Severe Symptoms Research Articles

Recent Vaccination Against SARS-CoV-2 Is Associated with Less Severe Disease in Working-Age Adults

Background: Essential workers, including those working in healthcare and education, are at higher risk of exposure to communicable diseases, including SARS-CoV-2. Reducing the rates of infection is important for their personal health and for the ongoing safe operation of essential services. Methods: Data from participants in two prospective cohort studies who tested positive for SARS-CoV-2 in 2020 through 2023 were used to determine whether vaccination against SARS-CoV-2 is associated with the severity of symptoms in working-age adults. Results: SARS-CoV-2-positive tests (N = 3757) were reported by 3093 participants (mean: 1.2 per person); 1229 (33%) illnesses did not interfere with regular activities, 1926 (51%) made participants too unwell for regular activities, and 602 (16%) required participant bed rest. Compared with vaccine receipt more than 12 months earlier, receipt within six months of an infection was associated with lower risk ratios for more severe illness (too unwell: 0.69 and bed rest: 0.67) compared with being able to conduct regular activities. More recent vaccination was also associated with lower odds reporting of systemic symptoms (fever, myalgia, arthralgia) and fewer solicited symptoms. Conclusion: Staying current with COVID-19 vaccinations should continue to be recommended since receiving a recent immunization lessened the severity of illness. Also, as symptoms of COVID-19 are now largely similar to other respiratory viruses, practitioners need to use this evidence to inform diagnostic testing and return-to-work policies.

Characteristic of mental health app usage: a cross-sectional survey in the general population.

Mental health apps (MHA) have gained popularity in recent years. Most freely available apps are of low quality and lack evidence for effectiveness. Yet, download rates indicate high usage. MHA are potentially beneficial for individuals with no/low symptom severity as prevention, or as an option to reach underserviced populations. However, currently very little is known about the characteristics of MHA users in the general population, about the kind of MHA used, or the motivation behind MHA usage. We collected survey-data from N = 1,247 individuals from the general population to investigate MHA usage. Descriptive statistics revealed that 41% had used MHA in the past 12 months; prescription app-use however was low (1.5% of MHA users). Mindfulness, moodtracking, and relaxation were the most popular categories of MHA. Perceived helpfulness, fun, and availability were the top reasons for MHA usage. Non-users reported distrust, lack of perceived need, and data security concerns as usage barriers. MHA users and non-users did not differ regarding sociodemographic variables. Multiple regression analyses revealed that sub-threshold symptoms of psychological disorders as well as higher levels of anxiety and stress were linked to higher probability of MHA usage. Higher levels of depression were associated with lower likelihood of MHA usage in general, but increased likelihood of usage of self-help apps specifically for depression. It follows that MHA use is common in the general population independent of sociodemographic characteristics. MHA can reach people who might benefit, but more awareness and better structure of the market is needed to reduce distrust, increase usage of high-quality MHA, and improve the fit between app and user.

The voice of depression: speech features as biomarkers for major depressive disorder.

Psychiatry faces a challenge due to the lack of objective biomarkers, as current assessments are based on subjective evaluations. Automated speech analysis shows promise in detecting symptom severity in depressed patients. This project aimed to identify discriminating speech features between patients with major depressive disorder (MDD) and healthy controls (HCs) by examining associations with symptom severity measures. Forty-four MDD patients from the Psychiatry Department, University Hospital Aachen, Germany and fifty-two HCs were recruited. Participants described positive and negative life events, which were recorded for analysis. The Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression gauged depression severity. Transcribed audio recordings underwent feature extraction, including acoustics, speech rate, and content. Machine learning models including speech features and neuropsychological assessments, were used to differentiate between the MDD patients and HCs. Acoustic variables such as pitch and loudness differed significantly between the MDD patients and HCs (effect sizes 𝜼2 between 0.183 and 0.3, p < 0.001). Furthermore, variables pertaining to temporality, lexical richness, and speech sentiment displayed moderate to high effect sizes (𝜼2 between 0.062 and 0.143, p < 0.02). A support vector machine (SVM) model based on 10 acoustic features showed a high performance (AUC = 0.93) in differentiating between HCs and patients with MDD, comparable to an SVM based on the BDI-II (AUC = 0.99, p = 0.01). This study identified robust speech features associated with MDD. A machine learning model based on speech features yielded similar results to an established pen-and-paper depression assessment. In the future, these findings may shape voice-based biomarkers, enhancing clinical diagnosis and MDD monitoring.

