Brito, Juan P.

Abstract Context. Thyroid nodule ultrasound findings are crucial in guiding management decisions for patients with thyroid nodules. However, the frequency with which ultrasound images are discussed and reviewed with patients during clinical visits is not well understood. Objective. To assess how often thyroid ultrasound images are shown and discussed with patients during consultations, and to identify predictors of image review during clinical visits. Design and setting. Secondary analysis of a multicenter pilot randomized clinical trial conducted at two academic medical centers in the United States. Participants. Adults undergoing evaluation for thyroid nodules. Intervention. Participants were randomized to receive either usual care or care enhanced with a conversation aid. Main Outcome Measures. The primary outcome was the frequency of thyroid nodule imaging review evaluated as a binary outcome. Secondary outcomes included evaluation of predictors of image discussion. Results. Eighty-five patients were evaluated. Most participants were women (80%), mean age (60 years, SD 16), and White (86%), undergoing new patient visits (84%). Thyroid nodule ultrasound images were reviewed with patients in 53% of visits (45/85), and in all cases, clinicians initiated the imaging discussion. Predictors of image review included type of consultation (new patient visit) (OR 10.6, 95% CI: 1.79, 62.3). Age, sex, study arm, thyroid nodule size or cancer risk and plan of care (e.g., completing a biopsy) were not statistically associated with review of clinical images. Conclusions. Review of thyroid ultrasound images during clinical visits is relatively common, with consultation type serving as significant predictor.

ABSTRACT Objective Women carry disproportionate shares of caregiving and other life demands that may compound the work of diabetes self-management. We sought to examine gender differences in overall and digital treatment burden and their key contributors. Research Design and Methods Cross-sectional analysis of two cohorts of adults with type 1 or type 2 diabetes attending outpatient endocrinology visits who completed the Treatment Burden Questionnaire Plus Digital (TBQ+D) (n=472). Multivariable regression estimated gender differences in overall and digital treatment burden, ability to live a normal life, and sustainability of current self- care effort, adjusting for age, diabetes type, insulin intensity, HbA1c, and cohort. Item-level analyses identified contributors to observed differences. Results Compared to men, women reported higher median overall treatment burden (33 vs 20, adjusted mean difference 10.6 points, 95% CI 5.1–16.3; p <.0001) and digital treatment burden (13 vs 7, adjusted mean difference 3.5 points, 95% CI 1.1–6.1; p =.009). They also had higher odds of not living a normal life (OR 1.77, 95% CI 1.18–2.67; p =0.006) and difficulty sustaining current self-care efforts indefinitely (OR 2.01, 95% CI 1.10–3.66; p =0.023). Digital burden differences were concentrated in annoyance, precautions, and time and effort required to use digital medicine tools, whereas contributors to differences in overall burden varied, with relationships, self-monitoring, and injections contributing most. Conclusions After adjusting for treatment intensity and other factors, women living with diabetes were twice as likely to be overwhelmed by diabetes care than men. Their greater vulnerability to treatment burden demands healthcare service redesign and individualization of plans of care that minimally disrupt patients’ and caregivers’ lives. ARTICLE HIGHLIGHTS Why did we undertake this study? Women may experience greater treatment burden across chronic conditions, reflecting competing (caregiving) demands that reduce capacity for self-management. Gender differences in diabetes, especially digital burden, remain unclear. What is the specific question we wanted to answer? Do women with diabetes experience greater overall and digital treatment burden than men? What did we find? Women reported greater overall and digital burden and more difficulty living a normal life and sustaining care than men. Differences were larger for digital annoyance, precautions, and effort, plus relationships, self-monitoring, and injections. What are the implications? Treatment burden cannot be inferred from treatment intensity alone. Diabetes care should consider whether treatment work fits within each patient’s life and can be sustained. Women with diabetes may be particularly vulnerable to becoming overwhelmed by the work of diabetes care.

Importance Primary hyperparathyroidism (PHPT) is common and contributes to skeletal and kidney end-organ damage. Although parathyroidectomy can mitigate these complications, many patients are managed with observation, and real-world data on the population-based frequency and timing of end-organ damage under usual care are limited. Objective To evaluate the frequency and timing of end-organ damage associated with PHPT. Design, Setting, and Participants This cohort study included a population-based cohort identified from national electronic health record (EHR) and claims data (2010-2023) with follow-up through 2023. Participants were adults with a new biochemical diagnosis of PHPT. Data analysis was performed from August 2025 to April 2026. Exposure A new biochemical diagnosis of PHPT was defined as an elevated PTH (&amp;gt;65 pg/mL) within 1 month after a second elevated calcium level (serum calcium &amp;gt;10.2 mg/dL or ionized calcium &amp;gt;1.3 mmol/L or &amp;gt;5.3 mg/dL). Main Outcomes and Measures PHPT-associated end-organ damage (osteoporosis, atraumatic fractures, kidney stones, stage 3 or worse chronic kidney disease) at or after PHPT diagnosis using EHR or claim codes and laboratory data, in addition to the frequency and timing of parathyroidectomy. Results A total of 43 399 patients with PHPT were identified (mean [SD] age, 67.9 [12.5] years; 33 854 [78%] female and 9545 [22%] male), of whom 22 279 (51.3%) had end-organ damage at diagnosis. Among 21 120 patients without end-organ damage at diagnosis, 6762 (32.0%) progressed to end-organ damage after a median (IQR) 516 (166-1125) days. Only 4442 patients (19.9%) with end-organ damage at diagnosis were treated with parathyroidectomy. Among those who progressed to end-organ damage, 1348 (19.9%) underwent subsequent parathyroidectomy, which occurred a median (IQR) 154 (41-439) days later. Conclusions and Relevance In this national cohort of adults with a biochemical diagnosis of PHPT, 67% had PHPT-associated end-organ damage at diagnosis or on follow-up. Despite this, parathyroidectomy was uncommon. These findings may inform strategies to optimize utilization of parathyroidectomy and mitigate PHPT-associated morbidity.

