United States

Background: Psoriasis is one of the most prevalent chronic inflammatory skin conditions; however, its effects span much farther than its cutaneous manifestations. This study aims to assess the impact of biologic treatments on the development of depressive comorbidities in patients with psoriasis.

Methods: A retrospective chart analysis with data from TriNetX was performed for patients after propensity matching on TNF-α inhibitors (Cohort A), IL-17 inhibitors (Cohort B), and IL-23 + IL-12/23 inhibitors (Cohort C).

Results: All comparator groups showed a statistically significant decrease in new onset MDD, new onset DE, and new prescription of antidepressants. The risk ratios for both new onset MDD and DE, as well as odds ratio for new antidepressant prescription, respectively, were as follows: for Cohort A, 1.857 (CI: 1.233-2.797), 1.416 (CI: 1.176-1.705), 1.169 (CI: 1.031, 1.326); Cohort B, 2.636 (CI: 1.32-5.265), 2.35 (CI: 1.63-3.387), 1.169 (CI: 1.031, 1.326); Cohort C, 2.586 (CI: 1.687-3.964), 2.489 (CI: 1.965-3.154), 1.975 (CI: 1.71, 2.281.

Limitations: The TriNetX database has inherent limitations based on diagnosis codes and lack of sufficient data on cutaneous response.

Conclusion: Our study provides compelling evidence that biologic therapies for psoriasis, including IL-17, IL-12/23, IL-23, and TNF-𝛼 inhibitors, significantly reduce the risk of new diagnoses of MDD, new depressive episodes in patients, as well as lower the odds of starting a new prescription of antidepressant.

AMA Research Challenge 2024 

Impact of biologic treatments on the development of depressive comorbidities in patients with psoriasis

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Abstract Title
Investigating the Association Between Ozempic Use and Psoriasis: An Analysis of FDA Adverse Event Reporting System Data from 2019-2024.


Background
GLP-1 agonists, including Ozempic, are prescribed to treat type 2 diabetes. While it is used for blood glucose control, the added advantage of Ozempic is weight reduction in patients with and without diabetes; because of this, its usage has increased over the years and has run into a shortage issue. Even though Ozempic is very effective for weight reduction and diabetes management, there have been cases described with adverse events, including psoriasis. This study aims to investigate a potential association between using Ozempic and psoriasis as an adverse event by analyzing cases of reported adverse events from the FDA Adverse Event Reporting System from 2019-2024.

Methods
In the FAERS database, the search terms "Ozempic" and "psoriasis" were used to identify reported cases of psoriasis in patients treated with Ozempic from 2019 to 2024. Non-plaque psoriasis variants, including pustular, guttate, and erythrodermic psoriasis, were excluded during data retrieval. Descriptive statistics, including Chi-Square tests, correlation analysis, and trend visualizations, were used to analyze case counts, age, gender, and severity. 

Results
In the FAERS database, from 2019 to June 2024, a total of 20 cases of psoriasis associated with Ozempic use were identified. Most cases lacked specified age data. The gender distribution was nearly equal, with 10 cases in males, 9 in females, and 1 with unspecified gender. Hospitalization was reported in one case. Statistical analysis using a Chi-Square test revealed no significant association between age, gender, and the development of psoriasis (χ² = 4.52, p = 0.34, dof = 4). A statistically significant association between Ozempic use and the development of psoriasis was observed (χ² = 5.75, p = 0.026, dof = 1). A trend analysis signified a slight increase in psoriasis cases over time, with the highest reported cases occurring in 2023. However, the correlation was weak (r = 0.147).


Conclusion
The study's findings imply that Ozempic use may be related to the development of psoriasis. However, the study is significantly limited by its small sample size, lack of detailed patient demographics, and potential reporting biases. Furthermore, confounding factors, such as the use of other medications or comorbid conditions, were not analyzed, further limiting the study’s initial findings. Additionally, to validate our study's preliminary findings and understand the potential biological mechanism involved in Ozempic leading to psoriasis, more extensive, controlled studies are required. The studies can help improve patient management strategies and risk assessment for Ozempic treatment. 