Abstract 4127909: Smartphone-enabled, home-based exercise in patients with symptomatic peripheral arterial disease: the Smart Step Grady randomized trial

Introduction: About 10% of peripheral artery disease (PAD) patients develop claudication, with African Americans at higher risk and more severe symptoms. While supervised exercise therapy (SET) is a primary treatment, its uptake is low. We assessed the feasibility and effectiveness of smartphone-delivered home-based exercise therapy (HBET) in improving functional capacity and PAD symptoms in low-resource settings lacking SET. Methods: We conducted an interim analysis of Smart Step, a pilot randomized trial (1:1 ratio) comparing smartphone-enabled HBET to usual care (UC) in symptomatic PAD patients at Grady Memorial Hospital, a public safety net hospital in Atlanta, GA, from August 2018 to March 2024. The HBET group received virtual exercise coaching, app-based education, messaging, and reminders for 12 weeks. The primary outcome was the change in 6-minute walking distance (6MWD) at 12 weeks. Secondary outcomes included changes in the Walking Impairment Questionnaire (WIQ) and Short Form 36 (SF-36) scores. Data were analyzed using intention-to-treat, with mixed model repeated measures regression assessing the association between 6MWD and treatment. Results: We screened 102 patients and enrolled 46. To date, 26 (56%) participants have completed the study, 6 (13%) dropped out, and 14 (30%) are pending completion. The mean [SD] age was 63 [12] years, with 50% female and 90% African American. After 12 weeks, the mean 6MWD increased by 15.7 m from a baseline of 336.0 m in the HBET arm (n=13) and decreased by 6.6 from a baseline of 310.2 m in the UC arm (n=13). The between-group difference was 22.4 [95% CI -11.8 – 56.6] m; p=0.19). The WIQ stair climbing score changed by -10.9 in the UC arm vs. 7.1 in the HBET arm (between group difference 17.9 [95% CI 1.1-34.8]; p=0.04), while the other WIQ sub-scores were more similar between groups. The 12-week changes in SF-36 scores were not different by group. Conclusion: In this preliminary analysis, the HBET arm showed within-group improvements in 6MWD and symptoms after 12 weeks, but most changes were not significantly different when comparing them with the UC arm. Future analyses are pending and will provide the necessary statistical power for a more precise measure of the treatment effects.

Abstract 4122120: Prospective Implementation of a Cardiovascular Implantable Electronic Device Algorithm-Based Management Pathway in Routine Heart Failure Care

Introduction: More than 1 million patients in the US are hospitalized annually with heart failure (HF), many of whom have cardiovascular implantable electronic devices (CIEDs). CIEDs monitor physiologic variables that could identify subacute HF decompensation and impending HF hospitalization (HFH). One such algorithm is Medtronic’s TriageHF TM , which integrates nine diagnostic inputs from remote monitoring data to stratify patients into categories of low-, medium-, or high-risk of HFH in the next 30 days. Goals/Aims: To implement and evaluate a program in which two Veterans Health Administration (VHA) cardiology clinics receive high-risk TriageHF TM scores for patients with CIEDs, followed by contacting and assessing patients and then taking appropriate clinical action. Methods: From 1/18/24 to 4/19/24, TriageHF TM risk scores were calculated from both HF-specific remote transmissions that were scheduled every 30 days and unscheduled remote transmissions. Clinicians then contacted patients with high-risk scores regarding possible symptoms and provided an empiric 3-day diuretic intervention (initiation or dose augmentation), adjusted guideline-directed medical therapy (GDMT), or performed another clinical action as appropriate. Results: Among 358 patients with 1140 transmissions, 72 (6%) patients had a high-risk transmission. Mean patient age was 72.8 years, 346 (97%) were male, and 221 (62%) had a pre-existing diagnosis of heart failure. Of the 72 patients with high-risk transmissions, 67 (93%) were successfully contacted; 34 (51%) had no HF symptoms, 24 (36%) had mild to moderate symptoms, 2 (3%) had severe symptoms, 4 (6%) had non-HF symptoms, and 3 (4%) could not report symptoms. Of the 67, 57 (85%) reported adherence to medications and 17 (25%) were identified as likely having a non-HF related high-risk score. Forty-six (69%) had a clinical action taken in response to the high-risk score, including 28 (42%) with a diuretic intervention, 12 (18%) with GDMT augmented, and 25 (37%) with other actions, such as being referred to HF clinic. Conclusions: In this implementation study, clinicians contacted and assessed nearly all patients at high-risk for HF decompensation based on CIED remote monitoring data. Approximately 70% of patients had an actionable high-risk score, with approximately half prescribed empiric diuretics or augmented GDMT. A randomized clinical trial is needed to determine whether this algorithm and subsequent intervention improves clinical outcomes.

