Montori, Víctor M.

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 Objective To evaluate the effectiveness of multiple decision aid strategies in promoting high quality shared decision making for prevention of stroke in patients with non-valvular atrial fibrillation. Design Cluster randomized controlled trial. Setting Six academic medical centers in the United States. Participants Patient participants were aged ≥18 with a diagnosis of non-valvular atrial fibrillation, at risk for stroke (CHA 2 DS 2 -VASc ≥1 for men, ≥2 for women), and scheduled for a clinical appointment to discuss stroke prevention strategies. Participating clinicians were those who manage stroke prevention strategies for participating patients. Intervention Patients were randomized to use a patient decision aid or usual care; clinicians were randomized to use an encounter decision aid or usual care with all participating patients. Main outcome measures Primary outcome measures were quality of shared decision making measured by OPTION12, knowledge of atrial fibrillation and its management, and decisional conflict. Results 1117 participants across six sites were included in the analysis. Compared with usual care, the combined use of both the patient decision aid and the encounter decision aid improved the quality of shared decision making (adjusted mean difference 12.1 (95% confidence interval (CI) 8.0 to 16.2; P<0.001), improved patients’ knowledge (odds ratio 1.68 (95% CI 1.35 to 2.09; P<0.001), and reduced patients’ decisional conflict (adjusted mean difference −6.3 (95% CI −9.6 to −3.1; P<0.001). Statistically significant improvements were also observed with the encounter decision aid alone versus usual care for all three outcomes and with the patient decision aid alone versus usual care for quality of shared decision making and knowledge. No important differences were observed in treatment choices for stroke prevention or in participants’ satisfaction. No statistically significant difference in the length of visit across study groups was detected. Conclusion Patients who received any decision aid (encounter decision aid, patient decision aid, or both) had lower decisional conflict, better shared decision making, and greater knowledge than those receiving no decision aid, except for the effect of the patient decision aid on decisional conflict, which did not reach statistical significance. The study establishes that use of either pre-visit or in-visit decision aids individually or in combination is advantageous compared with usual care. Trial registration ClinicalTrials.gov NCT04357288 .

Abstract The demands associated with ongoing disease management may overwhelm middle aged and older adults living with two or more chronic conditions. Treatment burden refers to both (a) the numerous demands—such as the time and costs of travel to clinical appointment, administrative burden, and coordinating fragmented care—healthcare makes on patients and (b) the negative impact on the patient’s wellbeing. We evaluated data from respondents of the treatment burden experimental module included in the 2022 Health and Retirement Study data collection wave (N=1,888). We analyzed responses to the 15-item Treatment Burden Questionnaire (TBQ; 15 questions scored 0-10; total sum 0-150; &gt;59 considered unsustainable burden). We compared mean total TBQ score by sociodemographic and multimorbidity combination groups using either a t-test (among 2 groups) or ANOVA (among &gt;2 groups). We compared sustainability across groups using a chi-square test. Respondents (mean 69 years; 62% female, 71% living with 2+ chronic conditions) had a mean TBQ score of 20.3/150 (SD 22.7) with 125 (6.6%) reporting unsustainable burden. Administrative and financial tasks and lifestyle changes were the most burdensome activities. Unsustainable burden was significantly more likely among younger (51-64 vs. older), lower educated (&lt; high school vs. ≥high school), and Black and Latino (vs. non-Latino White) respondents, and in those living with 2+ chronic conditions. In this nationally-representative sample of US adults, participants reported less treatment burden than previously reported in international studies. Certain sociodemographic groups reported high and unsustainable burden of treatment, informing future interventions to reduce treatment burden in mid and late life.

Objective Patients with heart failure (HF) perform a variety of self-care activities to control symptoms and minimise the risk of HF decompensations. The objective of this study was to understand how patients build capacity and manage the work of living with HF. Design A qualitative study using semi-structured telephone interviews. The interview guide was informed by the Cumulative Complexity Model, a conceptual framework that focuses on a patient’s workload and their capacity to manage that work. Interview transcripts were analysed using a mixed inductive and deductive coding approach with organisation into larger thematic categories. Setting Southeastern Minnesota USA (11 counties) with capture of data from local community healthcare providers under the auspices of the Rochester Epidemiology Project. Participants Intentional sampling of local patients with HF (n=24, median age 69.5 years, 54% women, 63% rural, 54% preserved ejection fraction) who reported high treatment burden and/ or poor health status on a questionnaire. Results Three major themes emerged: using capacity to manage workload, disruptions resulting in workload exceeding capacity and regaining workload-capacity balance. Participants described routinising the daily tasks associated with living with HF to minimise the associated burden and identified disruptions to their routines, including hospitalisations, emergency room visits, worsening health status and changes in healthcare access. To accommodate disruptions and regain workload-capacity balance, participants decreased workload and/or transferred tasks to others to maximise capacity. Conclusions Participants with HF described managing patient workload in times of stable health, but they sometimes struggled to accommodate disruptions and worsening health status. These findings can inform the design of interventions to minimise workload, maximise capacity and improve quality of life for patients with HF.

