Chelsie Derman is an assistant editor for 

who covers psychiatry, sleep medicine, and geriatrics. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

Chelsie Derman

A study showed sedentary behavior was an independent risk factor for 

, and this association was especially pronounced in participants without hyperuricemia.

“When [physical activity] was included in our model, the association between sedentary behavior and gout remained robust, suggesting that the impact of sedentary behavior extends beyond the mere lack of [physical activity,” wrote investigators, led by Hengwei Quin, from the department of sports medicine at Huashan Hospital, Fudan University, in Shanghai, China.

On average, adults in the US spend approximately 6 hours doing sedentary activities, whether sitting, watching TV, or lying down. A study reported that sedentary time had increased from 5.5 hours per day in 2007 to 6.4 hours in 2016.

However, as extensive research has shown, a sedentary lifestyle impacts health, increasing the risk for type 2 diabetes, heart disease, depression and anxiety, cancer, and deep vein thrombosis. A study examining the association between sedentary behavior and the risk of 45 common non-communicable diseases showed that participants who reported > 6 hours of sedentary time had a greater risk of gout than participants who reported sitting ≤ 2 hours per day.

Studies have shown sedentary behavior increases the risk of hyperuricemia, but sedentary behavior’s direct connection with gout was not clear. Thus, investigators conducted a cross-sectional study to investigate the relationship between a sedentary lifestyle and gout.

The team leveraged data from the National Health and Nutrition Examination Survey database and included 34,526 participants from 2007 – 2018. Covariate data was collected for gender, age, race, education level, income-to-poverty ratio, BMI, diabetes, hypertension, chronic kidney disease, drinking status, smoking status, triglycerides, high-density lipoprotein, low-density lipoprotein, total cholesterol, serum creatinine, serum uric acid, and physical activity. Participants were excluded if they were < 20 years old, had no gout data, and had no sedentary activity data.

The sample had a mean age of 47.46 ± 17.01 years, 51.88% females, and 56.89% non-Hispanic White, followed by non-Hispanic Black, Mexican Americans, other ethnicities, and other Hispanic individuals. In total, 4.78% of participants had gout, 20.28% had hyperuricemia, and 79.72 did not have gout or hyperuricemia. Participants had an average sedentary behavior of 6.19 ± 3.39 hours per day.

Participants with gout vs no gout had many differences. For instance, participants with gout were more likely to be older, male, non-Hispanic White, obese, smokers, with hypertension, diabetes, chronic kidney disease, and hyperuricemia. Participants with gout also had lower levels of LDL, HDL, and total cholesterol, as well as greater levels of triglyceride and blood uric acid levels. These participants had less physical activity and more sedentary behavior per day.

Investigators saw a significant increase in gout prevalence from 2017 – 2018, identifying a reversed L-shaped relationship between sedentary behavior and gout (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00 – 1.06; 

The study indicates that the relationship may be mediated by body mass index (BMI), although when BMI was added to the model the association between sedentary behavior and gout lost statistical significance (

“This suggests that BMI acts as an important confounder and highlights metabolic dysregulation as a critical pathway linking sedentary behavior to gout,” investigators wrote.

Investigators noted that the link between sedentary lifestyle and gout could be due to sedentary behavior’s association with metabolic diseases. Long sedentary behavior increases lipid storage and reduces glucose intake, insulin sensitivity, muscle fiber content, and mitochondrial oxidate capacity—all of which could lead to metabolic disturbances, and later, gout.

“These findings reinforce the role of metabolic health as a mediating factor in the sedentary behavior–gout relationship,” investigators wrote.

Investigators observed this same L-shaped relationship between sedentary behavior and gout among individuals without hyperuricemia. Among participants with hyperuricemia, > 12 hours per day of sedentary behavior significantly increased the prevalence of gout.

“Our study validated the link between sedentary behavior and gout using large-scale cross-sectional data, identifying a positive correlation, and highlighting the role of hyperuricemia in this relationship, particularly in individuals with asymptomatic hyperuricemia,” investigators wrote.

Qin H, Hua Y. Association of sedentary behaviour with gout and the interaction effect of hyperuricemia: a cross-sectional study from 2007 to 2018. BMC Public Health. 2024 Dec 18;24(1):3428. doi: 10.1186/s12889-024-20937-4. PMID: 39695456.

