Ospina, Naykky Singh

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 Benign thyroid nodules (BTNs) are highly prevalent, and current treatment options are primarily invasive. There is a need for effective, noninvasive alternatives. Objective To systematically evaluate the efficacy of repurposed pharmacologic agents in reducing the size of BTNs. Data Sources MEDLINE, EMBASE, Cochrane databases, and Scopus were searched from inception to December 18, 2024. Study Selection We included preclinical and clinical studies evaluating repurposed drugs for BTNs in adults. Of 1499 records screened, 20 studies met inclusion criteria: 6 randomized controlled trials (RCTs), 6 prospective cohorts, 3 retrospective observational studies, 3 case reports, 1 cross-sectional study, and 1 preclinical study. Data Extraction Data were extracted independently in duplicate using a standardized form. Data Synthesis Narrative synthesis was conducted due to heterogeneity. Metformin was the most frequently evaluated agent (7 studies), with 5 studies (including 2 RCTs) reporting statistically significant reductions in dominant nodule volume. One prospective study demonstrated a reduction in the maximum nodule diameter, which was not statistically significant, and 1 RCT showed no changes in nodule size after intervention. Statins (4 studies) and somatostatin analogues (4 studies) showed mixed results. Myo-inositol with selenium, herbal formulations, and immune checkpoint inhibitors showed promise in single studies or case reports. Conclusion Metformin shows the most consistent potential for noninvasive reduction of BTN size, particularly in patients with metabolic comorbidities. However, current evidence is limited and heterogeneous. Further large-scale studies are needed to confirm efficacy and guide clinical use.

Abstract Context Thyroid nodules are common in clinical practice, and inappropriate selection of patients for thyroid biopsy can contribute to thyroid cancer overdiagnosis or delayed diagnosis. Objective This work aimed to evaluate the frequency of inappropriate thyroid biopsies in practice, following a framework that integrates thyroid nodule ultrasound (US) features and patient-specific clinical factors. Methods This cross-sectional study was conducted at a single academic center in the United States. Participants included adult patients who underwent their first thyroid fine-needle aspiration (FNA) biopsy between January 1, 2016, and December 31, 2023, at the University of Florida. Data collection included thyroid US characteristics, clinical factors (eg, comorbidities, patient preferences), and context for biopsy decision-making. Main outcome measures included the appropriateness of thyroid biopsy assessed using a tiered framework incorporating US features and additional clinical factors. Results A total of 899 patients were evaluated, with 441 meeting the inclusion criteria and undergoing 481 thyroid biopsies. Of these, 388 of 481 (80.7%) were classified as likely appropriate (L-APP) based on the American College of Radiology Thyroid Imaging Reporting and Data System criteria. In 34 of 481 (7%) of cases, clinical factors such as thyroid cancer risk features, comorbidities, symptoms, or patient preferences led to reclassification from likely inappropriate (L-INAP) to L-APP. In 50 of 481 (10%) of cases, limited life expectancy (eg, chemotherapy, end-stage disease) led to reclassification from L-APP to possibly or extremely inappropriate (EXT-INAP). EXT-INAP biopsies occurred in only 0.8% (4/481) of cases. Conclusion This study underscores the value of integrating US findings with clinical context to guide thyroid biopsy decisions and enhance patient-centered care.

