical.

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

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Longer cumulative use of medication to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a small, but statistically significant, increased risk for cardiovascular disease (CVD), results of a large Swedish nested case-control study suggest.

The increased risk was evident only for hypertension and arterial disease, was dose dependent, and was higher for stimulant than nonstimulant ADHD medications.

“Clinicians should be vigilant in monitoring signs and symptoms of cardiovascular diseases, particularly among those receiving higher doses,” Zheng Chang, PhD, principal researcher, department of medical epidemiology and biostatistics, Karolinska Institutet, Stockholm, said in an interview.

“Treatment decisions, as always, should be based on careful weighing of potential benefits and risks at individual patient level, rather than simple one-size-fits-all recommendations,” Dr. Chang added.

The study was published online in JAMA Psychiatry

Filling in the research gaps

The use of medications to treat ADHD has increased markedly over the past decades in both children and adults. The potential risk for CVD associated with long-term ADHD medication use remains unclear. Most “longitudinal” studies that have looked at the association have an average follow-up time of no more than 2 years, the authors note.

In contrast, the Swedish study assessed the association between cumulative use of ADHD medication in children and adults followed for up to 14 years and also looked at whether associations differ across types of medication and dosages, types of CVD, gender, and age.

Among 278,027 individuals aged 6-64 years diagnosed with ADHD or dispensed ADHD medication, 10,388 with CVD were identified and matched to 51,672 controls without CVD.

Longer cumulative duration of ADHD medication use was associated with a statistically significant increased risk for CVD, compared with no use.

When the risk for specific CVDs was examined, long-term use of ADHD medication (compared with no use) was associated with an increased risk for hypertension and arterial disease but not arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

For hypertension, the adjusted odds ratio was 1.72 (95% confidence interval, 1.51-1.97) for 3 to ≤ 5 years and 1.80 (95% CI, 1.55-2.08) for > 5 years of medication use. For arterial disease, the AOR was 1.65 (95% CI, 1.11-2.45) for 3 to ≤ 5 years and 1.49 (95% CI, 0.96-2.32) for > 5 years of use.
 

Stimulants confer greatest risk

Across the 14-year follow-up period, each additional year of ADHD medication use was associated with an average 4% increased CVD risk, with a larger 8% increased risk in the first 3 years of cumulative use, followed by stable risk over the remaining follow-up.

Similar risks were observed in children and adults, as well as in females and males.

When focusing on specific ADHD medications, compared with no use, long-term use of the stimulant methylphenidate was associated with an increased risk for CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤ 5 years and 1.19 [95% CI, 1.08-1.31] for > 5 years).

The same was true for long-term use of the stimulant lisdexamfetamine (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤ 3 years and 1.17 [95% CI, 0.98-1.40] for > 3 years).

In contrast, use of the nonstimulant atomoxetine was associated with elevated CVD risk only for the first year of use (AOR, 1.07; 95% CI, 1.01-1.13).

The increased risk for CVD occurred only above certain average daily doses: 45 mg for methylphenidate and lisdexamfetamine, 22.5 mg for amphetamines, and 120 mg for atomoxetine.

The authors note that, although they accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, they could not prove causality.

‘Tricky trade-offs’

The coauthors of an editorial in JAMA Psychiatry (2023 Nov 22. doi: 10.1001/jamapsychiatry.2023.4126) note that the study “should remind us that clinical decision-making is often based on tricky trade-offs that should be considered at the individual patient level.”

Given that hypertension is the leading cause of CV morbidity and mortality worldwide, the increased likelihood of hypertension with long-term use of ADHD medications “cannot be disregarded,” write Samuele Cortese, MD, PhD, and Cristiano Fava, MD, PhD, with University of Southampton (England).

“These findings are especially relevant given the reported association between ADHD and physical conditions, such as obesity, which further contribute to increased cardiovascular risk,” they add.

Dr. Cortese and Dr. Fava say that the increased CV risk – averaging 4% per year and stabilizing after 3 years of treatment – “should be carefully weighed against the established benefits, on a case-by-case basis.”

“Importantly,” they write, “large real-world self-controlled studies have shown that individuals with ADHD experience significantly fewer unintentional physical injuries, motor vehicle crashes, substance use disorders, and criminal acts, as well as improved academic functioning, during periods when they are taking, compared with periods when they are not taking, methylphenidate.”