Henson J, De Craemer M, Yates T. Sedentary behaviour and disease risk. BMC Public Health. 2023;23(1):2048.

Cao Z, Xu C, Zhang P, Wang Y. Associations of sedentary time and physical activity with adverse health conditions: outcome-wide analyses using isotemporal substitution model. EClinicalMedicine. 2022;48:101424.

Articles

Sedentary behavior is identified as an independent risk factor for gout, particularly in individuals without hyperuricemia. A cross-sectional study using data from the National Health and Nutrition Examination Survey (2007-2018) found a positive correlation between sedentary lifestyle and gout, with a reversed L-shaped relationship. The study suggests that body mass index (BMI) may mediate this relationship, highlighting metabolic dysregulation as a critical pathway. The findings emphasize the role of metabolic health in the sedentary behavior-gout link, especially in those with asymptomatic hyperuricemia.

A study found the association between sedentary behavior and gout remained strong even when adjusting for physical activity.

Sedentary Behavior Linked to Increased Gout Risk Even Without Hyperuricemia

A study showed a U-shaped association between high levels of high-density lipoprotein cholesterol (HDL-C) levels and 

, as well as between all-cause and non-cardiovascular mortality, in individuals with 

Research has previously suggested that high levels of HDL-C are protective against cardiovascular diseases, finding that each unit increase in HDL-C was linked to a decreased CVD risk by 2 – 3%.

 However, newer studies have indicated that individuals with very high HDL-C levels have an increased risk of adverse events. For instance, clinical trials with niacin and cholesteryl ester transfer protein inhibitors increased HDL-C levels but did not reduce the cardiovascular risk.

Investigators wanted to see if the relationship between HDL-C levels and the risk of major adverse cardiovascular events and mortality was present in individuals with type 2 diabetes. The primary outcome was incident major adverse cardiovascular events, and investigators examined for myocardial infarction, stroke, heart failure, and cardiovascular mortality.

“Our results suggested the need to review the role of HDL-C in the cardiovascular risk prediction in type 2 diabetes,” wrote investigators, led by David Tak Wai Lui and Lanlan Li, both from the department of medicine at the University of Hong Kong in China. “High HDL-C did not protect one from [major adverse cardiovascular events] and was even associated with worse cardiovascular outcomes.”

The retrospective cohort study included 596,943 participants with type 2 diabetes who had HDL-C records (2008 – 2020) from the electronic health record database of the Hong Kong Hospital Authority. Participants were classified based on their first-recorded HDL-C levels following diabetes diagnosis: low (≤ 40 mg/dL) (n = 168,931; 28.30%), medium (> 40 and ≤ 80 mg/dL) (n = 412,863; 69.16%), and high HDL-C (> 80 mg/dL) (n = 15,149; 2.54%).

Investigators conducted a Cox regression model analysis stratified by sex, statin use, use of anti-diabetic medications, eGFR and HbA1c levels, and obesity. During the median follow-up period of 79.5 months, or about 6 and a half years, participants with low and high-density lipoprotein cholesterol levels had a greater risk of incident major adverse cardiovascular events (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.23 – 1.26; 

 < .001) compared with participants who had medium density lipoprotein cholesterol levels (HR, 1.09; 95% CI, 1.04 – 1.13; 

“It is also interesting to note that the excess risk of [major adverse cardiovascular events] associated with high HDL-C levels was less than that associated with low HDL-C levels,” investigators wrote.

The restricted cubic spline analysis revealed a U-shaped association between HDL-C levels and incident major adverse cardiovascular events (non-linear P < .001). Investigators also observed a similar U-shaped relationship between all-cause and non-cardiovascular mortality.

The U-shape relationship was mostly consistent across subgroups, except the association did not reach statistical significance in the younger age group. The team also observed males had more exaggerated U-shaped relationships than females.

Investigators pointed out several limitations, including not having data on lifestyle factors and including a population of predominately Chinese and individuals with type 2 diabetes. They also did not have a control group of individuals without diabetes.

“In conclusion, our study demonstrated a U-shaped association between HDL-C levels and incident [major adverse cardiovascular events] in a broad spectrum of individuals with type 2 diabetes,” investigators wrote. “The results highlight the need to attend to the cardiovascular risk profile of individuals with type 2 diabetes who have high HDL-C levels, and for mechanistic studies for the increased cardiovascular risks observed at high HDL-C levels in type 2 diabetes.”