Investigating the Association Between Ozempic Use and Psoriasis: An Analysis of FDA Adverse Event Reporting System Data from 2019-2024.

Biologics have revolutionized psoriasis treatment, yet there remains limited data regarding ocular adverse events (AEs) associated with these therapies. Using the FDA Adverse Event Reporting System (FAERS), we investigated the most commonly reported ocular AEs linked to biologics approved for psoriasis from 1998 to 2024. A total of 70,884 reports related to 13 biologics were analyzed. The most frequently reported AEs were visual impairment (10,569), cataracts (9,457), blurred vision (7,506), and uveitis (5,654). Adalimumab, etanercept, and infliximab accounted for the majority of severe ocular AEs, including 52% of blindness cases. Females represented 64.7% of cases, and AEs were uncommon in children and those over 85 years of age. These findings underscore the importance of monitoring for ocular complications in patients on biologics and suggest further research to assess long-term safety and preventive strategies.

Ocular adverse events associated with biologics approved for psoriasis: an FDA Adverse Event Reporting database study

Introduction: Despite comprising the minority of patients diagnosed with skin cancers, racial and ethnic minority groups experience worse prognoses and are at increased risk for adverse outcomes compared to non-Hispanic, White patients. We aim to quantify disparities in treatment-associated outcomes across race and ethnicity for patients with cutaneous malignancies of the head and neck. 
Methods: We analyzed patients diagnosed with melanoma and nonmelanoma skin cancers between 2010 to 2021 using data from the National Cancer Database (NCDB). The primary outcome variable, treatment refusal, was examined via logistic regression. Secondary variables included days from diagnosis to treatment, tumor depth, and mortality. These were analyzed using multi-way ANOVA and binary logistic regression.
Results: Of 151,733 patients analyzed, most were non-Hispanic White (99%) and male (71%). Black patients had the greatest odds of treatment refusal (4.166, 95% CI: 2.054-8.452, p<0.001) across all cutaneous malignancies of the head and neck. Black and Hispanic patients also had increased times from diagnosis to treatment (p<0.001). Black patients had a higher odd of 90-day mortality compared to non-Hispanic White patients (p<0.001). This coincided with greater tumor depth in Black and Hispanic patients compared to non-Hispanic White patients (p<0.001).
Conclusions: Black patients are more likely to refuse treatment for cutaneous head and neck malignancies overall and both Black and Hispanic patients experience more treatment delays. These findings may relate to the increased 90-day mortality among Black patients and increased tumor depth for both Black and Hispanic patients. Further investigation into quality of life and functional impairment are warranted alongside culturally sensitive interventions to reduce these disparities.

Racial & Ethnic Disparities in Treatment Refusal for Head & Neck Cutaneous Malignancies

Background: In the treatment of keratinocyte carcinoma, curettage alone has been described as a simpler, less expensive, and quicker method than electrodessication and curettage; however, there are limited studies examining recurrence rates for such lesions.
Objective: To investigate the 5-year recurrence rates of keratinocyte carcinoma treated with curettage alone and compare these results to previously reported recurrence rates for electrodessication and curettage.
Methods: A retrospective cohort and interview study determined 5-year recurrence rates for 1853 total lesions treated with curettage alone using chart review data and patient phone calls. 
Results: Our study yielded a per-protocol 5-year recurrence rate of 2.41% for BCCs, 4.52% for SCCs, and an average of 3.71% across both types of keratinocyte carcinoma. Lesions on the head and neck displayed a significantly greater recurrence rate of 7.18% when treated with curettage alone.
Limitations: We were limited to the use of previously published data to determine recurrence rates for lesions treated with full electrodessication and curettage.
Conclusion: Curettage alone provides comparable efficacy in curing keratinocyte carcinoma when compared to electrodessication and curettage.