Abstract 4119680: First-in-Man Treatment of Heart Failure by Repeated Intravenous Infusions of a Cardiovascular Cell-Derived Extracellular Vesicle-Enriched Secretome

Background: Most of the effects of intramyocardially transplanted stem cells can be duplicated by the sole administration of their secretome but this approach has not yet been tested in heart failure (HF). Methods: The SECRET-HF phase I trial (NCT05774509) was designed according to a Bayesian optimal interval scheme to assess the effects of repeated intravenous infusions of a cellular secretome in 12 patients with a non-ischemic dilated cardiomyopathy. The main inclusion criteria are severe symptoms (NYHA Class III despite an optimal guideline-directed medical therapy), a reduced left ventricular (LV) ejection fraction (EF ≤40%) and ineligibility for a heart transplant. The Investigational Medicinal Product was derived from human induced pluripotent stem cells reprogrammed from a healthy donor and differentiated in cardiovascular progenitor cells (CPC). Following CPC culture in a dedicated "vesiculation" medium, the conditioned media were collected, filtered, enriched for extracellular vesicles, concentrated by tangential flow filtration and scaled out into glass vials stored at -80°C. Quality controls were implemented throughout the whole process which was conducted according to current Good Manufacturing Practices. Results: Three patients, out of the 4 of the initial low-dose cohort, have now been treated. All had been previously fitted with an automatic internal cardioverter defibrillator (AICD). The secretome was delivered intravenously 3 times, 3 weeks apart, at a dose of 20 x10 9 particles/kg for each infusion. By November, 2024, the follow-up will be 16, 9, 6 and 2 months for each of them (mean: 8 months). So far, none of the treated patients has experienced a dose-limiting toxicity; in particular, there have been no post-treatments ventricular arrhythmia detected by the AICD, no allo-immunization and no inflammation based on the enumeration of lymphocyte subpopulations by flow cytometry. At 6 months, the first patient improved to NYHA Class II with a decrease in echographic LVEDV and LVESV (from 108 mL/m 2 to 87 mL/m 2 and from 80 mL/m 2 to 60 mL/m 2 , respectively) and a concomitant increase in LVEF from 25% to 32%. At 1 month post-treatment, the second patient also reports a symptomatic improvement (NYHA Class II) with an increase in EF from 21% to 28%. Conclusions: This initial experience supports the safety of repeated intravenous administrations of a cardiovascular cellular secretome as a potential noninvasive and user-friendly treatment of severe HF.

Abstract 4137441: Online Cognitive Behavioral Therapy Targeting Psychological Distress Following Open Heart Surgery: An Uncontrolled Pilot Study

Background: Cardiac surgery is a significant procedure that reduces mortality and alleviates symptom burden in individuals with cardiovascular diseases. However, many patients develop depression and cardiac-related anxiety postoperatively, which negatively affects long-term prognosis and rehabilitation. There is a clinical need to develop scalable psychological treatments to mitigate these negative health effects. Objective: To investigate the feasibility and potential efficacy of a brief internet-delivered cognitive behavioral therapy (internet-CBT) intervention to reduce psychological distress in patients following cardiac surgery. Methods: The pilot study included 32 cardiac surgery patients (i.e., CABG, heart valve repair/replacement, aortic repair, or combined CABG and valve repair/replacement) with endorsed postoperative psychological distress and/or interference with daily life who underwent surgery from eight weeks to nine months prior to enrollment. Exclusion criteria included prior cardiac surgery with a ventricular assist device or heart transplant and severe medical or psychiatric illness. The internet-CBT targeted cardiac anxiety and depressive inactivity, lasted for five weeks, and was guided by clinical psychologists via text-based interactive online treatment modules. It included interoceptive exposure, in-vivo exposure, and behavioral activation. Self-assessments were completed at pre-treatment, post-treatment, and at 6-month follow-up. Results: Preliminary analyses post-treatment showed substantial pre-post improvements across multiple domains. Notable findings included significant reductions in depressive symptoms (Cohen’s d = 0.70; p = 0.04), cardiac anxiety (Cohen’s d = 1.53; p &lt; 0.001), and perceived severity of post-operative symptoms (Cohen’s d = 1.06; p = 0.006). Participants demonstrated high adherence to the treatment, with the large majority of participants completing all five treatment modules (83.3%). Satisfaction with the treatment was also high (25.5 points out of 32), as measured by the Client Satisfaction Questionnaire, and no adverse events were reported. Conclusion: This novel internet-CBT intervention post-cardiac surgery appears to be feasible, acceptable, and clinically promising in reducing postoperative psychological distress. It could be used as a viable adjunct treatment to enhance recovery post-cardiac surgery. These preliminary findings warrant further testing in a randomized controlled trial.