Lui DTW, Li L, Liu X, Xiong X, Tang EHM, Lee CH, Woo YC, Lang BHH, Wong CKH, Tan KCB. The association of HDL-cholesterol levels with incident major adverse cardiovascular events and mortality in 0.6 million individuals with type 2 diabetes: a population-based retrospective cohort study. BMC Med. 2024 Dec 18;22(1):586. doi: 10.1186/s12916-024-03810-4. PMID: 39696353; PMCID: PMC11657474.

Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.

Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.

Tall AR, Rader DJ. Trials and Tribulations of CETP Inhibitors. Circ Res. 2018;122(1):106–12.


A study involving 596,943 individuals with type 2 diabetes revealed a U-shaped association between high-density lipoprotein cholesterol (HDL-C) levels and major adverse cardiovascular events, as well as all-cause and non-cardiovascular mortality. While traditionally considered protective, very high HDL-C levels were linked to increased cardiovascular risks. The study highlighted the need to reassess HDL-C's role in cardiovascular risk prediction for type 2 diabetes patients. Limitations included a lack of lifestyle data and a predominantly Chinese cohort. The findings suggest further investigation into the mechanisms behind these risks is necessary.

A study finds that individuals with low or high LDL cholesterol levels face a greater cardiovascular risk than those with medium levels.

Study Shows a U-Shaped Association Between HDL-C, Major Adverse Cardiovascular Events

A phase 3 trial demonstrated that taking brexpiprazole alongside sertraline significantly reduced overall PTSD symptoms in 10 days compared with sertraline plus placebo.

Otsuka Pharmaceutical and Lundbeck announced on December 18, 2024, that the full results of their phase 3 trial were published in JAMA Psychiatry.

“About 6% of the United States population will have PTSD at some point in their lives, but around only half will seek treatment,” said lead investigator Lori Davis, MD, clinical professor of psychiatry at the University of Alabama School of Medicine.

 “The Phase 3 results are an important and encouraging step forward in the hopes of providing PTSD patients with a new therapeutic option in the future.”

The publication of this data follows Otsuka and Lundbeck’s announcement on June 25, 2024, that the US Food and Drug Administration (FDA) accepted the supplemental New Drug Application (sNDA) filing for brexpiprazole in combination with sertraline for the treatment of adults with PTSD.

 The FDA assigned the sNDA a Prescription Drug User Fee Act (PDUFA) target action date of February 8, 2025.

The recently published data was a phase 3 randomized, double-blind, active-controlled, parallel-arm trial conducted from October 2019 to August 2024.

 Investigators evaluated the efficacy, safety, and tolerability of brexpiprazole plus sertraline in 416 adult patients aged 18 – 65 years (mean age: 37.4 years; 74.5% female) with PTSD.1 The sample was mostly White (70%), followed by 21.2% Black or African American, 14.7% Hispanic or Latino, 3.1% Asian, 2.2% American Indian or Alaska Native, and 0.2% Native Hawaiian or other Pacific Islander.

Participants were randomized to receive either brexpiprazole (2 – 3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with a placebo. The primary endpoint was the change in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10.

The trial began with a 1-week placebo period followed by an 11-week double-blind, randomized, active-controlled, parallel-arm period and then a 21-day follow-up. The study had taken place at 86 clinical trial sites in the US.

Participants on brexpiprazole with sertraline experienced a statistically significant greater improvement in the CAPS-5 total score (-19.2) compared with those receiving sertraline with placebo (-13.6) (least squares mean difference, -5.59; 95% confidence interval [CI], -8.79 to -2.28; P < .001) by week 10. The study also met both secondary endpoints: change in the Clinical Global Impression-Severity of Illness score (CGI-S) from week 1 to 10 and Brief Inventory of Psychological Function (B-IPF) from week 0 to 12.

Brexpiprazole with sertraline showed a comparable safety profile to brexpiprazole in approved indications. Already approved indications include adjunctive therapy to antidepressants in adults with major depressive disorder and schizophrenia and the treatment of agitation linked to dementia due to Alzheimer Disease.2

A greater percentage of participants on placebo + sertraline discontinued due to adverse events (10.2%) compared to participants on brexpiprazole + sertraline (3.9%). However, more participants on brexpiprazole + sertraline experienced adverse events than those on placebo + sertraline, and common adverse events (incidence of ≥ 5%) included nausea (12.2% vs 11.7%), fatigue (6.8% vs 4.1%), weight gain (5.9% vs 1.5%), and somnolence (5.4% vs 2.6%, respectively.

