Jacobs Institute of Women's Health
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Lack of Association of Emotional Distress With Insulin Initiation in the GRADE Randomized Diabetes Comparative Effectiveness Trial
No full textPurposeThe purpose of this study is to evaluate whether higher emotional distress (depressive symptoms or diabetes distress) was associated with a lower likelihood of basal or rapid-acting insulin initiation among participants enrolled in the GRADE Emotional Distress Substudy (EDS).MethodsIndividuals with type 2 diabetes \u3c10 years duration on metformin alone were randomized to add 1 of 4 glucose-lowering drugs. Per protocol, participants were expected to start basal or rapid-acting insulin rescue therapy after reaching secondary or tertiary glycemic outcomes (A1C \u3e7.5%). Depressive symptoms and diabetes distress were assessed ≤12 months prior to outcome confirmation. Multinomial and binomial logistic regression models examined associations of depressive symptoms and diabetes distress with basal insulin initiation and rapid-acting insulin initiation, respectively.ResultsOf the 525 participants expected to start basal insulin, 30.9% initiated ≤6 weeks, 35.2% initiated \u3e6 weeks, and 33.9% never initiated. Of the 325 participants expected to start rapid-acting insulin, 67.4% never initiated. Neither depressive symptoms nor diabetes distress were associated with starting basal or rapid-acting insulin.ConclusionsIn the GRADE EDS, approximately one-third of participants did not start basal insulin, and two-thirds of participants did not start rapid-acting insulin. Emotional distress did not appear to play a role in insulin initiation among trial participants
Successful treatment of recalcitrant amyopathic dermatomyositis with deucravacitinib in addition to intravenous immunoglobulin
No full textComparing the 2024 and 2017 Kawasaki Disease Statements From the American Heart Association
No full textTrends and disparities in motor vehicle collision injuries in Washington, D.C
No full textNonfatal traffic injuries are ~40 times more frequent than traffic fatalities in the United States, but little is known about racial or ethnic disparities in injury-only collisions because commonly used databases report racial/ethnic data only for fatalities. Crash data from police departments (e.g., Vision Zero) are subject to error and bias arising from changing patterns of police intervention and increased use of alternative or automated traffic enforcement. Here, we leverage Trauma Registry data to quantify racial/ethnic, temporal, and spatial patterns of trauma injuries from motor vehicle collisions among adults in Washington, D.C. and compare results to the commonly used Vision Zero database. We report results by year (2019-2023), road user type (motorists, pedestrians, cyclists, and other vulnerable road users), and ZIP code tabulation area (ZCTA) to identify primary contributors to total injury rates and racial/ethnic disparities. Between 2019 and 2023, the overall incidence rate (IR) rose from 69 to 132 per 100,000 persons per year and increased among all road user types and races/ethnicities. Compared to white people, the incidence rate ratio (IRR) was ≥4.3 among Black/African American people and ≥2.9 among Hispanic/Latino people. The IRR between Black/African American vs. white motorists is ≥9.9. Disparities were observed across 21 of 26 ZCTAs, revealing that disparities cannot be explained by solely by higher minority populations in ZCTAs with more hazardous infrastructure. The commonly used Vision Zero dashboard suggests a downward trend in injury-only crashes, but our analysis suggests that this trend is the result of a bias from reduced police intervention
Genitourinary syndrome of menopause (GSM): recommendations from the Fifth International Consultation on Sexual Medicine (ICSM 2024)
No full textINTRODUCTION: Genitourinary syndrome of menopause (GSM) encompasses a cluster of sexual symptoms like dyspareunia associated with genital and urinary symptoms like urinary urgency, which may be variably reported in the clinical setting. OBJECTIVES: To provide a comprehensive guide for healthcare professionals (HCPs) in sexual medicine, helping them effectively recognize and manage GSM, a very common chronic and progressive condition with an impact on quality of life and intimate relationships. METHODS: An expert committee, invited from seven countries by the 5th International Consultation on Sexual Medicine (ICSM), was comprised of eight researchers and clinicians with expertise in menopause medicine, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of GSM. RESULTS: Presence of at least one GSM symptom ranges from 14% to 87% in postmenopausal women, with vaginal dryness and dyspareunia being the two most common symptoms. A summary of the recommendations on GSM management deriving from the evaluation of data, subject to its quality published in the scientific literature, is provided. CONCLUSIONS: GSM is a relatively new disorder with an expanded definition to further the older long-recognized condition of vulvovaginal atrophy (VVA) in postmenopausal women to include urinary symptoms and anchor the disorder to menopause and the hypoestrogenic state. This new disorder has provided renewed incentives to formalize a significant amount of multidisciplinary research in the last decade. However, many areas ranging from epidemiology to tailored effective and safe treatment options in clinical practice still require in-depth additional investigations
