Deng, Yihong

Objective The aim of this study was to compare infection‐related hospitalization risk among patients with nonrenal systemic lupus erythematosus initiating commonly used immunosuppressants. Methods We emulated a target trial using Optum Labs Data Warehouse claims to compare the risk of infection‐related hospitalization among patients initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAAs) between March 2011 and September 2023. We excluded patients with prior lupus nephritis, solid‐organ or bone marrow transplantation, or rituximab/cyclophosphamide exposure. The primary outcome was time to first infection‐related hospitalization using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. We applied inverse probability of treatment weighting to account for baseline covariates and fitted marginal structural Cox models incorporating time‐varying monthly glucocorticoid dose during follow‐up. Results Among 6,168 patients, 24‐month cumulative incidence of infection‐related hospitalization was 10% (95% confidence interval [CI] 8–12) for azathioprine, 8% (95% CI 5–10) for belimumab, 10% (95% CI 8–11) for methotrexate, and 13% (95% CI 10–15) for MPAAs. In ITT analyses, MPAAs had higher risk than belimumab (hazard ratio [HR] 1.55, 95% CI 1.07–2.25) and methotrexate (HR 1.32, 95% CI 1.04–1.68). In PP analyses, azathioprine (HR 2.04, 95% CI 1.01–4.16) and MPAAs (HR 2.27, 95% CI 1.11–4.62) had higher risk compared with belimumab. After accounting for time‐varying monthly glucocorticoid dose, between‐treatment differences were no longer significant. Conclusion Initial differences in the infection‐related hospitalization risk were attenuated after accounting for time‐varying glucocorticoid exposure. These findings highlight glucocorticoid exposure as an important factor associated with serious infection risk while recognizing that postbaseline glucocorticoid use may reflect both evolving disease activity and a pathway through which therapies influence infection risk. image

Objective Systemic sclerosis (SSc) is an autoimmune disease marked by immune dysregulation, leading to progressive fibrosis and multiorgan dysfunction. Autologous hematopoietic cell transplantation (autoHCT) has demonstrated superiority over conventional immunosuppression in randomized trials yet remains underused in the United States. We report outcomes following implementation of autoHCT as a standard‐of‐care strategy at our institution. Methods We performed a retrospective analysis of consecutive patients with severe SSc undergoing autoHCT between April 1, 2020, and December 31, 2023. Eligibility required progressive disease despite standard immunosuppressive therapy. Primary endpoints were overall survival (OS) and event free survival (EFS). Secondary endpoints included cumulative incidence of relapse and nonrelapse mortality (NRM), organ‐specific outcomes, and transplant‐related complications. Results Twenty‐five patients underwent autoHCT. Median age was 46 years; 80% were female. At a median follow‐up of 23 (interquartile range 16.4–31.9) months, two‐year OS was 91.67% (95% confidence interval [CI] 81.25–100.0) and EFS was 74.51% (95% CI 58.78–94.45). Two‐year cumulative incidence of relapse was 23.93% (95% CI 4.27 –43.59), and NRM was 8.33% (95% CI 2.97–19.64). Significant improvement in Modified Rodnan Skin Score was observed at day +90 and +180 ( P < 0.05), whereas pulmonary function stabilized. Infectious complications occurred in 56% of patients, primarily viral reactivations. Conclusion Implementation of autoHCT for severe SSc in a multidisciplinary care model was associated with favorable survival and meaningful improvement in skin disease, with acceptable toxicity. Earlier referral and optimization of conditioning strategies may further reduce relapse and treatment‐related morbidity.