Recurrence Rates of Keratinocyte Carcinoma Treated with Curettage Alone, a Retrospective Cohort and Interview Study

Background
Dissecting cellulitis (DC), also known as perifolliculitis capitis abscedens et suffodiens or Hoffman disease, is characterized by a perifollicular inflammatory infiltrate, comprising lymphocytes, predominantly CD8+ T cells, and neutrophils. Its etiology is attributed to aberrant follicular keratinization, resulting in follicular blockage and subsequent bacterial infection. DC may manifest concomitantly with conditions such as acne conglobata and inverse acne, forming part of the follicular occlusion triad. Symptoms of DC encompass tender nodules, alopecia, and lesions that, despite incision and drainage, demonstrate recurrence. Interconnected sinus tracts form in DC which can either be deep sinus tracts or tortuous ridges linking the nodules and abscesses. Treatment modalities for DC encompass isotretinoin, dapsone, intralesional steroid injections, and doxycycline. Tobacco smoking is recognized as a significant risk factor for the development and subsequent exacerbation of DC. In recent times, Electronic Nicotine Dispensing Systems (ENDS) or vaping has gained popularity; however, the potential risk of DC linked with vaping remains unclear. We hypothesized that the risk of developing DC might be elevated in individuals with a vaping history due to increased exposure to toxic metabolites. Subsequently, we compared the risk of DC development between individuals using vaping devices and tobacco products.

Methods
We conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, a comprehensive electronic health records (EHR) system. Cohorts included patients with vaping history (Cohort A) compared to tobacco smokers (Cohort B). Propensity score matching was utilized to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities.

Results
Risk of DC development for Cohort A was 2.53 %, compared to Cohort B 3.94% (p<0.0001 (95% CI (1.269, 1.912); Risk ratio: 1.557).

Conclusion
Benzo(a)pyrene, found in cigarette smoke, has been linked to vitamin A deficiency which can increase the risk of intraductal keratinization of the epithelial cells, potentially obstructing ductal structures. Chemical profiles of ENDSs vary due to manufacturing differences and addition of various flavors and stabilizing agents. While toxic chemicals related to tobacco smoking have been extensively studied, the ENDSs chemicals and their effect on the human body remains a poorly understood area. DC may be misdiagnosed as cystic acne therefore, a punch biopsy is required for accurate diagnosis. Treatment of DC should target both infection and inflation; thus, azithromycin and doxycycline are commonly used for their anti-inflammatory effect. Adalimumab and TNF-α have been reported to be efficacious in treatment of DC.

Risk Associated with Electronic Nicotine Dispensing Systems versus Tobacco Use and Development of Dissecting Cellulitis

Background: Palmoplantar pustulosis (PPP) is a chronic, debilitating inflammatory skin disorder characterized by erythematous pustules and desquamation on the palms and soles with severe impact on quality of life. While IL-17 pathways have been implicated in PPP pathogenesis, clinical trials with IL-17 inhibitors have yielded conflicting results, underscoring the need for a deeper understanding of its underlying mechanisms.
Methods: We employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to analyze skin biopsies from PPP patients (n=3) and healthy controls (n=5). We identified distinct cellular populations, their gene expression profiles, and interactions contributing to PPP pathology.
Results: We analyzed 32,364 cells using scRNAseq, identifying nine major cell types and revealing significant differences in cellular compositions between lesional PPP, nonlesional skin, and healthy controls. Within the lymphocyte population, regulatory T cells (Treg) and T helper 17 cells (Th17) were exclusively presented in PPP samples. Further characterization uncovered two distinct Th17 subpopulations with differential cytokine expression and regulation. A subpopulation termed “regulatory Th17” expressed immune regulatory molecules FOXP3 and CTLA4 and demonstrated elevated levels of IL17F and IL26 in lesional cells. These cells directly interact with IL36G+ supraspinous keratinocytes, amplifying the inflammatory response. Immunohistochemistry analysis further confirmed elevated levels of IL-26 and IL-17 in lesional skin, implicating these cytokines in the inflammatory cascade associated with PPP.
Conclusions: Our findings underscore the complexity of PPP pathogenesis, involving unique immunological environments and T cell plasticity. The identification of regulatory Th17 cells as major IL-26 producers and their interaction with inflammatory keratinocytes suggests potential therapeutic targets. 