Reply to the Letter to the Editor: The Role of Patient-Reported Symptoms in Standardizing MGFA Class 0 and MGFA-PIS
No full textBrodalumab as a Second-Line Therapy in Psoriasis: Rapid Response and Unique Mechanism of Action After Biologic Failure
No full textThis narrative review evaluates the clinical evidence supporting brodalumab as a second-line therapy against moderate-to-severe plaque psoriasis in adults who have experienced prior systemic treatment failure. Despite advances in biologic therapy, treatment failure remains a substantial challenge, with patients often discontinuing initial biologic treatment owing to inadequate response. Here, we analyzed data from clinical trials, real-world studies, and observational research examining brodalumab\u27s efficacy in treatment-experienced populations. Unlike other biologics that target specific interleukin 17 (IL-17) cytokines, brodalumab blocks the IL-17 receptor A and prevents signaling from multiple IL-17 family members, potentially explaining its effectiveness in treatment-resistant cases. The evidence presented here demonstrates rapid Psoriasis Area and Severity Index response rates, as well as durable efficacy of brodalumab in patients after a failed treatment with previous biologic therapies. This narrative review synthesizes the current evidence base for brodalumab\u27s role specifically in the second-line setting, providing clinicians with a comprehensive assessment of its efficacy in treatment-resistant psoriasis
Effectiveness of an Incentives-Enhanced Stepped Care Intervention Program in Diabetes Prevention in a Multiethnic Asian Prediabetes Cohort: Results From the Pre-DICTED Randomized Controlled Trial
No full textOBJECTIVE: Diabetes prevention in real-world settings is affected by the challenge of intervention adherence and difficulty in sustaining behavior change. This study evaluated the effectiveness of a stepped care prevention program, enhanced with financial incentives, in reducing the risk of diabetes conversion in a multiethnic prediabetes cohort in Singapore. RESEARCH DESIGN AND METHODS: The Pre-Diabetes Interventions and Continued Tracking to Ease Out Diabetes (Pre-DICTED) trial was a randomized controlled trial involving 751 overweight or obese individuals with impaired glucose tolerance, impaired fasting glucose, or both. Participants were assigned to standard care (control arm) or a stepped care intervention program, starting with lifestyle interventions for 6 months before adding metformin for participants who remained at high risk of diabetes conversion based on study visit assessments. Intervention arm participants also received financial incentives for attending lifestyle sessions and for achieving ≥5% weight loss. The primary end point was the proportion of participants developing diabetes at 3 years in the modified intention-to-treat population. RESULTS: After 3 years, 34.8% of participants in the intervention arm developed diabetes compared with 47.3% in the control arm (adjusted risk difference -10.93%; 95% CI -18.04 to -3.81; P = 0.003). The adjusted relative risk was 0.74 (95% CI 0.62-0.88; P \u3c 0.001). In the intervention arm, 26.4% of participants received metformin, and 45.1% received cash incentives. Adverse events were more common in the intervention arm, mainly because of metformin-related gastrointestinal symptoms. CONCLUSIONS: A stepped care diabetes prevention program, enhanced with financial incentives, effectively reduced diabetes conversion in a multiethnic Asian prediabetes cohort
Targeting the ARF6-dependent recycling pathway to alter lipid rafts and reduce inflammation
No full textPartitioning of inflammatory receptors into lipid rafts is essential for their function, making lipid rafts a promising target for anti-inflammatory therapies. However, the practical application of lipid raft-targeted therapies has been limited by a lack of mechanistic understanding of their regulation. In this study, we demonstrate that targeting the Arf6-dependent recycling pathway effectively modifies lipid rafts and mitigates inflammation. Using Oxy210, a synthetic oxysterol, we observed significant anti-inflammatory effects both in vivo and in vitro. These effects were linked to an increased abundance of ABCA1, enhanced cholesterol efflux, and alterations in the abundance and composition of lipid rafts. Mechanistically, Oxy210 disrupted the recycling checkpoint in late endosomes by reducing the abundance and activation of the small GTPase Arf6 and decreasing PI(4,5)P2 levels. This impaired lipid raft recycling to the cell surface and simultaneously reduced ABCA1 internalization. These findings highlight a novel approach to modulating lipid raft-dependent pathological pathways, with potential applications in treating inflammation, neurodegeneration, and infectious diseases