The risk-benefit ratio, however, may be lower in people with preexisting heart conditions. However, more evidence and precise recommendations are needed in relation to the treatment of individuals with ADHD and preexisting CV conditions, the editorial writers say.

This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare and the European Union’s Horizon 2020 research and innovation program. The authors and editorial writers have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

I have a long history of being interested in conversations that others avoid. In medical school, I felt that we didn’t talk enough about death, so I organized a lecture series on end-of-life care for my fellow students. Now, as a sexual medicine specialist, I have other conversations from which many medical providers shy away. So, buckle up! Here’s a topic that rarely emerges in medical care: sexuality at the end of life.

A key question in palliative care is: How do you want to live the life you have left? And where does the wide range of human pleasures fit in? In her book The Pleasure Zone, sex therapist Stella Resnick describes eight kinds of pleasure:

• pain relief
• play, humor, movement, and sound
• mental
• emotional
• sensual
• spiritual
• primal (just being)
• sexual

At the end of life, both medically and culturally, we pay attention to many of these pleasures. But sexuality is often ignored.

Sexuality – which can be defined as the experience of oneself as a sexual being – may include how sex is experienced in relationships or with oneself, sexual orientation, body image, gender expression and identity, as well as sexual satisfaction and pleasure. People may have different priorities at different times regarding their sexuality, but sexuality is a key aspect of feeling fully alive and human across the lifespan. At the end of life, sexuality, sexual expression, and physical connection may play even more important roles than previously.
 

‘I just want to be able to have sex with my husband again’

Z was a 75-year-old woman who came to me for help with vaginal stenosis. Her cancer treatments were not going well. I asked her one of my typical questions: “What does sex mean to you?”

Sexual pleasure was “glue” – a critical way for her to connect with her sense of self and with her husband, a man of few words. She described transcendent experiences with partnered sex during her life. Finally, she explained, she was saddened by the idea of not experiencing that again before she died. 

As medical providers, we don’t all need to be sex experts, but our patients should be able to have open and shame-free conversations with us about these issues at all stages of life. Up to 86% of palliative care patients want the chance to discuss their sexual concerns with a skilled clinician, and many consider this issue important to their psychological well-being. And yet, 91% reported that sexuality had not been addressed in their care.

In a Canadian study of 10 palliative care patients (and their partners), all but one felt that their medical providers should initiate conversations about sexuality and the effect of illness on sexual experience. They felt that this communication should be an integral component of care. The one person who disagreed said it was appropriate for clinicians to ask patients whether they wanted to talk about sexuality.

Before this study, sexuality had been discussed with only one participant. Here’s the magic part: Several of the patients reported that the study itself was therapeutic. This is my clinical experience as well. More often than not, open and shame-free clinical discussions about sexuality led to patients reflecting: “I’ve never been able to say this to another person, and now I feel so much better.” 

One study of palliative care nurses found that while the nurses acknowledged the importance of addressing sexuality, their way of addressing sexuality followed cultural myths and norms or relied on their own experience rather than knowledge-based guidelines. Why? One explanation could be that clinicians raised and educated in North America probably did not get adequate training on this topic. We need to do better. 

Second, cultural concepts that equate sexuality with healthy and able bodies who are partnered, young, cisgender, and heterosexual make it hard to conceive of how to relate sexuality to other bodies. We’ve been steeped in the biases of our culture.

Some medical providers avoid the topic because they feel vulnerable, fearful that a conversation about sexuality with a patient will reveal something about themselves. Others may simply deny the possibility that sexual function changes in the face of serious illness or that this could be a priority for their patients. Of course, we have a million other things to talk about – I get it.

Views on sex and sexuality affect how clinicians approach these conversations as well. A study of palliative care professionals described themes among those who did and did not address the topic. The professionals who did not discuss sexuality endorsed a narrow definition of sex based on genital sexual acts between two partners, usually heterosexual. Among these clinicians, when the issue came up, patients had raised the topic. They talked about sex using jokes and euphemisms (“are you still enjoying ‘good moments’ with your partner?”), perhaps to ease their own discomfort.

On the other hand, professionals who more frequently discussed sexuality with their patients endorsed a more holistic concept of sexuality: including genital and nongenital contact as well as nonphysical components like verbal communication and emotions. These clinicians found sexuality applicable to all individuals across the lifespan. They were more likely to initiate discussions about the effect of medications or illness on sexual function and address the need for equipment, such as a larger hospital bed.