Single-Cell Analysis Reveals Distinct Subpopulations of T Cells and Elevated
IL-26 and IL-17 Levels in Palmoplantar Pustulosis Lesions

Background: Basal cell carcinoma (BCC) is the most prevalent skin malignancy, with a growing global incidence attributed to increased UV exposure and an aging population. While early-stage BCC can be treated with Mohs surgery and photodynamic therapy, options for advanced cases are limited. Existing systemic therapies, including SMOOTHENED inhibitors that target the Hedgehog (HH)-signaling pathway in BCC, are associated with significant adverse effects, such as muscle spasms, hair loss, and teratogenicity. Additionally, the emergence of resistance to these inhibitors underscores the need for diversifying systemic treatment options. This study aims to deepen our understanding of HH-signaling pathway, with the goal of identifying FDA-approved drugs with favorable genetics profile to disrupt this pathway.

Methods: Expression levels of mRNA transcripts for six key genes involved in BCC pathogenesis—Gli1, Gli2, Gli3, Shh, Ptch1, Ptch2, and Smo—were acquired from 269 human neck skin tissues in the Gene Network 2.0 database. Pearson Correlation Matrix analysis revealed statistically significant correlations among these genes (p < 0.05). Signaling network analysis with NetworkAnalyst 3.0 identified key molecular pathways shared among these genes. Subsequently, a protein-protein interaction (PPI) network was constructed based on the six key genes using the IMEx Interactome database, and functional annotation analysis was conducted using KEGG, REACTOME, and Gene Ontology databases to identify associated biological processes, molecular functions, and cellular components. Lastly, a Protein-Drug Network analysis was performed using DrugBank 5.0 database to identify FDA-approved drugs capable of inhibiting protein components of the PPI network.

Results: Pearson correlation matrix analyses revealed significant positive correlations among Gli1, Gli2, Ptch1, and Ptch2 expressions. Notably, positive correlations were observed for Gli1-Gli2 (r = 0.651, p < 0.05), Ptch1-Ptch2 (r = 0.734, p < 0.01), and Gli1-Ptch1 (r = 0.528, p < 0.05). Signaling network analysis identified notable pathways, such as 'Chemokine signaling,' ‘RAS signaling,’ ‘Proteoglycans in cancer,’ and ‘Apelin signaling,’ latter of which has not been previously explored in the context of BCC pathogenesis. Subsequent PPI networks identified 198 proteins regulating various cancer-related pathways, specifically Histone Deacetylase 1 (HDAC1), AKT Serine/Threonine Kinase 2 (AKT2), Phosphatase and Tensin Homolog (PTEN) that are frequently dysregulated in cancerous cells. Subsequent functional annotation analysis identified ‘Positive regulation of transcription,’ ‘Chromatin binding,’ and ‘Nucleus’ as the primary associated biological process, molecular function, and cellular compartment. Finally, Protein-Drug analysis of the PPI network identified six FDA-approved drugs—Amitriptyline, Nintedanib, Pazopanib, Ponatinib, Regorafenib, and Sorafenib—that may disrupt the PPI network by targeting proteins involved in 'PI3K-AKT signaling pathway,’ 'RAS signaling pathway,' and 'Chemokine signaling pathway.'