Importance The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RA) demands a better understanding of their association with thyroid cancer. Objective To estimate the risk of incident thyroid cancer among adults with type 2 diabetes being treated with GLP-1RA vs other common glucose-lowering medications. Design, Setting, and Participants This was a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study using claims data for enrollees in commercial, Medicare Advantage, and Medicare fee-for-service plans across the US. Eligible participants were adults with type 2 diabetes at moderate risk for cardiovascular disease and without history of thyroid cancer who had newly filled prescriptions for GLP-1RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), dipeptidyl peptidase-4 inhibitor (DPP4i), or sulfonylurea from January 1, 2014, to December 31, 2021. Data were analyzed February 1 to October 31, 2024. Main Outcomes and Measures Overall and piecewise (&amp;lt;1, 1-2, and ≥2 years since treatment initiation) hazard ratios (HRs) for thyroid cancer with use of GLP-1RA vs the other 3 drug classes were estimated using inverse propensity score weighted Cox proportional hazards models. Modified intention-to-treat (mITT) (primary) and as-treated (sensitivity) analyses were performed. Results Of 351 913 patients (mean [SD] age, 65.3 [8.5] years; 173 391 [49.3%] females and 178 522 [50.7%] males), 41 112 started treatment with GLP-1RA; 76 093, with DPP4i; 43 499, with SGLT2i; and 191 209, with sulfonylurea therapy. The numbers of patients diagnosed with thyroid cancer were 69 (0.17%) in the GLP-1RA group, 172 (0.23%) in the DPP4i group, 72 (0.17%) in the SGLT2i group, and 381 (0.20%) in the sulfonylurea group. In the mITT analysis, GLP-1RA initiation was not significantly associated with increased overall risk for thyroid cancer compared to the other 3 diabetes drugs (HR, 1.24; 95% CI, 0.88-1.76). However, the risk for thyroid cancer was significantly higher within the first year after GLP-1RA initiation (HR, 1.85; 95% CI, 1.11-3.08) and was amplified in the overall as-treated analysis that censored patients when therapy was discontinued or another medication was added (HR, 2.07; 95% CI, 1.10-3.95). Conclusions and Relevance This secondary analysis of a target trial emulation of a comparative effectiveness study found that despite the low absolute risk of thyroid cancer among patients receiving GLP-1RA therapy, there was an increased risk of new thyroid cancer diagnoses within the first year of GLP-1RA initiation compared to 3 other diabetes drugs. This finding may have been due to enhanced early detection; therefore, further research is necessary to understand the underlying causes of this association.

In this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium–glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously.

Introduction: Recently, an artificial intelligence (AI) algorithm was validated for identifying ECG signatures of atrial fibrillation (AF) risk during normal sinus rhythm. Traditionally, socioeconomically disadvantaged populations are less likely to receive novel or guideline-recommended treatments, and have high chronic disease burden, including cardiovascular diseases. There have also been concerns about new technologies creating a digital divide, worsening existing health disparities. Hypothesis: An AI algorithm will detect AF risk unequally across patients with different levels of social determinants of health (SDOH). Methods: The initial prospective, non-randomized, interventional study leveraged EHR and digital technologies to prospectively enroll 1004 patients with a broad range of AI-ECG risks of AF, who received continuous cardiac rhythm monitoring for up to 30 days. The Area Deprivation Index (ADI) was used as a composite measure of SDOH which is comprised of indicators spanning four domains: income, education, employment, and house quality. 904 intervention patients linked to the ADI data were matched to 904 real-world control patients derived from eligible but unenrolled patients. Those with ADI under 33% were defined as having better SODH; and patients with ADI above 33% were defined as having worse SODH. Results: Median age was 74 years and 38% were women. After matching, the intervention and control arms were balanced in all baseline characteristics, including HF, HTN, diabetes, stroke, CAD and ADI. A hazard ratio of 3.11 (P<0.001) was computed when comparing intervention to control for primary AF diagnosis outcome. In patients with worse SDOH, the intervention increased AF detection from 2.6% to 8.8% (HR 3.63 [2.09, 6.32]); in the better SDOH, the intervention increased AF detection from 3.9% to 9.3% (2.41 [1.23, 4.74]). Conclusions: An AI-guided AF screening program increased the detection of AF in both patients with better or worse SDOH. The current study validates the use of AI in historically disadvantaged populations displaying the possibility for broad implementation with decreased possibility of perpetuating disparities.