I’m hoping that you might one day find yourself in the second group. Our patients at the end of life need our help in accessing the full range of pleasure in their lives. We need better medical education on how to help with sexual concerns when they arise (an article for another day), but we can start right now by simply initiating open, shame-free sexual health conversations. This is often the most important therapeutic intervention.

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester (N.Y.) Medical Center, has disclosed no relevant financial relationships.

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

I have a long history of being interested in conversations that others avoid. In medical school, I felt that we didn’t talk enough about death, so I organized a lecture series on end-of-life care for my fellow students. Now, as a sexual medicine specialist, I have other conversations from which many medical providers shy away. So, buckle up! Here’s a topic that rarely emerges in medical care: sexuality at the end of life.

A key question in palliative care is: How do you want to live the life you have left? And where does the wide range of human pleasures fit in? In her book The Pleasure Zone, sex therapist Stella Resnick describes eight kinds of pleasure:

• pain relief
• play, humor, movement, and sound
• mental
• emotional
• sensual
• spiritual
• primal (just being)
• sexual

At the end of life, both medically and culturally, we pay attention to many of these pleasures. But sexuality is often ignored.

Sexuality – which can be defined as the experience of oneself as a sexual being – may include how sex is experienced in relationships or with oneself, sexual orientation, body image, gender expression and identity, as well as sexual satisfaction and pleasure. People may have different priorities at different times regarding their sexuality, but sexuality is a key aspect of feeling fully alive and human across the lifespan. At the end of life, sexuality, sexual expression, and physical connection may play even more important roles than previously.
 

‘I just want to be able to have sex with my husband again’

Z was a 75-year-old woman who came to me for help with vaginal stenosis. Her cancer treatments were not going well. I asked her one of my typical questions: “What does sex mean to you?”

Sexual pleasure was “glue” – a critical way for her to connect with her sense of self and with her husband, a man of few words. She described transcendent experiences with partnered sex during her life. Finally, she explained, she was saddened by the idea of not experiencing that again before she died. 

As medical providers, we don’t all need to be sex experts, but our patients should be able to have open and shame-free conversations with us about these issues at all stages of life. Up to 86% of palliative care patients want the chance to discuss their sexual concerns with a skilled clinician, and many consider this issue important to their psychological well-being. And yet, 91% reported that sexuality had not been addressed in their care.

In a Canadian study of 10 palliative care patients (and their partners), all but one felt that their medical providers should initiate conversations about sexuality and the effect of illness on sexual experience. They felt that this communication should be an integral component of care. The one person who disagreed said it was appropriate for clinicians to ask patients whether they wanted to talk about sexuality.

Before this study, sexuality had been discussed with only one participant. Here’s the magic part: Several of the patients reported that the study itself was therapeutic. This is my clinical experience as well. More often than not, open and shame-free clinical discussions about sexuality led to patients reflecting: “I’ve never been able to say this to another person, and now I feel so much better.” 

One study of palliative care nurses found that while the nurses acknowledged the importance of addressing sexuality, their way of addressing sexuality followed cultural myths and norms or relied on their own experience rather than knowledge-based guidelines. Why? One explanation could be that clinicians raised and educated in North America probably did not get adequate training on this topic. We need to do better. 

Second, cultural concepts that equate sexuality with healthy and able bodies who are partnered, young, cisgender, and heterosexual make it hard to conceive of how to relate sexuality to other bodies. We’ve been steeped in the biases of our culture.

Some medical providers avoid the topic because they feel vulnerable, fearful that a conversation about sexuality with a patient will reveal something about themselves. Others may simply deny the possibility that sexual function changes in the face of serious illness or that this could be a priority for their patients. Of course, we have a million other things to talk about – I get it.

Views on sex and sexuality affect how clinicians approach these conversations as well. A study of palliative care professionals described themes among those who did and did not address the topic. The professionals who did not discuss sexuality endorsed a narrow definition of sex based on genital sexual acts between two partners, usually heterosexual. Among these clinicians, when the issue came up, patients had raised the topic. They talked about sex using jokes and euphemisms (“are you still enjoying ‘good moments’ with your partner?”), perhaps to ease their own discomfort.

