Citations

Abstract Background: Pharmacogenomic studies on antidepressant treatment outcomes could be conducted using previously collected data from electronic health record (EHR)-linked biobanks. However, absence of EHR based outcome measures is an unmet need in designing such studies We aimed to define EHR-derived antidepressant outcome measures and explore their utility in showing associations between treatment outcomes and Cytochrome P450 (CYP) metabolizer phenotypes in a proof-of-concept study. Methods: Using data from the EHR-linked cohort, Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT 10K) Study, we collected prescription data and patient health questionnaire 9 (PHQ-9) scores to compute 3 proxy measures for antidepressant response, efficacy, and acceptability: change in PHQ-9 scores, longest treatment interval with a single antidepressant, and antidepressant non-refill. Subsequently, we tested the association of both prescription-based outcomes with DNA-predicted CYP metabolizer phenotypes in European-ancestry participants. Results: We identified 3920 RIGHT 10K participants with at least 1 antidepressant prescription and European-ancestry. Participants had a mean age of 61 years and 72% were women. Implementation of the PHQ-9 outcome was not feasible because of missingness. Of both prescription-based outcomes, antidepressant non-refill reproduced several known antidepressant-CYP interactions. However, the pilot was limited by small subgroups of participants with non-normal metabolizer phenotypes. Conclusions: Derived from structured data, antidepressant non-refill is a promising outcome measure for EHR-linked biobanks that partially reproduced antidepressant-CYP interactions. However, testing on larger datasets is necessary to understand whether it would be a useful for pharmacogenomic research.

AbstractChronic pelvic pain (CPP), a debilitating condition affecting an estimated 25% of women worldwide, represents a significant yet understudied global health crisis. Existing research is limited and likely fails to capture the true impact of CPP on global health. What is known is that CPP results in a profound health, societal, and economic burden on women. Our inability to fully understand this burden is a critical gap in women's healthcare. To address this urgent need, the International Federation of Gynecology and Obstetrics (FIGO) and the International Pelvic Pain Society (IPPS) have partnered to develop this consensus statement where we examine the key challenges to accessing CPP care and propose a framework for overcoming these barriers. We emphasize that effective global strategies for addressing the negative health consequences of living with CPP must prioritize the lived experiences of patients, empower healthcare professionals with the necessary tools and training, and drive meaningful policy change. This call to action is grounded in a comprehensive vision of women's health and rights to address the full spectrum of conditions women experience throughout their lives. Given its high prevalence, CPP must be a central focus of this expanded vision.

BACKGROUND AND OBJECTIVES: Rising US healthcare costs and the COVID-19 pandemic put increased pressure on hospitals to reduce patient length of stay (LOS) while maintaining high-quality care. We aimed to determine if implementing a pathway for same-day discharge after elective neuroendovascular procedures to a monitored hotel setting is safe, feasible, and cost-effective. METHODS: We evaluated patient outcomes after elective neuroendovascular procedures and same-day discharge to an on-campus Care Hotel. The study enrolled patients aged ≥18 years from October 1, 2020, to February 28, 2023. Exclusion criteria comprised major comorbidities, additional care necessitating hospitalization, absence of a caregiver, insurer-mandated hospitalization, or patient refusal of the Care Hotel model. Primary outcomes were readmission rate or prolonged LOS, new ischemic or hemorrhagic complications rate, and death rate from vascular causes within 6 months. Secondary outcomes included adverse events and deaths related to causes other than vascular complications within 6 months and changes in modified Rankin Scale score by 1 or more points at last follow-up. Healthcare cost savings associated with same-day discharge were analyzed using a control group. RESULTS: The study included 42 patients discharged to the Care Hotel and 84 controls. The average age was 61 years in the Care Hotel group and 64 years in the control group, and aneurysm treatment was the most frequent neuroendovascular procedure (83.3% and 79.8%, respectively). The readmission and extended LOS rates were 4.8% for the Care Hotel group. The rate of new ischemic or hemorrhagic complications was 4.8%. Cost analysis estimated savings of $7730.12 per procedure. CONCLUSION: This study suggests that the Care Hotel model is a safe, feasible, and cost-effective option for carefully selected patients undergoing elective neuroendovascular interventions. Adherence to discharge readiness criteria and meticulous patient selection are critical to minimizing complications and readmissions.

Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a “less severe condition” (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time. Methods: A multicenter retrospective cohort study (2009–2019) included patients with mAH (MELD score ≤20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis. Results: We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as a MELD score ≤20 at admission. Twenty-four percent met the criteria for an mAH episode. Patients with mAH tend to be older and have a higher proportion of females, with a median MELD of 17 (15–19), Maddrey discriminant function (mDF) of 33 (22–40), the trajectory of serum bilirubin of 0.83 (0.60–1.21), and neutrophil-to-lymphocyte ratio (NLR) of 5 (2.96–8.60). The primary causes of death in mAH included multiple organ failure (34.1%) and infections (16.6%). The cumulative survival rates at 30, 90, and 180 days were 94.3%, 90.4%, and 88.2%, respectively. In multivariable analysis, age was the only significant predictor of 30-day mortality (HR 1.49, 95% CI: 1.27–1.76, p <0.001). Mortality prediction models showed poor performance, with AUC for MELD (0.671), mDF (0.726), trajectory of serum bilirubin (0.733), and NLR (0.697). Conclusions: Patients with moderate AH exhibited a mortality of 11.8% at 6 months, primarily driven by multiple organ failure and infections. These patients also exhibit a different clinical profile compared to those with sAH. Tailored models and therapeutic strategies are needed to improve long-term outcomes in mAH.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Objective The objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis. Methods The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response. Conclusion This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Background: Anatomically accurate illustrations are imperative in medical education, serving as crucial tools to facilitate comprehension of complex anatomical structures. While traditional illustration methods involving human artists remain the gold standard, the rapid advancement of Generative Artificial Intelligence (GAI) models presents a new opportunity to automate and accelerate this process. This study evaluated the potential of GAI models to produce craniofacial anatomy illustrations for educational purposes. Methods: Four GAI models, including Midjourney v6.0, DALL-E 3, Gemini Ultra 1.0, and Stable Diffusion 2.0 were used to generate 736 images across multiple views of surface anatomy, bones, muscles, blood vessels, and nerves of the cranium in both oil painting and realistic photograph styles. Four reviewers evaluated the images for anatomical detail, aesthetic quality, usability, and cost-effectiveness. Inter-rater reliability analysis assessed evaluation consistency. Results: Midjourney v6.0 scored highest for aesthetic quality and cost-effectiveness, and DALL-E 3 performed best for anatomical detail and usability. The inter-rater reliability analysis demonstrated a high level of agreement among reviewers (ICC = 0.858, 95% CI). However, all models showed significant flaws in depicting crucial anatomical details such as foramina, suture lines, muscular origins/insertions, and neurovascular structures. These limitations were further characterized by abstract depictions, mixing of layers, shadowing, abnormal muscle arrangements, and labeling errors. Conclusions: These findings highlight GAI’s potential for rapidly creating craniofacial anatomy illustrations but also its current limitations due to inadequate training data and incomplete understanding of complex anatomy. Refining these models through precise training data and expert feedback is vital. Ethical considerations, such as potential biases, copyright challenges, and the risks of propagating inaccurate information, must also be carefully navigated. Further refinement of GAI models and ethical safeguards are essential for safe use.

Précis: Patients with clinically uncontrolled open angle glaucoma submitted to isolated gonioscopy-assisted transluminal trabeculotomy or combined with phacoemulsification not only achieved low mean IOPs, but also demonstrated stable IOP patterns during a 24-month follow-up. Purpose: To assess the impact of gonioscopy-assisted transluminal trabeculotomy (GATT) on long-term intraocular pressure (IOP) variation. Patients and Methods: An unicentric retrospective study including 169 consecutive patients who had undergone standalone GATT or combined with phacoemulsification (PHACOGATT) due to clinically uncontrolled open angle glaucoma, with at least 12 months of follow-up was conducted. Long-term mean IOP, long-term IOP peak, long-term IOP fluctuation, coefficient of variation, mean-positive IOP variation, sustained clinically significant positive IOP variation, and number of follow-up visits with IOP ≥15 mm Hg were investigated. Results: One hundred sixty-nine eyes from 169 patients were included (GATT group=101 patients; PHACOGATT group=68 patients). Mean long term IOP (12.0±1.8 vs. 11.2±2.0 mm Hg), mean long-term IOP peak (12.9±2.6 vs. 11.8±3.5 mm Hg), and mean coefficient of variation (0.07±0.08 vs. 0.05±0.09) were lower in the PHACOGATT group, while mean IOP fluctuation (1.0±3.7 vs. 1.2±1.8 mm Hg) was lower in the GATT group. In addition, the overall mean-positive IOP variation was 0.79±1.64 mm Hg. Finally, only 6.5% of the patients presented sustained clinically significant positive IOP variation and IOP was ≥15 mm Hg in 5.9% of the follow-up visits. Conclusions: Patients with clinically uncontrolled open angle glaucoma submitted to GATT or PHACOGATT achieved low mean IOPs and demonstrated stable IOP patterns. Our results provide additional evidence supporting GATT and PHACOGATT as viable options for the treatment of medically uncontrolled glaucoma patients requiring low and stable IOPs.

ABSTRACTBackgroundInsomnia and substance use disorders (SUD) are common comorbidities of bipolar disorder (BD). Genome‐wide association studies (GWAS) have uncovered shared genetic contributions to insomnia and BD as well as SUDs and BD. Electronic health record (EHR) derived phenotypes (phecodes) and questionnaire data were used to examine the relationship between insomnia genetic liability and SUDs in BD.Methods40,839 participants from the Mayo Clinic Bipolar Disorder Biobank (BD Biobank; n = 774) and Mayo Clinic Biobank (n = 485 BD cases, n = 39,580 controls) were included in the analyses of diagnosis (phecode) outcomes (insomnia, SUD, alcohol use disorder [AUD] and tobacco use disorder [TUD]). Analyses of specific SUD outcomes obtained through the BD Biobank questionnaire included 1789 cases and considered BD subtype. Logistic regression was used to test for associations between insomnia polygenic risk scores (PRS) and insomnia and SUD outcomes in BD cases and controls.ResultsInsomnia PRS was associated with having an insomnia diagnosis (phecode) in the EHR in controls (OR = 1.19, p = 9.64e‐33) but not in BD cases (OR = 1, p = 0.95). Associations between insomnia PRS and SUD diagnoses were significant in BD cases and controls, with the association being stronger in BD cases (interaction p = 0.024). In the BD Biobank data, the insomnia PRS was associated with increased odds of AUD (OR = 1.19, p = 4.26e‐04), TUD (OR = 1.21, p = 1.25e‐05) and cannabis use disorder (OR = 1.16, p = 4.19e‐03).ConclusionThe effect of genetic predisposition to insomnia on SUD risk may be stronger in BD cases than in controls, which could have clinical care implications for individuals with BD and comorbid SUD.