Abstract 4136745: How do sleep quality and heart failure symptoms impact functional status among patients with heart failure?

Background: Patients with heart failure (HF) frequently experience poor sleep quality and multiple HF symptoms, both of which are linked to diminished functional status. Poor sleep quality can manifest as prolonged latency, short duration, low efficiency, or difficulty staying asleep. HF symptoms encompass different dimensions: presence, frequency, severity, and distress of HF symptoms. Different dimensions of sleep quality and HF symptoms may uniquely influence functional status, necessitating tailored interventions, yet how individual dimensions of sleep quality and HF symptoms impact functional status remains unexplored. Research Question: how do individual dimensions of sleep quality and HF symptoms impact functional status in patients with HF? Methods: We studied 197 adults with HF (male: 66%, age: 62±11 yrs). The Pittsburgh Sleep Quality Index was used to assess seven dimensions of sleep quality: subjective sleep quality, latency, duration, efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. Four dimensions (i.e., presence, frequency, severity, distress) of 7 HF symptoms (e.g., shortness of breath, fatigue, swelling) were assessed using the Symptom Status Questionnaire-HF. Functional status was measured using the Duke Activity Status Index. Correlations and two multiple linear regression models (1 st model: 7 dimensions of sleep quality on functional status, and 2 nd model: 4 dimensions of HF symptoms on functional status) were conducted for data analysis. Results: Worse subjective sleep quality, longer latency, more sleep disturbances, use of sleeping medications, and higher levels of daytime dysfunction were correlated with poor functional status. All four dimensions of HF symptoms were negatively correlated with functional status. In the 1 st multiple linear regression model, more sleep disturbances (B=-3.91, p =.006) and higher daytime dysfunction (B=-5.70, p &lt;.001) were predictive of poor functional status (model R 2 =0.23, p &lt;.001). In the 2 nd multiple linear regression model, only higher frequency of HF symptoms (B=-.70, p =.022) predicted poor functional status (model R 2 =0.34, p &lt;.001). Conclusion: Increased sleep disturbances, daytime dysfunction, and frequency of HF symptoms were associated with poorer functional status in patients with HF. These findings underscore the importance of developing tailored interventions to address individual sleep problems and HF symptoms to improve functional status.

From immune response to mental health: neutrophils in schizophrenia

Schizophrenia is a multifaceted psychiatric disorder with a complex etiology that includes genetic, environmental, and immunological factors. Emerging research has increasingly focused on the role of the immune system, particularly neutrophils, in the pathogenesis of schizophrenia. Neutrophils, the most abundant type of white blood cells, are crucial in the body’s defense mechanisms against infections and in the regulation of inflammation. This review explores the evolving evidence that implicates neutrophils in schizophrenia, highlighting their potential contribution to the disorder’s onset and progression through mechanisms such as neuroinflammation and oxidative stress. Recent studies have demonstrated elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR) in individuals with schizophrenia, correlating with the severity of psychotic symptoms and cognitive impairments. Furthermore, genetic and molecular analyses have revealed abnormalities in neutrophil function and immune-related gene expression in schizophrenia patients. These findings suggest that neutrophil dysfunction and the resulting chronic inflammation could play a significant role in the disorder’s pathophysiology, affecting neuronal function and contributing to the clinical manifestations of schizophrenia. Neutrophil-related biomarkers, such as NLR, could aid in the diagnosis and monitoring of disease progression. Additionally, targeting neutrophil activity and associated inflammatory pathways presents a promising avenue for developing new therapeutic interventions. This review underscores the need for further research to elucidate the precise mechanisms by which neutrophils influence schizophrenia and to explore potential treatments that could improve outcomes for patients.

Investigation of GPM6B as a novel therapeutic target in Osteoarthritis.

Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Thus, we provided evidence that GPM6B act as a new target associated with OA.