On the other hand, professionals who more frequently discussed sexuality with their patients endorsed a more holistic concept of sexuality: including genital and nongenital contact as well as nonphysical components like verbal communication and emotions. These clinicians found sexuality applicable to all individuals across the lifespan. They were more likely to initiate discussions about the effect of medications or illness on sexual function and address the need for equipment, such as a larger hospital bed.

I’m hoping that you might one day find yourself in the second group. Our patients at the end of life need our help in accessing the full range of pleasure in their lives. We need better medical education on how to help with sexual concerns when they arise (an article for another day), but we can start right now by simply initiating open, shame-free sexual health conversations. This is often the most important therapeutic intervention.

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester (N.Y.) Medical Center, has disclosed no relevant financial relationships.

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

I have a long history of being interested in conversations that others avoid. In medical school, I felt that we didn’t talk enough about death, so I organized a lecture series on end-of-life care for my fellow students. Now, as a sexual medicine specialist, I have other conversations from which many medical providers shy away. So, buckle up! Here’s a topic that rarely emerges in medical care: sexuality at the end of life.

A key question in palliative care is: How do you want to live the life you have left? And where does the wide range of human pleasures fit in? In her book The Pleasure Zone, sex therapist Stella Resnick describes eight kinds of pleasure:

• pain relief
• play, humor, movement, and sound
• mental
• emotional
• sensual
• spiritual
• primal (just being)
• sexual

At the end of life, both medically and culturally, we pay attention to many of these pleasures. But sexuality is often ignored.

Sexuality – which can be defined as the experience of oneself as a sexual being – may include how sex is experienced in relationships or with oneself, sexual orientation, body image, gender expression and identity, as well as sexual satisfaction and pleasure. People may have different priorities at different times regarding their sexuality, but sexuality is a key aspect of feeling fully alive and human across the lifespan. At the end of life, sexuality, sexual expression, and physical connection may play even more important roles than previously.
 

‘I just want to be able to have sex with my husband again’

Z was a 75-year-old woman who came to me for help with vaginal stenosis. Her cancer treatments were not going well. I asked her one of my typical questions: “What does sex mean to you?”

Sexual pleasure was “glue” – a critical way for her to connect with her sense of self and with her husband, a man of few words. She described transcendent experiences with partnered sex during her life. Finally, she explained, she was saddened by the idea of not experiencing that again before she died. 

As medical providers, we don’t all need to be sex experts, but our patients should be able to have open and shame-free conversations with us about these issues at all stages of life. Up to 86% of palliative care patients want the chance to discuss their sexual concerns with a skilled clinician, and many consider this issue important to their psychological well-being. And yet, 91% reported that sexuality had not been addressed in their care.

In a Canadian study of 10 palliative care patients (and their partners), all but one felt that their medical providers should initiate conversations about sexuality and the effect of illness on sexual experience. They felt that this communication should be an integral component of care. The one person who disagreed said it was appropriate for clinicians to ask patients whether they wanted to talk about sexuality.

Before this study, sexuality had been discussed with only one participant. Here’s the magic part: Several of the patients reported that the study itself was therapeutic. This is my clinical experience as well. More often than not, open and shame-free clinical discussions about sexuality led to patients reflecting: “I’ve never been able to say this to another person, and now I feel so much better.” 

One study of palliative care nurses found that while the nurses acknowledged the importance of addressing sexuality, their way of addressing sexuality followed cultural myths and norms or relied on their own experience rather than knowledge-based guidelines. Why? One explanation could be that clinicians raised and educated in North America probably did not get adequate training on this topic. We need to do better. 

Second, cultural concepts that equate sexuality with healthy and able bodies who are partnered, young, cisgender, and heterosexual make it hard to conceive of how to relate sexuality to other bodies. We’ve been steeped in the biases of our culture.

Some medical providers avoid the topic because they feel vulnerable, fearful that a conversation about sexuality with a patient will reveal something about themselves. Others may simply deny the possibility that sexual function changes in the face of serious illness or that this could be a priority for their patients. Of course, we have a million other things to talk about – I get it.

Views on sex and sexuality affect how clinicians approach these conversations as well. A study of palliative care professionals described themes among those who did and did not address the topic. The professionals who did not discuss sexuality endorsed a narrow definition of sex based on genital sexual acts between two partners, usually heterosexual. Among these clinicians, when the issue came up, patients had raised the topic. They talked about sex using jokes and euphemisms (“are you still enjoying ‘good moments’ with your partner?”), perhaps to ease their own discomfort.