Abstract Purpose Overuse of thyroid ultrasound (TUS) has contributed to rising thyroid cancer diagnoses and is projected to increase US healthcare costs from $1.5 billion to $3.5 billion by 2030. This study evaluated the healthcare cost of inappropriately ordered TUS in a national multicenter academic system. Methods This is a secondary cost analysis of a retrospective cohort study across 4 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ; and the Midwest Mayo Clinic Health System). Adult patients (≥18 years) undergoing their first TUS between January 1, 2017, and December 31, 2021, with at least 1 year of follow-up were included. TUS indications were classified as appropriate or inappropriate using a guideline-based natural language processing algorithm. The primary outcome was a comparison of adjusted 1-year all-cause healthcare costs. A secondary analysis calculated the direct procedural costs of the inappropriate TUS cascade. Results Among 6984 patients (mean age 56 [SD 16.4]; 76.2% female; 90.9% White), 546 (7.8%) underwent TUS for inappropriate indications. These patients were younger (mean age 53.0 vs 56.3 years, P < .0001) but otherwise demographically similar. Adjusted total healthcare costs over 90 days and 1 year were comparable: $4842 vs $5794 and $13 748 vs $14 257 for inappropriate vs appropriate TUS, respectively. The inappropriate TUS cascade, including an estimated 56 subsequent biopsies and 22 thyroidectomies, resulted in a minimum of $576 134 in direct procedural costs. Conclusion While adjusted total costs were similar, inappropriate TUS represents potentially avoidable spending and remains a viable target for cost-reduction strategies. Reducing low-value imaging remains a critical target for cost-saving interventions.

ImportanceThyroid cancer incidence has tripled in the past 3 decades, largely driven by increased detection of small, indolent papillary thyroid cancers. Overuse of thyroid ultrasonography (TUS) contributes to overdiagnosis, leading to unnecessary biopsies, procedures, and potential patient harm.ObjectiveTo evaluate the frequency of and factors associated with inappropriate TUS (iTUS) orders and assess related clinical outcomes.Design, Setting, and ParticipantsThis retrospective cohort study analyzed adult patients 18 years and older who underwent their first TUS from January 1, 2017, to December 30, 2021, at 4 Mayo Clinic sites. Patients with previous thyroid nodule, thyroid cancer, thyroid surgery, or TUS were excluded. Based on documented clinical indications, a validated natural language processing model classified TUS orders as appropriate or inappropriate. Data were analyzed from April 2024 to May 2025.ExposuresBaseline characteristics of patients, clinicians, and clinical encounters investigated for their association with an iTUS order.Main Outcomes and MeasuresThe primary outcome was the proportion of iTUS orders. Secondary outcomes included factors associated with iTUS (sociodemographic, clinical, order-specific, and clinician-related factors) and clinical outcomes following iTUS, including the detection of thyroid nodules, thyroid procedures, and thyroid cancer diagnoses.ResultsOf 11 442 included patients, 8422 (73.6%) were female, and the mean (SD) age was 57.3 (15.8) years with a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 29.7 (7.0). Among 11 442 TUS orders, 866 (7.6%) were classified as inappropriate. In multivariable analysis, younger age (age of 18 to 54 years vs older than 65 years; odds ratio [OR], 1.86; 95% CI, 1.56-2.22), hyperthyroidism (OR, 9.04; 95% CI, 6.75-12.11), ordering by nonendocrinology specialties (eg, oncology/hematology; OR, 3.43; 95% CI, 2.47-4.76), and orders not linked to an in-person appointment (eg, portal messages; OR, 2.42; 95% CI, 2.08-2.82) were strongly associated with increased odds of iTUS. Compared with appropriate TUS, iTUS led to lower rates of thyroid nodule detection (202 of 866 [23.3%] vs 6885 of 10 576 [65.1%]; OR, 0.16; 95% CI, 0.14-0.19), biopsies (89 [10.3%] vs 2647 [25.0%]; OR, 0.34; 95% CI, 0.27-0.43), partial thyroidectomies (14 [1.6%] vs 424 [4.0%]; OR, 0.39; 95% CI, 0.23-0.67), and confirmed thyroid cancer cases (16 [1.8%] vs 425 [4.0%]; OR, 0.45; 95% CI, 0.27-0.74).Conclusions and RelevanceIn this cohort study, approximately 1 in 13 TUS orders were inappropriate. iTUS was more common in younger patients, those with thyroid dysfunction, those not seen in person, and in those referred by nonendocrinology specialties. These findings highlight the need for targeted strategies to optimize TUS use and mitigate overdiagnosis and overtreatment.