Conclusion: This study provides deeper insights into the molecular components and signaling pathways in BCC pathogenesis. The significant correlations and identified pathways highlight interdependent regulation of Gli1, Gli2, Ptch1, and Ptch2 expressions. Identifying FDA-approved drugs that may disrupt HH-signaling pathways suggests potential therapeutic strategies to diversify treatment for advanced BCC. These findings support repurposing existing drugs to improve treatment options, warranting further research and clinical trials.

Systems Genetics of Hedgehog-signaling Pathway May Incentivize Repurposing of FDA-approved Drugs Against Advanced Basal Cell Carcinoma

Background: Atopic Dermatitis (AD) is a chronic, pruritic inflammatory cutaneous disease that affects people of all ages and demographics. In the United States, AD affects over 30 million people and 10.2% of adults. AD is known to be cumbersome and financially taxing, significantly affecting patients’ quality of life (QoL). As disease prevalence increases and new therapies arise, a better understanding of the socioeconomic burden becomes critical. The objective of this study is to assess the financial implications across various socioeconomic backgrounds and community types from the patient perspective within a single institution that serves rural, suburban, and urban areas.

Methods: A 22-question cross-sectional survey was conducted through telephone calls. Inclusion criteria included patients ≥18 years old with an ICD code for AD seen at our institution over the past 10 years. Patients were adults of varying ages, genders, races, and ethnicities. Patients self-reported information on their AD diagnosis, socioeconomic status, education level, affordability, expenses related to their AD, and factors affecting their QoL. Statistical analysis was performed using SPSS.

Results: Sixty-four patients participated in the survey, with a response rate of 78%. Responders were predominantly female (55%), with a mean age of 41. Participants were 48% White or Caucasian, 36% Black or African American, and 16% Asian or Asian American. Self-reported disease severity was labeled as mild (17%), moderate (33%), or severe (50%). Yearly income levels were reported as less than $50k (23%), $50-100k (14%), $100-150k (16%), more than $150k (20%), and 27% declined to answer. Thirteen respondents (21%) reported that they had been unable to afford their medications at some point, only three had household incomes of less than $50,000/year. Most respondents (36%) stated that over-the-counter treatments and supplies were the most expensive aspects of their AD care. The financial burden of AD for each income level did not differ significantly across income levels. Regarding education, 36% had less than a college degree, 42% earned a college degree, and 22% earned a postgraduate degree. Most individuals answered that they almost or completely understood their disease and treatment options when asked (81%). When asked to select up to three factors from a list that affect their QoL due to AD, 14 respondents identified financial burdens, five chose transportation, five selected access to medical care, and two indicated access to supplies. These factors did not vary significantly across different income groups.

Conclusions: Our study found that one in five patients have been unable to afford treatment at some point. The understanding of disease and treatment options may not be based on education level but rather on health literacy. Understanding the socioeconomic impact of disease facilitates better resource allocation and knowledge of how we can better serve the evolving patient population.

The Influence of Finances and Education on Quality of Life in Atopic Dermatitis

Title
Unraveling Allergy-Related Factors Contributing to Hair Loss

Background 
Frontal Fibrosing Alopecia, Lichen Planopilaris, and Central Centrifugal Cicatricial Alopecia are inflammatory alopecias that can be challenging to treat. Previous studies showed LPP and FFA patients are significantly more likely to have positive patch tests and evidence of allergic contact dermatitis. Allergen avoidance improved scalp inflammation. Those studies did not include CCCA common in people of African descent. The purpose of this study was to determine if our data at one institute was similar to previous studies, while including CCCA patients. 

Methods
A retrospective chart review was conducted on all hair loss patients who received patch testing from January 2021 to June 2023 at KMC Dermatology in Mission, Kansas. Patients were stratified based on diagnosis of FFA, LPP, or CCCA, patch testing, allergens, and anti-inflammatory therapy. 

Results
46 of the 80 total patients (57.55%) had a positive patch reaction. Of the 48 LPP patients, 30 (62.5%) had a positive reaction. The majority of the patients that tested positive had LPP (30 of 46). Of the 10 FFA patients, 7 (70%) had a positive reaction. Of the 9 CCCA patients, 5 (55.56%) had a positive reaction. The most common allergen was toluenediamine sulfate (6 patients, 7.5%). 

