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experience abrupt transitions between neutral and negative emotional states, with the magnitude of this shift escalating depending on the severity of the emotional numbing symptoms, a new study found.

“These preliminary results provide valuable insights into the complex association between emotional processing and PTSD symptoms,” wrote investigators, led by Nachshon Korem, PhD, from the department of psychiatry at Yale University School of Medicine.

PTSD is characterized as experiencing contrasting symptoms of hyperemotional reactivity (neutral state) and emotional numbing (negative state). Although emotional numbing is considered to restrict positive emotions, it is also suggested to limit negative emotions, too.

 Alongside emotional numbing, many symptoms of PTSD are associated with hyperactivity to emotional stimuli.

In their cross-sectional study, investigators sought to explore whether individuals grappling with PTSD encountered a significant shift from neutral to negative emotional states and how the emotional numbing severity influences the transition.

From January 17 to March 8, 2023, the team recruited trauma-exposed individuals who either witnessed or experienced a life-threatening incident, violent assault, or someone being killed. Participants completed the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). They were considered to have PTSD if they had a PCL-5 score of ≥ 33 and had ≥ 1 intrusion symptom, 1 avoidance symptom, 2 negative alterations in cognition and mood symptoms, and 2 alterations in arousal and reactivity symptoms.

The study included 1440 trauma-exposed individuals who either were probable PTSD (n = 445) or trauma-exposed controls. The PTSD group leaned younger with a mean age of 36.1 years than the controls with a mean age of 41.5 years (

The sample was made up of mostly White participants (75.3%, followed by African American or Black (7.4%), Multiracial (5.5%), Asian (4.6%), other race (1.6%), preferred not to say (0.7%), and American Indian or Alaska Native (0.6 %). The study included 47.6% of females, and the groups had similar sex distributions, with 230 women in the PTSD group and 427 in the control group (

Investigators analyzed PTSD emotions using hierarchical Bayesian modeling in the logistic regression to analyze the valence ratings of 40 images. The images included stimuli, featuring faces, people, and animals. The team aimed to compare the curve’s slope between groups and explore the association between the slope and the severity of emotional numbing symptoms.

The primary outcome was the slope parameter derived from the logistic curve fitted to the valence rating. The slope parameter represented the rate at which emotional response intensity alters with stimulus valence, indicating the transition speed between neutral and negative valence states.

Overall, the PTSD group demonstrated a steeper slope than the controls (mean slope difference, -0.255; 89% highest posterior density [HPD], -0.340 to -0.171), indicating a sharper transition. Investigators observed a strong association between the slope and emotional numbing severity (mean additive value, 0.100; 89% HPD, 0.051 – 0.15). After controlling for age, emotional numbing was still associated with transition sharpness (additive value, 0.108; 89% HPD, 0.056 – 0.159) without an age-related association (additive value, 0.031; 89% HPD, -0.022 to 0.083).

The team outlined several limitations including potential data manipulation of lower data quality due to using online studies, the age differences between the 2 groups, not collecting data on index trauma, trauma load, childhood trauma, and time since trauma, and using non-trauma-specific images.

“This study advances our understanding of emotional processing in PTSD by focusing on the transitional dynamics between neutral and negative emotional states, a facet often overlooked in traditional research,” investigators concluded. “These transitional dynamics’ robust association with the severity of emotional numbing symptoms extends the prevailing understanding of emotional experiences in PTSD beyond intensity metrics. The steeper slope in emotional transitions holds notable clinical implications, directing attention toward developing targeted interventions that focus on emotion regulation.”

Korem, N, Duek, O, Spiller, T. Emotional State Transitions in Trauma-Exposed Individuals With and Without Posttraumatic Stress Disorder. 

 2024;7(4):e246813. doi:10.1001/jamanetworkopen.2024.6813 (Reprinted)

https://www.ptsduk.org/emotional-numbness/

Articles

A new study found individuals with PTSD face rapid transitions between neutral and negative emotional states.

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PTSD Emotional Numbing Impacts Intensity of Neutral to Negative State Shifts

Experts discuss the practice of loading doses for newer agents and when they would consider this suitable for patients.

Perspectives on Loading Dose Recommendations for New Therapies

In this segment, the experts discuss the practice of loading doses when switching patients to aflibercept 8 mg. David Eichenbaum, MD inquires whether the experts recommend loading when transitioning patients, especially those who are already on a different treatment cadence. Kenny Fan, MD expresses hesitation in convincing patients to undergo loading when switching from a less frequent dosing schedule to aflibercept 8 mg. He highlights the challenge of persuading patients to undergo a more intensive treatment schedule, especially if they are already satisfied with their current regimen. Seenu Hariprasad, MD suggests that the decision to load depends on the specific scenario. For patients who have been on a stable regimen for an extended period, he may not opt for loading. However, for those with persistent disease activity, he considers taking advantage of loading doses for a more aggressive approach. Diana Do, MD notes that she typically reserves loading for treatment-naive patients. However, if there is substantial disease activity, she supports being aggressive with loading doses to provide patients with the best chance for vision improvement.