ImportanceSurvivors of thyroid cancer represent 10% of all cancer survivors in the US, yet their unmet care needs remain unexplored. Understanding the unmet care needs of survivors of thyroid cancer could help develop targeted interventions to enhance their quality of life and overall well-being.ObjectiveTo summarize the unmet care needs of survivors of thyroid cancer and programs to address them and to summarize the reporting and patterns of sociodemographic factors influencing these needs across studies.Evidence ReviewA systematic review and meta-narrative synthesis on studies published from January 2000 to September 2023 that evaluated the unmet needs of survivors of thyroid cancer or clinical programs to address them. The review included quantitative, qualitative, and mixed-methods studies. Two reviewers independently identified relevant articles and extracted data using standardized forms. Unmet care needs were summarized using the Supportive Care Framework for Cancer, whereas sociodemographic characteristics were evaluated according to the PROGRESS-Plus framework. A narrative synthesis was performed for quantitative studies, and a meta-narrative was created for qualitative studies. The risk of bias in the included studies was also assessed.FindingsWe included 14 quantitative studies (n = 8930) and 9 qualitative studies (n = 166) evaluating unmet care needs. Reported participant demographics were female (7653/9034 [85%]), White (2497/2986 [84%]), 40 years or older (2497/2986 [58%]), well-educated (1493/2124 [70%]), married or in stable relationships (1445/2114 [68%]), and English-speaking (1815/1915 [95%]). Quantitative studies primarily assessed and demonstrated unmet psychological and informational needs among survivors of thyroid cancer. Qualitative synthesis highlighted the negative impact of thyroid cancer’s perception as a “good cancer,” unmet informational and emotional support needs throughout survivorship stages, and practical hindrances in daily life. Sociodemographic data reporting was limited to a few factors influencing thyroid cancer care (eg, age, sex reported in >90% vs socioeconomic status <10%). One interventional study evaluating a patient navigation program was identified.Conclusions and RelevanceThis systematic review found that adult survivors of thyroid cancer report unmet informational, psychological, emotional, and practical support needs, which may be influenced by the good cancer label. Although patient demographics shape thyroid cancer care experiences and needs, population description is primarily limited to age and sex, overlooking other important variables that can affect care.

Abstract Background Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. Objective To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. Methods The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. Results In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations. In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC—including contraception as a key component—showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception. In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy. In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition. In individuals with PDM, we suggest either a carbohydrate-restricted diet (<175 g/day) or usual diet (>175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day. In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM. In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target <140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting <95 mg/dL (5.3 mmol/L), 1-hour postprandial <140 mg/dL (7.8 mmol/L), and 2-hour postprandial < 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose > 126 mg/dL (7 mmol/L). In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI −4.24 to 11.86) and reduced time below range (MD −0.88%; 95% CI: −2.04 to 0.27) with the use of hybrid closed-loop pump technology. In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing. In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. Conclusion The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

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 (<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.

Abstract Objectives Diagnostic reconciliation is the collaborative process between patients and clinicians to create and reconcile evidence-based, feasible, and desirable care plans. However, the specific components of this process remain unclear. The objective of this study was to develop the first comprehensive framework to elucidate the diagnostic reconciliation process. Methods We followed a multi-step and iterative approach to develop the framework, including a focused systematic review of diagnostic conversations, quantitative evaluation of recordings of real-life clinical visits recordings, and stakeholder engagement (e.g., patients, clinicians, researchers). Results We identified 17 potential components to the process of diagnostic reconciliation through literature review and stakeholder engagement. After review of 56 clinical visits and further stakeholder engagement, we developed a final framework including four categories: 1) understanding the need for a test/referral, 2) logistics of test/referral scheduling, 3) test/referral information, and 4) test/referral results. Conclusions The proposed framework lays the foundation for evaluation and improvement of diagnostic conversations in practice. Clinicians can enhance patient-centered diagnosis by co-creating diagnostic plans of care in practice and using the components described in the novel diagnostic reconciliation framework.