On the other hand, professionals who more frequently discussed sexuality with their patients endorsed a more holistic concept of sexuality: including genital and nongenital contact as well as nonphysical components like verbal communication and emotions. These clinicians found sexuality applicable to all individuals across the lifespan. They were more likely to initiate discussions about the effect of medications or illness on sexual function and address the need for equipment, such as a larger hospital bed.

I’m hoping that you might one day find yourself in the second group. Our patients at the end of life need our help in accessing the full range of pleasure in their lives. We need better medical education on how to help with sexual concerns when they arise (an article for another day), but we can start right now by simply initiating open, shame-free sexual health conversations. This is often the most important therapeutic intervention.

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester (N.Y.) Medical Center, has disclosed no relevant financial relationships.

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

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

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

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

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

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

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

In 2020, 54 million U.S. adults with chronic pain managed their symptoms with a mix of medication and nonpharmacologic therapies but one in four relied on medication alone, data from the Centers for Disease Control and Prevention show.

Results from the annual National Health Interview Survey (NHIS) show that over-the-counter (OTC) pain relievers were the most commonly used pharmacologic treatment and exercise was the most common choice among nonpharmacologic options.

The results also revealed that prescription opioid use for chronic pain decreased from 15.2% in 2019 to 13.5% in 2020. However, there was no corresponding increase in nonpharmacologic therapies, despite current CDC guidelines that recommend maximizing the use of medication alternatives.

“Public health efforts may reduce health inequities by increasing access to pain management therapies so that all persons with chronic pain can receive safe and effective care,” S. Michaela Rikard, PhD, and colleagues wrote.

The findings were published online in a research letter in Annals of Internal Medicine.  

Among 31,500 survey respondents, 7,400 indicated that they had pain on most days or every day for the past 3 months.

The survey collected data on self-reported opioid prescriptions in the past 3 months, as well as prescription and nonprescription opiate use during the same time period.

Among adult respondents, 60% used a combination of pharmacologic and nonpharmacologic treatments for pain and almost 27% used medications alone. Older adults, those with low incomes, uninsured individuals, and those living in the South were among those least likely to turn to nonpharmacologic treatment for pain.

After exercise, complementary therapies were the most commonly used nonpharmacologic options, including massage, meditation, or guided imagery, and spinal manipulation or other forms of chiropractic care.

For those taking medications, 76% self-reported using OTC pain relievers for pain, followed by prescription nonopioids (31%) and prescription opioids (13.5%).

Of those who used both pharmacologic and nonpharmacologic therapies, about half reported nonopioid and nonpharmacologic therapy use and 8% reported combined use of opioids, nonopioids, and nonpharmacologic therapy.

After adjustment for multiple factors, investigators found those who were older, had public insurance, or had more severe pain were more likely to use prescription opioids. They also reported severe pain (22%), but 4% reported only mild pain.

Study limitations included generalizability only to noninstitutionalized civilian adults, potential recall bias, and cross-sectional results that do not include patient or treatment history.

“Despite its limitations, this study identifies opportunities to improve guideline-concordant use of pharmacologic and nonpharmacologic therapies among adults with chronic pain,” the authors wrote.

There was no specific funding source for the study. The authors have reported no relevant financial disclosures.

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

In 2020, 54 million U.S. adults with chronic pain managed their symptoms with a mix of medication and nonpharmacologic therapies but one in four relied on medication alone, data from the Centers for Disease Control and Prevention show.

Results from the annual National Health Interview Survey (NHIS) show that over-the-counter (OTC) pain relievers were the most commonly used pharmacologic treatment and exercise was the most common choice among nonpharmacologic options.

The results also revealed that prescription opioid use for chronic pain decreased from 15.2% in 2019 to 13.5% in 2020. However, there was no corresponding increase in nonpharmacologic therapies, despite current CDC guidelines that recommend maximizing the use of medication alternatives.

“Public health efforts may reduce health inequities by increasing access to pain management therapies so that all persons with chronic pain can receive safe and effective care,” S. Michaela Rikard, PhD, and colleagues wrote.

The findings were published online in a research letter in Annals of Internal Medicine.  

Among 31,500 survey respondents, 7,400 indicated that they had pain on most days or every day for the past 3 months.