Assessment of Babesia ovis pathogenicity in goats: implications for transmission dynamics and host resistant

Babesia ovis, commonly associated with ovine babesiosis, poses a significant threat to sheep health, often resulting in severe clinical manifestations and high mortality rates. However, the impact of B. ovis on goats has remained uncertain, prompting us to investigate its pathogenicity in caprine hosts. Experimental infections using B. ovis-infected blood inoculation and infected tick infestation, were conducted on spleen-intact (n=5) and splenectomized (n=5) goats. The experimental infection was performed using fresh blood obtained from a B. ovis-infected splenectomized sheep. One spleen-intact sheep served as a control for the experimental infection with B. ovis-infected Rhipicephalus bursa ticks. While all experimentally infected sheep (#501, #575) displayed severe clinical symptoms and high parasitemia, goats exhibited resistance, showing no significant clinical manifestations or sustained parasitemia. Notably, B. ovis was detected in two spleen-intact goats via nested PCR, prompting further investigation into their role as reservoirs for tick-borne transmission. These goats were then infested with Babesia spp.-free R. bursa larvae (0.1 gr) and adults (50 females and 50 males) for transstadial and transovarial transmission experiments respectively. Results indicated that chronically B. ovis-infected spleen-intact goats are not significant sources for maintaining the tick-borne transmission cycle of the parasite. These findings highlight the differential susceptibility of goats to B. ovis infection compared to sheep and their limited role as reservoirs for parasite transmission. Understanding the role of goats in B. ovis transmission and their resistance mechanisms can inform effective control measures and reduce economic losses in affected regions. Further research into caprine babesiosis and host immunological responses is essential to fully elucidate their possible role as reservoirs of the parasite, and underlying mechanisms of host susceptibility and parasite pathogenesis.

Abstract 4115222: Distinct Demographic, Cognitive, and Psychosocial Factors Associated with Different Types of Self-Care in Patients with Type 1 Diabetes and in Patients with Type 2 Diabetes

Background: Poor self-care in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) leads to increased diabetes complications and health costs. While the goal of self-management for patients with T1DM and T2DM is to maintain normal blood glucose levels, the major methods for achieving this differ (exogenous insulin delivery vs. a combination of self-care techniques, respectively). This implies that factors associated with self-care in the two groups may differ. Hypothesis: Distinct demographic, cognitive, and psychosocial factors are associated with overall self-care, diet, exercise, blood glucose testing, foot care, and smoking in patients with T1DM and T2DM, in separate models. Methods: In this cross-sectional, correlational study, data were collected from 148 patients with T1DM (n = 64, mean age: 51.3 years) or T2DM (n = 84, mean age: 62.5) using REDCap during 2023. The participants were recruited from various organizations, institutions, and ResearchMatch in the United States. Several multiple regression analyses were done to test the hypothesis. Results: Patients with T1DM had better self-care, including overall diabetes self-care, exercise, and blood glucose testing than the T2DM group. Older age (p = .003), lower body mass index (BMI) (p = .040), and stronger knowledge (p = .028) in the T1DM group (F[10,53]= 2.290, p = .026, R 2 = .302), while lower BMI (p = .045) and higher levels of self-efficacy (p &lt; .001) in the T2DM group were associated with better overall diabetes self-care (F[10,73] = 3.219, p = .002, R 2 = .306). Older age, lower BMI, stronger knowledge, stronger resilience, and lower self-esteem were associated with better self-care in diet, blood glucose testing, and/or foot care in the T1DM group, while lower BMI, stronger knowledge, higher levels of self-efficacy, and less severe depressive symptoms were associated with better self-care in diet, exercise, and/or blood glucose testing in the T2DM group. None were associated with smoking in both groups. Diabetes distress, self-compassion, and social support were not associated with any types of self-care. Conclusions: Factors associated with self-care differed based on types of self-care and types of diabetes, thus, supporting the hypothesis. When healthcare providers provide interventions to improve diabetes self-care in individual patients with diabetes, they need to consider types of diabetes, types of self-care, and distinct factors associated with each type of self-care.

Abstract 4143258: Sex Differences in Health Status Outcomes: Analysis of the ISCHEMIA Randomized Clinical Trial

Background: Despite a lesser extent and severity of coronary artery disease (CAD), women had a higher burden of angina than men in the ISCHEMIA trial, suggesting that other factors may explain symptom severity in women. We aim to describe demographic and clinical characteristics, as well as differences in care patterns, associated with health status differences in women, as compared with men, in the conservative and invasive treatment groups of the ISCHEMIA trial. Methods: The ISCHEMIA trial randomized participants with moderate or severe ischemia to a routine invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with catheterization reserved for GDMT failure. Health status was a key secondary outcome. Using linear regression models we compared raw and adjusted Seattle Angina Questionnaire (SAQ) scores in women and men at baseline and at 1 year, stratified by randomized treatment strategy. Within the invasive strategy, sex differences were adjusted for completeness of revascularization among those with ≥1 coronary stenosis ≥70%. Results: Of 4,617 ISCHEMIA participants with valid SAQ data, women had lower (worse) baseline SAQ summary scores (SS) throughout follow up (Figure) after adjustment for demographics and clinical characteristics, including severity of CAD (difference 5.4 points, 95% CI 4.0-6.7). Women had lower SAQ SS after adjustment for post-randomization treatment (i.e., medical therapy, achievement of risk factor goals and, in the invasive strategy, complete revascularization), 2.4 points lower (95% CI 0.7-4.1) in the conservative group (Figure), and 1.9 points lower than in men (95% CI 0.1-3.7) in the invasive group. Findings were similar for all SAQ subscales. Conclusions: Women with chronic coronary disease in ISCHEMIA had worse health status than men at baseline and 1 year later, which was not explained by demographic or clinical characteristics, intensity of medical therapy, or completeness of revascularization.