This summary was AI-generated and edited for clarity.

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Abigail Brooks is an assistant editor for 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Barratt discusses subgroup analyses of the phase 3 PROTECT trial and what they add to previous findings about the use of sparsentan versus irbesartan in IgAN.

Jonathan Barratt, MD: Sparsentan’s Benefit Across Baseline Proteinuria Groups in PROTECT

Subgroup analyses of the phase 3 PROTECT trial highlight sparsentan’s clinically meaningful benefit over irbesartan for long-term kidney preservation, absolute change in estimated glomerular filtration rate (eGFR), and rate of eGFR change in adult patients with primary 

 across baseline proteinuria subgroups over 2 years.

Findings were presented at the World Congress of Nephrology in Buenos Aires, Argentina, on April 15, 2024, complementing initial 2-year findings presented last year in a late-breaking oral presentation at the American Society of Nephrology Kidney Week 2023, which provided evidence suggesting use of sparsentan was associated with a more significant antiproteinuric effect at 110 weeks, confirmed by chronic and total eGFR slope, relative to use of irbesartan in patients with IgAN.

“The data is very much more looking at subgroup analyses. It doesn't detract. In fact, it reinforces the value of sparsentan with dual ARB ERA blockade in managing IgA nephropathy, so it's supportive data,” Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, said in an interview with HCPLive. “We've had the headline data already, so it's not going to change that in any way.”

A dual endothelin type A and angiotensin II type 1 receptor antagonist, sparsentan received accelerated approval for reducing proteinuria in adults with primary IgAN in February 2023, making it the first and only non-immunosuppressive treatment targeting glomerular injury in the kidney to reduce proteinuria in this patient population at risk of rapid disease progression. On March 11, 2024, Travere Therapeutics submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for conversion of the existing accelerated approval to full approval, based on 2-year confirmatory results from PROTECT in which sparsentan demonstrated long-term kidney function preservation and achieved a significant reduction in proteinuria and a clinically meaningful difference in eGFR slope versus an active comparator, irbesartan.

“The bottom line is, if we're talking about sparsentan and irbesartan, they are completely complimentary and they do completely different things. In where we are heading in terms of IgA therapeutics, those are drugs I would be wanting to think about using together alongside a drug that targets pathogenic IgA production,” Barratt explained.

Findings presented at the World Congress of Nephrology showed sparsentan outperformed irbesartan for complete proteinuria remission, defined as urine protein excretion < 0.3 g/day, (31% vs 11%; RR, 2.5; 95% CI, 1.6 to 4.1), as well as for change in eGFR mL/min/1.73m2 (-5.8 vs -9.5; 95% CI, 1.5 to 6.0). Results also showed sparsentan (17.4 years) had a greater potential long–term impact of improved eGFR slope on time to dialysis, besting both irbesartan (12.4 years) and renin-angiotensin system inhibitor standard of care (8.9 years).

Serious treatment-emergent adverse events were comparable between the groups (37% vs 35%), with no drug-induced liver injury in the sparsentan group. Additional subgroup analyses by urine protein-to-creatinine ratio revealed sparsentan was favored across all subgroups for absolute change in eGFR by baseline proteinuria.

Barratt J, et al. Sparsentan vs Irbesartan in Patients with IgAN: Subgroup Analyses of 2-Year Results from the Pivotal Phase 3 PROTECT Trial. Presented at: World Congress of Nephrology (WCN) 2024 Annual Scientific Session. April 13 – 16, 2024. Buenos Aires, Argentina.

Campbell P. PROTECT: Sparsentan Outperforms Irbesartan in IgA Nephropathy 

. November 3, 2023. Accessed April 16, 2024. 

https://www.hcplive.com/view/protect-sparsentan-outperforms-irbesartan-in-iga-nephropathy

Travere Therapuetics. Travere Therapeutics Submits Supplemental New Drug Application to the U.S. Food and Drug Administration Seeking Full Approval of FILSPARI® (sparsentan) for the Treatment of IgA Nephropathy (IgAN). March 11, 2024. Accessed April 16, 2023. 

https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-submits-supplemental-new-drug-application

Barratt discusses results from subgroup analyses of the phase 3 PROTECT trial based on baseline proteinuria and what they add to previous findings.

Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

IgA Nephropathy

The HCPLive Berger disease page is a resource for medical news and expert insights on IgA nephropathy. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in Berger disease, and more.

Jonathan Barratt, MD: PROTECT Subgroup Analyses Continue to Favor Sparsentan for IgAN

Patrick Campbell is the managing editor of HCPLive. Formerly the editorial lead of Endocrinology Network, Practical Cardiology, and Rheumatology Network, Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. He now helps to lead coverage in each of these respective areas for HCPLive. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

An analysis of data from the National Inpatient Sample over 15 years details the impact of the 2013 publication of the TTM trial on use of targeted temperature management (TTM) in the US.

American College of Cardiology 2024 (ACC.24) Annual Scientific Session

, results of the analysis suggest use of TTM in out-of-hospital cardiac arrest survivors increased steadily from 2005 through 2013, but saw a decline each year after, which investigators worry may represent a misinterpretation of study findings.

An international, multicenter, randomized trial, the TTM trial, which was published in the 

, randomized 950 unconscious adults with out-of-hospital cardiac arrest of presumed cardiac cause in a 1:1 ratio to targeted temperature management at either 33°C or 36°C. The trial’s primary outcome of interest was all-cause mortality through the end of the trial, which had a mean follow-up of 256 days.

Results of the trial indicated all-cause mortality occurred among 50% of the 33°C group and 48% of the patients in the 36°C group (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; 

= .51). Secondary analyses in the trial concluded 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; 

In the ACC.24 presentation, investigators sought to describe trends in TTM use and predictors in the US before and after the publication of the TTM trial. With this in mind, investigators designed their study as an analysis of data from the National Inpatient Sample. Using 2005 through 2020 as the period of interest, investigators identified 2,803,130 admissions, including 53,858 (1.92%) who received TTM.

Upon analysis, results indicated TTM use was lowest in 2005, when rates reached 0.45%, and peaked at 3.44% in 2013 (

 <.001). However, a subsequent decline was observed following this point (Trend: -0.27%; 

 <.001). Analysis of predictors suggested Black and Hispanic patients were less likely to receive TTM than White patients (OR, 0.87 and 0.64; 

 <.001). Investigators also pointed out those receiving care at urban teaching and non-teaching hospitals (OR, 1.98 and 1.91; 

 <.001) had greater likelihood of receiving TTM.

For more on the study and trends in TTM use in the US, check out our interview with study investigator José López, MD, cardiology fellow at the University of Miami JFK Medical Center, from the conference floor at ACC.24.

HCPLive: Can you describe the impetus behind this analysis?

So, I got the idea with the first author, Dr. Justin Mark. We came up with this idea because around the publication of the TTM trial, there was a lot of talk and controversy about whether TTM was useful or not. Many doctors, even at my hospital, were discussing how they didn't want to use TTM anymore because they believed it didn't work. However, as I was diving deeper into the topic and read through all the trials, I realized there might have been a misinterpretation of the data. That's when the idea hit me—let's see if we can correlate the utilization of TTM with the publication of these trials and examine it over a broad timeline. That's why we looked at TTM utilization from 2005 to 2020, and we found some really interesting findings.

HCPLive: What were the results and why are they important?

We essentially utilized the National Inpatient Sample and examined patients with any type of cardiac arrest admitted to the hospital between 2005 and 2020. Our focus was on the utilization of TTM. We discovered that out of more than 2.8 million post-cardiac arrest patients during this period, only 1.92% received TTM, totaling about 53,850. This low utilization rate indicates that the therapy is underutilized, considering it is indicated for more patients.

The second significant finding was that TTM utilization was increasing until 2013, after which it sharply declined. This decline can be correlated with the publication of different trials. For instance, the HACAT and Bernard trials published in 2000 demonstrated that TTM, cooling to target temperatures of 33 to 36 degrees Celsius, was superior to maintaining a temperature of 37 degrees Celsius in improving neurological outcomes in patients with shockable rhythm.

However, when the TTM trial was published in 2013, the same year, utilization started to decline. This trial showed no difference in mortality or neurological deficits. Yet, I believe a few crucial aspects of the study were overlooked. First, the TTM trial lacked a comparison arm, comparing only 33 degrees to 36 degrees without comparing to normothermia. Second, patients in that trial had a longer time to resuscitation, which suggests a higher degree of neurological injury. These trials are important, but I believe they may have been misinterpreted, leading to decreased utilization of this therapy, despite its significant role in select patient populations.