The survey collected data on self-reported opioid prescriptions in the past 3 months, as well as prescription and nonprescription opiate use during the same time period.

Among adult respondents, 60% used a combination of pharmacologic and nonpharmacologic treatments for pain and almost 27% used medications alone. Older adults, those with low incomes, uninsured individuals, and those living in the South were among those least likely to turn to nonpharmacologic treatment for pain.

After exercise, complementary therapies were the most commonly used nonpharmacologic options, including massage, meditation, or guided imagery, and spinal manipulation or other forms of chiropractic care.

For those taking medications, 76% self-reported using OTC pain relievers for pain, followed by prescription nonopioids (31%) and prescription opioids (13.5%).

Of those who used both pharmacologic and nonpharmacologic therapies, about half reported nonopioid and nonpharmacologic therapy use and 8% reported combined use of opioids, nonopioids, and nonpharmacologic therapy.

After adjustment for multiple factors, investigators found those who were older, had public insurance, or had more severe pain were more likely to use prescription opioids. They also reported severe pain (22%), but 4% reported only mild pain.

Study limitations included generalizability only to noninstitutionalized civilian adults, potential recall bias, and cross-sectional results that do not include patient or treatment history.

“Despite its limitations, this study identifies opportunities to improve guideline-concordant use of pharmacologic and nonpharmacologic therapies among adults with chronic pain,” the authors wrote.

There was no specific funding source for the study. The authors have reported no relevant financial disclosures.

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

In 2020, 54 million U.S. adults with chronic pain managed their symptoms with a mix of medication and nonpharmacologic therapies but one in four relied on medication alone, data from the Centers for Disease Control and Prevention show.

Results from the annual National Health Interview Survey (NHIS) show that over-the-counter (OTC) pain relievers were the most commonly used pharmacologic treatment and exercise was the most common choice among nonpharmacologic options.

The results also revealed that prescription opioid use for chronic pain decreased from 15.2% in 2019 to 13.5% in 2020. However, there was no corresponding increase in nonpharmacologic therapies, despite current CDC guidelines that recommend maximizing the use of medication alternatives.

“Public health efforts may reduce health inequities by increasing access to pain management therapies so that all persons with chronic pain can receive safe and effective care,” S. Michaela Rikard, PhD, and colleagues wrote.

The findings were published online in a research letter in Annals of Internal Medicine.  

Among 31,500 survey respondents, 7,400 indicated that they had pain on most days or every day for the past 3 months.

The survey collected data on self-reported opioid prescriptions in the past 3 months, as well as prescription and nonprescription opiate use during the same time period.

Among adult respondents, 60% used a combination of pharmacologic and nonpharmacologic treatments for pain and almost 27% used medications alone. Older adults, those with low incomes, uninsured individuals, and those living in the South were among those least likely to turn to nonpharmacologic treatment for pain.

After exercise, complementary therapies were the most commonly used nonpharmacologic options, including massage, meditation, or guided imagery, and spinal manipulation or other forms of chiropractic care.

For those taking medications, 76% self-reported using OTC pain relievers for pain, followed by prescription nonopioids (31%) and prescription opioids (13.5%).

Of those who used both pharmacologic and nonpharmacologic therapies, about half reported nonopioid and nonpharmacologic therapy use and 8% reported combined use of opioids, nonopioids, and nonpharmacologic therapy.

After adjustment for multiple factors, investigators found those who were older, had public insurance, or had more severe pain were more likely to use prescription opioids. They also reported severe pain (22%), but 4% reported only mild pain.

Study limitations included generalizability only to noninstitutionalized civilian adults, potential recall bias, and cross-sectional results that do not include patient or treatment history.

“Despite its limitations, this study identifies opportunities to improve guideline-concordant use of pharmacologic and nonpharmacologic therapies among adults with chronic pain,” the authors wrote.

There was no specific funding source for the study. The authors have reported no relevant financial disclosures.

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

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – The open-label extension trials of deuruxolitinib for alopecia areata in adults show a persistent climb in response with the majority of patients achieving complete or near complete hair regrowth by 52 weeks, according to data presented at the annual congress of the European Academy of Dermatology and Venereology.

With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.

Ted Bosworth/MDedge News

There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.

“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.

In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
 

Adverse events remained low

Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.

Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.

There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.

Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.

Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
 

Two JAK inhibitors are already approved

If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.

Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”

She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.

“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.

“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”

Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.