63 of the 80 (78.75%) total patients received anti-inflammatory therapy. Of the 48 patients with LPP, 39 (81.25%) received anti-inflammatory therapy. Of the 10 patients with FFA, 7 (70%) received anti-inflammatory therapy. Of the 9 patients with CCCA, 8 (88.89%) received anti-inflammatory therapy. The most common anti-inflammatory was Doxycycline (34 patients, 42.5%). 

Conclusion
57.5% of patients had a positive reaction. Similar to previous studies, a significant number of patients had a positive patch test. It demonstrated the most common allergens were toluenediamine sulfate, benzoyl peroxide, and propylene glycol. Previous studies lacked CCCA and including these patients offers insight on this understudied disease. 55.56% CCCA patients were patch test positive, with the most common allergen being propylene glycol. 78.75% of patients received anti-inflammatory therapy. The most common were Doxycycline, Naltrexone, and Tofacitinib. Lower magnitude of reaction to the patch testing can result if the patient is on anti-inflammatory medication. It’s possible that a reduction in positive results occurred as a large majority of the patients received these medications. Overall, the study confirmed that patients with LPP, FFA, and CCCA can benefit from patch testing evaluation. Encouraging patch testing in these patients, may help to identify allergic triggers, potentially limiting further hair loss.

Unraveling Allergy-Related Factors Contributing to Hair Loss

Study Objectives: Patients who prefer to communicate in a language other than English are vulnerable to the consequences of medical communication barriers. Studies of Non-English Language Preferred (NELP) and English Language Preferred (ELP) patients have shown differences in rates of hospital admission and wait times, factors related to increased costs and lower patient satisfaction. However, few studies consider languages other than Spanish or account for the patient’s acuity level when they present to the Emergency Department (ED). This study investigates differences in care between NELP and ELP patients across three ED operational metrics: hospital admission rate, time from arrival to room, and time from arrival to disposition.

Methods: This retrospective cohort study used electronic health records from January 2020 to December 2020 from an urban academic medical center. Data extracted included age, gender, language preference, disposition, and Emergency Severity Index Score (ESI). NELP patients were languages were grouped into three language categories: Spanish, Chinese (Mandarin, Cantonese, Taishanese, Taiwanese, and Zhongshan-Chinese dialect), and Other (all remaining languages). The primary outcomes were hospital admission rate and times from arrival to the treatment room and arrival to disposition. Data was analyzed with chi-squared tests, logistic, and linear regressions.

Results: Of the 58,079 unique ED encounters in the study period, 26.4% (15,307) patients identified as NELP. Within NELP patient encounters, 75.0% preferred Spanish, 13.9% preferred Chinese, and 11.1% preferred another language. NELP patients had a higher admission rate than ELP (22.6% vs 20.0%, p<0.001), which after adjusting for age and acuity, demonstrated a 15% increased odds (p<0.001). NELP patients waited an average 5.4 minutes longer to be roomed (p<0.001) and 15.6 minutes longer until disposition (p<0.001). This discrepancy was greater for lower acuity patients, with ESI 5 Spanish and Chinese language-preferred patients waiting a longer average 50.4 and 90.6 minutes respectively ( p<0.001; p<0.05).

Conclusion: Even after adjusting for acuity level and age, NELP patients were at higher odds of admission and experienced disparate wait times, particularly at lower acuity levels. Decreased ED throughput not only affects patient experience but can delay treatment for more emergent patients. These disparities demonstrate opportunities to improve ED efficiency and the need to improve health equity.

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Impact of biologic treatments on the development of depressive comorbidities in patients with psoriasis

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Investigating the Association Between Ozempic Use and Psoriasis: An Analysis of FDA Adverse Event Reporting System Data from 2019-2024.

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