OBJECTIVE To examine kidney disease outcomes associated with dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH DESIGN AND METHODS In this target trial emulation, claims data from enrollees in commercial, Medicare Advantage, and traditional Medicare health plans were used to identify adults ≥21 years old with type 2 diabetes, with moderate cardiovascular risk, and without stage 3 or worse chronic kidney disease (CKD) initiating alogliptin, linagliptin, saxagliptin, or sitagliptin between 2014 and 2021. The primary outcome was a composite of incident CKD stages 3–5, kidney failure, or kidney replacement therapy. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method and incorporated as inverse probability of treatment weights into proportional hazards models. RESULTS The weighted study cohort included 3,026 individuals starting alogliptin, 38,213 starting linagliptin, 14,934 starting saxagliptin, and 115,091 starting sitagliptin. One year after treatment initiation, the primary outcome occurred in 1.4%, 2.7%, 2.2%, and 2.4% of patients initiating alogliptin, linagliptin, saxagliptin, and sitagliptin, respectively, increasing to 3.2%, 6.2%, 5.0%, and 5.4%, respectively, at 3 years. Alogliptin was associated with lower risk of stage 3 or worse CKD than linagliptin (hazard ratio [HR] 0.50; 95% CI 0.37–0.69), saxagliptin (HR 0.63; 95% CI 0.45–0.86), and sitagliptin (HR 0.58; 95% CI 0.42–0.79), while saxagliptin was associated with lower risk than linagliptin (HR 0.80; 95% CI 0.73–0.87). Conversely, linagliptin was associated with higher risk than sitagliptin (HR 1.15, 95% CI 1.10–1.21). CONCLUSIONS Alogliptin was associated with lower risk of moderate-to-severe kidney disease than other DPP-4i, while linagliptin was associated with higher risk. Limitations include lack of laboratory data and potential unmeasured confounding.

Introduction To assess the within-class variation in kidney outcomes following initiation of sulfonylurea therapy. Research design and methods We used claims data of enrollees in commercial, Medicare Advantage, and traditional Medicare health plans between 2014 and 2021 to emulate a target trial including adults ≥21 years with type 2 diabetes at moderate cardiovascular risk to compare initiation of glimepiride, glipizide, or glyburide on the incidence of chronic kidney disease (CKD) stage 3 or worse, including initiation of kidney replacement therapy (primary outcome); secondary outcomes examined incident CKD stages 3-4, kidney failure (including kidney replacement therapy), all-cause mortality, and hypoglycemia requiring emergency department or hospital care. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method, and incorporated as inverse probability of treatment weights into proportional hazards models. Results The weighted study cohort included 295 092 individuals starting glimepiride (n=134 926), glipizide (n=145 984), and glyburide (n=14 182). One year after treatment initiation, stage 3 or worse CKD developed in 2.1% of patients in the glimepiride group, 2.2% in the glipizide group, and 1.8% in the glyburide group. Glyburide was associated with a lower risk of kidney complications compared with both glimepiride (HR 0.84, 95% CI 0.76 to 0.92) and glipizide (HR 0.81, 95% CI 0.73 to 0.89), despite a higher risk of severe hypoglycemia (HR 1.47, 95% CI 1.27 to 1.71 vs glipizide and HR 1.22, 95% CI 1.05 to 1.42 vs glimepiride). In contrast, the risk of kidney complications was modestly increased with glipizide compared with glimepiride use (HR 1.04, 95% CI 1.00 to 1.07). Conclusions Glyburide was associated with a modestly lower risk of kidney complications, despite a higher risk of hypoglycemia, while glipizide was associated with a higher risk of kidney complications. These hypothesis-generating findings suggest important within-class differences that warrant consideration in clinical decision-making and future research. Despite rigorous prespecified causal inference analytic methods, the risk of unmeasured confounding and bias by indication with the use of observational data remains. Trial registration number NCT05214573 .