Positive Attributable Visual Sources Attenuate the Impact of Trigger Sounds in Misophonia

Abstract Misophonia is characterized by strong negative reactions to everyday sounds, such as chewing, slurping or breathing, that can have negative consequences for daily life. Here, we investigated the role of visual stimuli in modulating misophonic reactions. We recruited 26 misophonics and 31 healthy controls and presented them with 26 sound-swapped videos: 13 trigger sounds paired with the 13 Original Video Sources (OVS) and with 13 Positive Attributable Visual Sources (PAVS). Our results show that PAVS stimuli significantly increase the pleasantness and reduce the intensity of bodily sensations associated with trigger sounds in both the misophonia and control groups. Importantly, people with misophonia experienced a larger reduction of bodily sensations compared to the control participants. An analysis of self-reported bodily sensation descriptions revealed that PAVS-paired sounds led participants to use significantly fewer words pertaining to body parts compared to the OVS-paired sounds. We also found that participants who scored higher on the Duke Misophonia Questionnaire (DMQ) symptom severity scale had higher auditory imagery scores, yet visual imagery was not associated with the DMQ. Overall, our results show that the negative impact of misophonic trigger sounds can be attenuated by presenting them alongside PAVSs.

AVALIAÇÃO NEUROPSICOLÓGICA NO TRANSTORNO DE ANSIEDADE GENERALIZADA NA INFÂNCIA E ADOLESCÊNCIA

This study aimed to explore the role of neuropsychological assessment in enhancing the efficacy of Generalized Anxiety Disorder (GAD) treatment in children and adolescents. Given the significant influence of emotional development during this life stage on the manifestation of fears and worries, a comprehensive understanding of each individual's psychological profile is essential. The high prevalence of GAD in childhood and adolescence underscores the critical need for early intervention to prevent chronic conditions and long-term consequences. A literature review reveals that psychological assessment in this population presents unique characteristics and is vital for identifying specific GAD symptoms, assessing symptom severity, and pinpointing preserved abilities. Additionally, neuropsychological assessment offers insights into how anxiety impacts the daily functioning of children and adolescents, aiding in the selection of tailored interventions. However, it is crucial to recognize that neuropsychological assessment is a complex process, and results must be interpreted cautiously considering the multifaceted nature of anxiety disorders and the influence of various factors. In conclusion, further research is imperative to deepen our understanding of the psychological dimensions of GAD in childhood and adolescence, thereby improving clinical practices and ensuring more effective treatment for this population.

Abstract 4134417: Cardiotoxicity Conundrum: Distinguishing Immune Checkpoint Inhibitor Myocarditis from Fluorouracil Cardiotoxicity in Concurrent Therapy