“The outcome of this trial provides us with an opportunity to help patients with PTSD,” said Johan Luthman, executive vice president and head of Research & Development at Lundbeck, in a statement. “With these promising results, we are committed to working closely with the FDA to help bring brexpiprazole in combination with sertraline to the healthcare professionals serving the PTSD patient community.”

Davis LL, Behl S, Lee D, et al. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. 

 Published online December 18, 2024. doi:10.1001/jamapsychiatry.2024.3996

JAMA Psychiatry Publishes Results of Otsuka and Lundbeck's Phase 3 Trial of Brexpiprazole in Combination with Sertraline in Treatment of Post-Traumatic Stress Disorder (PTSD) in Adults. Otsuka. December 18, 2024. 

https://www.otsuka-us.com/news/jama-psychiatry-publishes-results-otsuka-and-lundbecks-phase-3-trial-brexpiprazole-combination

Derman, C. FDA Accepts sNDA for Brexpiprazole in Combination with Sertraline for Adult PTSD. HCPLive. June 25, 2024. 

https://www.hcplive.com/view/fda-accepts-snda-for-brexpiprazole-in-combination-with-sertraline-for-adult-ptsd

A phase 3 trial revealed that brexpiprazole combined with sertraline significantly reduced PTSD symptoms compared to sertraline with placebo. Conducted from 2019 to 2024, the trial involved 416 adults and demonstrated a greater improvement in CAPS-5 scores for the brexpiprazole group. The combination also met secondary endpoints and showed a safety profile consistent with brexpiprazole's approved uses. Despite more adverse events in the brexpiprazole group, fewer participants discontinued due to adverse events. The FDA is reviewing the combination for PTSD treatment, with a decision expected in February 2025.

A phase 3 trial shows promising data for brexpiprazole with sertraline for PTSD symptoms ahead of the supplemental new drug application’s PDUFA date in February 2024.

Brexpiprazole with Sertraline Significantly Reduces PTSD Symptoms in 10 Days

A study showed tralokinumab is an effective treatment for moderate-to-severe 

in adult patients who are both dupilumab-naïve and dupilumab non-naïve.

“This prospective multicenter study provides insight into the daily practice effectiveness and safety of the first 28 weeks of treatment with tralokinumab in adult [atopic dermatitis] patients,” wrote investigators, led by Coco Dekkers, PhD candidate, from University Medical Center Utrecht in the Netherlands.

Tralokinumab, a biological that targets interleukin-13, is a relatively new advanced systemic treatment for patients with moderate-to-severe atopic dermatitis.

 Phase 3 trials demonstrated the efficacy and safety of this drug, but more daily practice data was needed.

Investigators sought to evaluate the 28-week safety and effectiveness of tralokinumab in daily practice, as well as serum proteins and total IgE levels, in patients with atopic dermatitis.

 The team collected data from patients from the BioDay registry, including a total of 84 patients with 39 dupilumab-naïve and 45 who had previously failed dupilumab treatment. The sample had a mean age of 42.5 years with 48.8% male.

Among the sample, 8 patients (9.5%) were actively treated with concomitant systemic immunosuppressive treatments, often cyclosporine, and 32 patients (38.1%) were in the washout of previous systemic immunosuppressive treatment. The sample included 26.2% patients who started tralokinumab during the washout period of dupilumab.

The primary endpoints were the absolute values of the Eczema Area and Severity Index (EASI) (range: 0 – 72), Numeric Rating Scale for pruritus (0 – 10), Numeric Rating Scale for pain, Dermatology Life Quality Index (0 – 30), and Patient-Oriented Eczema Measure (0 – 28) after 4, 16, and 28 weeks of treatment with tralokinumab. Investigators chose to examine absolute values over relative values since earlier systemic therapies did influence data after weeks 16 and 28. Secondary endpoints included absolute cutoff scores of EASI ≤ 7, IGA ≤ 1, and Numeric Rating Scale for pruritus ≤ 4 after 4, 16, and 28 weeks of treatment.