Abstract Introduction: Patient and stakeholder involvement enhances the conduct and applicability of comparative effectiveness research (CER). However, examples of engagement practices for CER leveraging real-world data (i.e., data from routine clinical practice) are scarce. Notably, these studies differ from traditional clinical trials in their technical complexity and minimal prospective data collection, posing unique challenges for stakeholder involvement. This paper describes patient and stakeholder engagement in a CER study of type 2 diabetes (T2D) medications using real-world data from a large administrative claims database. Methods: A Patient and Stakeholder Advisory Group (PSAG) was formed to guide study design, conduct, and dissemination. The PSAG (n = 12) included individuals with T2D, clinicians, health systems leaders, professional society representatives, and a payer representative. Members were surveyed post-study initiation to assess their participation goals and experiences to date. Results: PSAG members influenced key design and methodological decisions, including cohort selection and adding an aim focused on patient preference elicitation. Survey results indicated high satisfaction with engagement processes and a desire for ongoing involvement. Most PSAG members cited their main goals as impacting the lives of people with T2D and ensuring the research’s relevance to clinicians. Conclusions: Best practices for engaging stakeholders in CER using real-world data are underdeveloped. Our experience suggests that an inclusive, stakeholder-engaged approach enriches the research process and ensures diverse perspectives are integrated into study design and conduct. Ongoing efforts will focus on assessing long-term engagement outcomes and PSAG member satisfaction.

Background: Guidelines recommend shared decision-making (SDM) for patients with atrial fibrillation (AF) making decisions regarding anticoagulation for stroke prevention. Decision support tools (e.g., Decision Aids [DAs]) facilitate SDM. However, little research has compared the effectiveness of the two most common types of DAs: (1) encounter decision aid (EDA) and (2) pre-encounter patient decision aid (PDA). Our study assessed the comparative effectiveness of PDAs and EDAs on SDM during AF clinical encounters where stroke prevention strategies were discussed. Research Question: Do decision aids (PDA or EDA), alone or in combination, improve patients’ AF decision-making experience compared to usual care? Methods: A cluster randomized multi-center trial in patients with AF comparing usual care (no DA) vs. one DA (EDA or PDA) or both DAs. Clinicians and patients were randomized independently into 4 study arms. Clinicians were randomized to use or not use the EDA for all study visits, and patients were randomized to use or not use the PDA. Co-primary outcome domains were: (1) quality of SDM (2) patient knowledge, and (3) decisional conflict. Secondary outcomes included: (1) treatment choice, (2) treatment initiation, and (3) treatment persistence. Patient characteristics were assessed. We will present comparisons of the randomized DAs on the co-primary and secondary outcomes and subgroup analyses. Results: Between December 2020-July 2023, investigators in 6 U.S. healthcare systems enrolled 1117 patients (mean (M) age 69, 63% male, 89% White) and 107 clinicians. Compared to usual care (no DA, M=31.6), SDM was better in patients receiving PDA (M=35.4) and EDA (44.5) alone or together (M=43.7; p’s<0.001). Knowledge about AF was greatest for those receiving both DAs or the PDA alone (84% accurate responses for PDA and both vs 76% with no DA, p<0.001), followed closely by the EDA alone (82%, p=0.003). Finally, both DAs (M=19.5) and EDA alone (M=20.0) had better decisional conflict scores compared to usual care (M=25.8; p’s<0.001). We will present analyses that assess the impact of DAs on secondary outcomes and interactions with DA, patient, and clinical characteristics across each outcome. Conclusions: In one of the first randomized trials examining the comparative effectiveness of EDAs and PDAs on SDM in clinical medicine, both PDAs and EDAs improved shared decision-making, decisional conflict, and knowledge compared to patients receiving usual care.