Mark J, Lopez J, Colombo R, et al. TEMPORAL TRENDS AND PREDICTORS OF TARGETED TEMPERATURE MANAGEMENT IMPLEMENTATION FOR CARDIAC ARREST SURVIVORS. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.

Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. 

. 2013;369(23):2197-2206. doi:10.1056/NEJMoa1310519

An ACC.24 analysis found a decline in TTM use post-2013 TTM trial, which investigators suggest indicates a potential misinterpretation of trial findings.

Cardiology

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Trends in Targeted Temperature Management Before and After 2013, with José López, MD

Experts discuss the importance of fluid management, presenting a range of perspectives on managing complex cases.

Perspectives on Retinal Fluid Management

In this segment, the discussion centers around the concept of complete fluid resolution and its significance. David Eichenbaum, MD raises the question to David Brown, MD asking whether patients who have met the extension criteria and achieved complete fluid resolution at 20 or 24 weeks are genuinely benefiting from the drug by that point. David Brown responds by referring to prior studies that had strict criteria for treatment. He notes that around 15 to 20% of patients met the criteria after three doses and were done with treatment. He emphasizes the importance of understanding how many patients, especially at the 20 or 24-week mark, are truly completely dry. He continues, expressing his preference for having criteria similar to aflibercept 8 milligrams and reports, which would provide information on how many patients achieved complete fluid resolution at extended intervals. He underscores the need for accurate data to distinguish between patients who may not need further treatment and those who would benefit from ongoing therapy based on fluid status.

Experts discuss the importance of fluid management, presenting a range of perspectives on managing complex cases. 

Ophthalmology

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Connor Iapoce is an associate editor for 

 and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at 

A proactive treat-and-extend protocol yields superior results with fewer visits than a less intensive regimen in the first year of treatment for DME.

Diabetic Macular Edema

The HCPLive diabetic macular edema page is a comprehensive resource for clinical news and insights on DME. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for the leading cause of blindness, and more.

Treat-and-Extend Regimen Superior in First Year of DME Treatment

Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

In this analysis, the study investigators highlighted the impact of smoking cigarettes on PASI 75 achievement.


Plaque Psoriasis

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Psoriasis Severity Index Scores Impacted by Tobacco Smoking in Current, Former Smokers

A new study explored increased health care utilization of children among several specific sleep disorders, race, and age.

Sleep

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Children with Sleep Disorders Have Double the Odds of Increased Health Care Usage

Lana Pine is the editor of HCPLive Rheumatology. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. In her free time, she enjoys cooking, yoga, listening to podcasts, and drawing. She can be reached via email at LPine@mjhlifesciences.com.

EULAR’s fibromyalgia guidelines provide comprehensive recommendations for managing active fibromyalgia to assist clinicians in making informed decisions. Test your knowledge with this quiz.

Fibromyalgia

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Clinical Quiz: EULAR Guidelines for the Treatment of Fibromyalgia 

Counting down the most impactful news at major medical meetings, it’s the HCPLive Five! This edition focuses on 5 updates from the American College of Cardiology 2024 (ACC.24) Annual Scientific Sessions.

HCPLive Five at ACC 2024

Barratt discusses the potential of targeting the alternative pathway for controlling inflammation and the significance of the new APPLAUSE-IgAN data.

Jonathan Barratt, MD: Targeting the Alternative Complement Pathway in IgAN with Iptacopan

S Louis Bridges Jr, MD, PhD, explores the role of artificial intelligence in managing rheumatoid arthritis. 

Rheumatoid Arthritis

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S Louis Bridges Jr, MD, PhD: Integrating AI into RA Management

A recent multi-center study identified risk factors linked to premature mortality in sickle cell disease, including male gender and hematologic and biochemical parameters.

Hematology

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Patients with SCD Face Early Death Despite Improved Survival Rates 

Laura Ross, PA-C, sits down for a Q&A on the HeartBeet Clinic and the role of reimbursable group visits in cardiovascular disease management and education. 

Dyslipidemia

Laura Ross, PA-C: HeartBeet Clinic Offers Efficient, Reimbursable Avenue for Improving CV Risk Factors

This post-hoc analysis of phase 3 data, using GRAPPA-recognized PsA domains, highlighted disease improvements following treatment with guselkumab.


Psoriatic Arthritis

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Latest News

PTSD Emotional Numbing Impacts Intensity of Neutral to Negative State Shifts

Perspectives on Loading Dose Recommendations for New Therapies

Jonathan Barratt, MD: PROTECT Subgroup Analyses Continue to Favor Sparsentan for IgAN

Trends in Targeted Temperature Management Before and After 2013, with José López, MD

Perspectives on Retinal Fluid Management