At baseline, participants had a mean EASI of 11.0; the average for dupilumab-naïve and non-naïve patients was 12.2 and 9.8, respectively. Additionally, patients exposed to dupilumab (62.2%) had a greater recorded use of concomitant immunosuppressive treatment than dupilumab-naïve patients (30.8%). The IGA significantly differed among patients who were and were not naïve to dupilumab, with moderate-to-severe disease found in most dupilumab-naïve patients and mild-to-moderate disease found in non-naïve patients.

The study showed all primary outcomes significantly improved during the follow-up period. By week 28, the mean EASI reduced from 11.0 (95% confidence interval [CI], 9.1 – 12.8) to 4.9 (95% CI, 4.0 – 5.8), and the Numeric Rating Scale for pruritus reduced from 6.1 (95% CI, 5.5 – 6.7) to 4.6 (95% CI, 4.0 – 5.2).

Despite finding the change in EASI and Numeric Rating Scale for pruritus significantly differed between dupilumab-naïve and dupilumab non-naïve patients during treatment, the groups had small absolute differences after 28 weeks (EASI: 4.7 vs 5.3; Numeric Rating Scale for pruritus: 4.3 vs 4.8, respectively).

Investigators observed a similar trend when comparing patients with complete washout (n = 44) vs without complete washout (n = 40) of other immunosuppressive therapies at the beginning of tralokinumab treatment. Patients without complete washout had a lower EASI at baseline and a lower percentage of improvement in EASI from baseline compared with patients with a complete washout.

The study discovered the probability of achieving EASI ≤ 7, Numeric Rating Scale for pruritus ≤ 4, and IGA ≤ 1 after 28 weeks of treatment was 75.8%. Participants who were dupilumab-naïve vs non-naïve had a greater likelihood of achieving these endpoints.

Patients (n = 46) reported 62 adverse events during 28 weeks of treatment. Most adverse events were mild (58.1%), and common ones included eye disorders (28.6%), general disorders such as malaise (9.5%), nervous system disorders such as headaches (9.5%), and skin and subcutaneous disorders such as hair loss (9.5%).

In total, 13 patients (15.5%) discontinued treatment following an adverse event. All 6 patients who experienced hair loss discontinued the treatment. Other adverse events leading to discontinuation included conjunctivitis (n = 5), headache (n = 1), and rosacea (n = 1).

Among 10 patients who were previously treated with dupilumab an average of 20 weeks before starting tralokinumab treatment, the serum concentration of dupilumab after the 10-week washout period reached maximum values of 0.052 mg/L. Moreover, the median serum IgE level significantly decreased on average from 1096.0 to 671.0 in dupilumab-naïve patients and 360.0 to 331.0 in dupilumab non-naïve patients after 28 weeks of treatment from baseline.

“Despite acting on the same immunologic pathway, our study indicates that considering tralokinumab after dupilumab discontinuation is a valuable option,” investigators concluded.

Dekkers C, Zuithoff N, Bakker D, Knol E, Wevers A, Touwslager W, Christoffers W, Prosje P, van Lynden-van Nes A, van Lümig P, Kamsteeg M, Oosting AJ, Schuttelaar MLA, Haeck I, de Graaf M, van Wijk F, de Bruin-Weller M. Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28-Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels. Allergy. 2024 Dec 14. doi: 10.1111/all.16414. Epub ahead of print. PMID: 39673366.

Blair HA. Tralokinumab in Atopic Dermatitis: A Profile of Its Use. Clin Drug Investig. 2022 Apr;42(4):365-374. doi: 10.1007/s40261-022-01135-9. Epub 2022 Mar 22. PMID: 35316850.

Tralokinumab has demonstrated effectiveness in treating moderate-to-severe atopic dermatitis in both dupilumab-naïve and non-naïve adult patients over a 28-week period. The study, involving 84 patients, showed significant improvements in primary outcomes such as EASI and pruritus scores. While adverse events were reported, most were mild, with some leading to treatment discontinuation. The study suggests tralokinumab as a viable option post-dupilumab discontinuation, despite both targeting the same immunologic pathway. Serum IgE levels decreased significantly, particularly in dupilumab-naïve patients.

In a recent study, tralokinumab demonstrates effectiveness and safety for treating moderate-to-severe atopic dermatitis in adults who are dupilumab naïve and non-naïve.