Case Description: The patient is a 37-year-old male with metastatic gastroesophageal junction adenocarcinoma presenting with chest pain and dyspnea two days after initiation of leucovorin, fluorouracil, oxaliplatin (FOLFOX), and nivolumab therapy. He was tachycardic and hypotensive with elevated cardiac biomarkers and globally reduced left ventricular systolic function. Suspecting immune checkpoint inhibitor (ICI) myocarditis versus fluorouracil (5-FU) cardiotoxicity, he was treated simultaneously for both. After starting high-dose steroids and before uridine triacetate, he had improved symptoms, cardiac function, biomarkers, and invasive hemodynamics. Though his endomyocardial biopsy did not show inflammatory cell infiltrates, his CMR demonstrated increased T1 and T2 relaxation times consistent with myocarditis. Testing revealed normal dihydropyrimidine dehydrogenase (DPD) activity. He completed uridine triacetate and was discharged on a steroid taper. At follow-up, he remained clinically stable, tolerating oxaliplatin and docetaxel (FLOT) initiation and nivolumab rechallenge without 5-FU. Discussion: This case is challenging as the presentation does not conclusively identify a causative agent. The patient’s symptom severity suggests ICI myocarditis, while the early onset points to 5-FU cardiotoxicity. His quick recovery of cardiac function after medication cessation suggests 5-FU-associated Takotsubo cardiomyopathy. His improvement after steroids raises concern for an adverse immunologic response as in ICI myocarditis or idiosyncratic reactions to oxaliplatin with 5-FU. This patient received ICI therapy and chemotherapy, increasing his risk for cardiac immune-related adverse events. His protracted 5-FU infusion increased his risk for 5-FU cardiotoxicity, but his normal DPD activity mitigates this risk. Although his biopsy was negative, it cannot exclude ICI myocarditis. By the IC-OS 2021 consensus, he meets the criteria for ICI myocarditis presenting 48 hours after nivolumab exposure with cardiogenic shock, elevated cardiac biomarkers, decline in cardiac function, and CMR with elevated T1 and T2 relaxation times. Yet, his biomarkers remained normal with nivolumab rechallenge, arguing against ICI myocarditis and suggesting 5-FU as the culprit. Early recognition and differentiation of the culprit in concurrent therapies impact management and future treatment options. Rechallenge carries risk and requires interdisciplinary collaboration to ensure patient safety.

Abstract 4134619: A Novel Missense Mutation in TNNT2 Gene in a Lebanese Pedigree With Ebstein Anomaly And Wolf-Parkinson-White Syndrome: A Case Report

Background: Ebstein anomaly (EA) is a rare congenital heart defect occurring in 1.2 to 5 in 100,000 live births, characterized by a downward displacement of the tricuspid valve, thin-walled right ventricle, and tricuspid valve regurgitation. It can present variably from asymptomatic cases to severe symptoms like arrhythmias and right-sided heart failure. EA is often associated with other anomalies such as interatrial communication and mitral valve prolapse. The condition can lead to accessory atrioventricular pathways, frequently resulting in Wolff-Parkinson-White syndrome (WPW), which involves abnormal heart electrical activity and increases the risk of sudden cardiac death. While the genetic basis of EA is not fully understood, it appears to involve multiple genes like FLNA and NKX2-5, MYH6, MYH7 suggesting a complex polygenic inheritance pattern. TNNT2 is known to be associated with Cardiomyopathy but has not been previously associated with EA and WPW. Case: In this report, we present findings from a lebanese family with EA, comprising 2 affected individuals. Whole exome sequencing in the affected individuals identified a pathogenic variant in the TNNT2 gene at coding strain position 260 (a missense mutation: C to T), resulting in the substitution of Proline with Leucine at position 87 in affected individuals (Figure 1). No variants were detected in any other candidate gene examined. Individuals I:1 and II:2 were found to be normal, with no EA findings on echocardiography. Methods: Whole exome sequencing in the patients involved collecting blood samples after obtaining consent. These samples were sent to Centogene lab, where genomic DNA is enzymatically fragmented. The regions of interest are then enriched using DNA capture probes, facilitating detailed genetic analysis. Results: The whole exome sequencing identified a heterozygous missense mutation in both the father and his daughter. This nonsynonymous variant is located on chromosome 1 (GRCh37) in the TNNT2 gene region. The specific variant, NM_001276345.1:c.260C&gt;T p.(Pro87Leu), was found in both individuals. Conclusion: In conclusion, the genetic basis of EA is rather complex and remains poorly understood. It is established that mutations in the TNNT2 gene are linked to several cardiomyopathies, none of them overlap with the described phenotype of our patients. In this report, we therefore confirm the potential role of TNNT2 gene mutation in the genetic basis of familial EA with WPW.

Adaptive emotion regulation might prevent burnout in emergency healthcare professionals: an exploratory study.

Emergency department (ED) professionals face a high risk of physical, mental, and emotional strain, which can lead to burnout. Burnout arises from chronic work-related stress, which negatively impacts ED professionals, the healthcare system, as well as patient outcomes. Effective adaptive emotion regulation strategies (ERS) are crucial for handling stress in healthcare workplaces and mitigating the risk of burnout. High-quality patient-professional relationships, including empathy, significantly improve patient compliance and disease outcomes. This cross-sectional exploratory study aims to investigate the relationship between mental distress, burnout, adaptive and maladaptive ERS among healthcare professionals in an ED. A total of 159 ED workers participated in an online survey. Emotion regulation was assessed using the Cognitive Emotion Regulation Questionnaire, while burnout and mental distress were measured using the Maslach Burnout Inventory and the Depression, Anxiety, and Stress Scale. The findings revealed that more than 20% of participants displayed severe symptoms of stress (N = 35), anxiety (N = 36), and depression (N = 31), and only 10.7% (N = 27) had no signs of burnout. Despite these findings, it appears that the majority of ED professionals primarily utilise adaptive ERS (91.8%, N = 146). However, as burnout levels increased, the use of adaptive ERS declined compared to maladaptive strategies. Regression analysis identified several significant predictors of Emotional Exhaustion, Depersonalisation, and reduced Personal Accomplishment, including gender, age, physical exercise, smoking, sedative usage, stress, depression, maladaptive strategies and adaptive strategies such as positive reappraisal. These study results highlight the urgent need to address workplace stress, burnout, and mental distress among healthcare professionals in EDs. Implementing effective strategies for adaptive emotion regulation and promoting a supportive work environment can help mitigate burnout and enhance the well-being of ED workers, ultimately benefiting patient care and outcomes.