Background SGLT2 (sodium‐glucose cotransporter 2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetes. However, no direct comparison of individual SGLT2 inhibitor drugs has been conducted, particularly among adults with moderate cardiovascular risk who comprise most people with type 2 diabetes. Methods We used data for commercial, Medicare Advantage, and Medicare fee‐for‐service beneficiaries to emulate a target trial of adults (≥21 years) with type 2 diabetes and moderate cardiovascular risk who started canagliflozin, dapagliflozin, or empagliflozin between 2015 and 2020. We estimated propensity scores using the super learner ensemble method and incorporated them as inverse probability of treatment weights into Cox models, estimating risk of MACE, expanded MACE, and hyperglycemic and hypoglycemic crises through December 31, 2022. Results The weighted cohort, balanced on all baseline covariates, included 137 232 patients (mean age 65.7 years [SD, 8.1], 75.3% non‐Hispanic White, 57.0% male, 81.9% on metformin, 11.4% on glucagon‐like peptide‐1 receptor agonists) starting canagliflozin (N=42 877), dapagliflozin (N=17 871), or empagliflozin (N=7648). The risk of MACE was lower among patients starting empagliflozin versus canagliflozin (hazard ratio [HR], 0.92 [95% CI, 0.87–0.97]), driven by reduced risk of all‐cause mortality (HR, 0.86 [95% CI, 0.80–0.94]). There was no difference in MACE between empagliflozin versus dapagliflozin or dapagliflozin versus canagliflozin therapy. There was no difference in remaining outcomes between the three drugs. Conclusions The 3 most used SGLT2 inhibitor medications demonstrate similar effectiveness on cardiovascular outcomes among patients with type 2 diabetes at moderate cardiovascular risk, with differences between these drugs small in magnitude. Clinicians and health systems should prioritize enhancing access to these cardioprotective therapies.

Abstract Context Incidental thyroid findings (ITFs) are increasingly detected on imaging performed for non-thyroid indications. Their prevalence, features, and consequences remain undefined. Objective To develop, validate, and deploy a natural language processing (NLP) pipeline to identify ITFs in radiology reports and assess their prevalence, features, and clinical outcomes. Design Retrospective cohort study. Setting Mayo Clinic sites (Rochester, Arizona, Florida, Mayo Clinic Health System). Participants Adults without prior thyroid disease undergoing thyroid-capturing imaging from July 1, 2017, to September 30, 2023. A transformer-based NLP pipeline identified ITFs and extracted nodule characteristics from image reports from multiple modalities and body regions. Outcomes ITF prevalence, downstream thyroid ultrasound, biopsy, thyroidectomy, and cancer diagnosis. Logistic regression identified demographic and imaging-related factors. Results Among 115 683 patients (mean age, 56.8 [SD 17.2]; 52.9% women), 9077 (7.8%) had an ITF (92.9% nodular). ITFs were more likely in women, older adults, higher BMI, and in imaging ordered by specialties different from Emergency Medicine. Compared with chest CT, ITFs were more likely via neck CT, PET, and nuclear medicine scans. Nodule characteristics were poorly documented, with size reported in 44% and other features in fewer than 15%. Compared with patients without ITFs, those with ITFs had higher odds of thyroid nodule diagnosis (OR 45, 95%CI 41.1-49.3), biopsy (OR 46.8, 95%CI 39.0-56.2) thyroidectomy (OR 55.8, 95%CI 31.3-99.3), and thyroid cancer diagnosis (OR 61.7, 95%CI 38.6-98.5). Most cancers were papillary (88.5%) and larger when detected after ITFs (2 cm SD 1.4) vs no ITF (1.3 cm SD 0.8). Conclusion ITFs were common and strongly associated with cascades leading to the detection of small, low-risk cancers, highlighting their role in overdiagnosis and the need for standardized reporting and more selective follow-up.

Abstract Context Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity and can lead to substantial weight loss. In patients taking levothyroxine, weight loss can reduce thyroid hormone requirements and potentially associated adverse effects. Thyroid-stimulating hormone (TSH) monitoring is essential but unclear whether thyroid function is routinely reassessed after GLP-1 RAs initiation. Objective Examine the changes in the timing of TSH testing after GLP-1 RAs. Design Retrospective cohort study emulating a target trial using Medicare from January 1, 2011, to December 31, 2020. The primary analysis followed an intention-to-treat approach. Patients were matched 1:1 using propensity scores. Logistic regression models and informed by least absolute shrinkage operator variable selection were used. Setting The 15% sample of U.S. Medicare fee-for-service claims data. Patients or Other Participants Adults aged ≥65 years with type 2 diabetes on a stable levothyroxine dose at baseline. Intervention(s) Initiation of GLP-1 RAs vs initiation/ongoing use of sodium-glucose cotransporter-2 inhibitors (SGLT-2is). Main Outcome Measure(s) TSH testing during follow-up. Results Among 5370 matched patients, the mean age was 73.2 years. 71.6% were women, and 87.1% were White. Approximately 83.0% of patients in both treatment groups receive a TSH testing within a 1-year follow-up. The mean time to TSH testing was approximately 130.5 days for both groups. Conclusion TSH testing patterns did not differ between GLP-1 RAs and SGLT-2is, despite the greater likelihood of requiring levothyroxine dose adjustment associated with weight loss seen with GLP-1 RA therapy. Given levothyroxine's widespread use, this gap suggests missed opportunities for timely and weight-responsive thyroid monitoring.