Clinical Characteristics of Inpatients with Schizophrenia Spectrum Disorder Treated with Electroconvulsive Therapy: A Population-Level Cross-Sectional Study: Titre: Caractéristiques cliniques des patients hospitalisés présentant un trouble du spectre de la schizophrénie et traités par électrochocs : Une étude de population transversale.

Electroconvulsive therapy (ECT) is an evidence-based treatment for schizophrenia when anti-psychotic medications do not sufficiently control symptoms of psychosis or rapid response is required. Little is known about how it is used in routine clinical practice. The aim of this study was to identify the association of demographic and clinical characteristics with administration of ECT for schizophrenia spectrum disorders (SSD). Among psychiatric inpatients with a diagnosis of SSD in Ontario, Canada (2006-2023), patient-level socio-demographic and clinical characteristics were described in those who did and did not receive ECT. We used multi-variable logistic regression to assess the association between patient-level characteristics and administration of ECT during index hospitalization. From 164,632 admissions, 2,168 (1.3%) involved exposure to ≥1 inpatient ECT procedure. Compared to those not receiving ECT, those receiving ECT were older, had higher rates of pre-admission medication use, medical and psychiatric comorbidities, outpatient mental health service use, but lower rates of substance use disorders. In the multi-variable logistic regression model, patient-level characteristics most strongly associated with receiving inpatient ECT were the presence of catatonia (odds ratio [OR]: 5.83; 95% confidence interval [95% CI]: 4.01-8.46), comorbid depression (OR: 2.49; 95% CI: 2.07-2.98), obsessive-compulsive disorder (OR: 2.16; 95% CI: 1.55-3.00), while characteristics most strongly associated with not receiving inpatient ECT were myocardial infarction (OR: 0.44; 95% CI: 0.20-0.95) and family conflict towards patient (OR: 0.47; 95% CI: 0.31-0.71). Neither severity of psychotic symptoms, non-command auditory hallucinations nor delusions were associated with administration of ECT. While characteristics associated with the use of ECT are generally consistent with the indications for ECT (e.g., catatonia, mood disorders), ECT is rarely used amongst individuals with SSD. Severity of psychotic symptoms was not associated with the use of inpatient ECT suggesting an opportunity to increase the use of ECT in this population.

Quantifying neurobehavioral profiles across neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders.

To examine neurobehavioral findings in three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome [mutations in the NFIX gene], and SYNGAP1-related disorder), a mixed group of other neurodevelopmental genetic syndromes (NDGS), idiopathic neurodevelopmental disorder, and neurotypical control participants. Using a longitudinal case-control design, caregivers reported neurobehavioral information for 498 participants (PTEN hamartoma tumor syndrome n = 112, Malan syndrome n = 24, SYNGAP1-related disorder n = 47, other NDGS n = 72, idiopathic neurodevelopmental disorder n = 54, neurotypical siblings n = 74, and unrelated neurotypical control participants n = 115) at three timepoints (baseline, and 1-month and 4-month follow-ups) using the online-administered Neurobehavioral Evaluation Tool (NET). NET scales had good scale and test-retest reliability. Unique patterns of neurobehavioral findings emerged, with SYNGAP1-related disorder and Malan syndrome showing generally more severe symptom and skill patterns than for other groups of patients. Patterns could be partly accounted for by estimated cognitive level, speech level, and the presence of autism spectrum disorder. However, even when accounting for these factors, group differences remained. Reliable change indices are reported. Genetic syndromes associated with neurodevelopmental disorders present with unique neurobehavioral profiles that can inform selection of outcome measures in future clinical trials. The NET may be a useful screening and monitoring instrument in clinical practice, where frequent in-person clinic attendance is difficult for many patients.