Platelet RNA Biomarker of Ticagrelor-Responsive Genes Is Associated With Platelet Function and Cardiovascular Events.

BACKGROUND: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk. METHODS: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor. RNA sequencing was used to discover platelet genes affected by ticagrelor, and a subset of the most informative was summarized into a composite score and tested for validation. This score was further analyzed (1) in CD34+ megakaryocytes exposed to an P2Y12 inhibitor in vitro, (2) with baseline platelet function in healthy controls, (3) in peripheral artery disease patients (n=139) versus patient controls (n=30) without atherosclerosis, and (4) in patients with peripheral artery disease for correlation with atherosclerosis severity and risk of incident major adverse cardiovascular and limb events. RESULTS: Ticagrelor exposure differentially expressed 3409 platelet transcripts. Of these, 111 were prioritized to calculate a Ticagrelor Exposure Signature score, which ticagrelor reproducibly increased in discovery and validation cohorts. Ticagrelor's effects on platelets transcripts positively correlated with effects of P2Y12 inhibition in primary megakaryocytes. In healthy controls, higher baseline scores correlated with lower baseline platelet function and with minor bleeding while receiving ticagrelor. In patients, lower scores independently associated with both the presence and extent of atherosclerosis and incident ischemic events. CONCLUSIONS: Ticagrelor-responsive platelet transcripts are a biomarker for platelet function and cardiovascular risk and may have clinical utility for selecting patients with optimal risk:benefit for ticagrelor use.

Decline in use of high-risk agents for tight glucose control among older adults with diabetes in New York City: 2017-2022.

BACKGROUND: This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. METHODS: We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high-risk agent (insulin or insulin secretagogue). RESULTS: The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five-year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP-1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT-2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). CONCLUSIONS: We found an encouraging trend toward less use of high-risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population.

Social Determinants of Health and Diabetes-Related Distress in Patients With Insulin-Dependent Type 2 Diabetes: Cross-sectional, Mixed Methods Approach.

BACKGROUND: Social determinants of health (SDOH) refer to the social, economic, and psychosocial conditions that influence health. Lower levels of SDOH factors including income, education, and employment are associated with a higher prevalence of diabetes, poorer glycemic control, and increased diabetes-related mortality. Few studies have conducted a comprehensive evaluation of multiple SDOH factors in a population with type 2 diabetes mellitus (T2DM). OBJECTIVE: This study aimed to identify the range of SDOH challenges-including diabetes-related distress-that impact patients with insulin-dependent diabetes at an urban safety-net clinic using the 5-domain SDOH framework developed by the Healthy People 2020 initiative. METHODS: The pilot study used a cross-sectional, mixed methods approach. Participants were recruited from 3 programs within a general internal medicine clinic that provides ambulatory care for patients with uncontrolled T2DM. We administered an investigator-developed SDOH survey based on the Healthy People 2020 framework and the validated Diabetes Distress Scale (DDS), which assesses 4 domains of diabetes-related distress. One-on-one interviews were conducted to gain in-depth information about challenges. RESULTS: In total, 57 participants had an average hemoglobin A1c level of 11.0% (SD 2.6%). Overall, 92% (52/57) of participants had a barrier in at least one SDOH domain. SDOH challenges were most commonly reported in the domain of Health and Health Care (84%, 48/57), followed by Economic Stability (54%, n=31), Neighborhood and Built Environment (53%, n=30), Education and Health Literacy (47%, n=27), and Social and Community context (37%, n=21). The mean overall DDS score was 2.09 (SD 0.84), where scores of ≥2 indicate distress. Further, 79% (45/57) of participants had at least moderate diabetes-related distress in one of the 4 DDS domains. General themes that emerged from participant interviews included job interference with healthy behaviors, concerns about burdening others, challenges communicating with providers, and difficulty getting appointments in a timely manner. CONCLUSIONS: We found high levels of SDOH barriers across all 5 domains of the Center for Disease Control and Prevention's Healthy People 2020 framework, including significant levels of diabetes-related distress. Future programs to address SDOH barriers in patients with uncontrolled insulin-dependent diabetes should consider screening for and focusing on a wide range of challenges.

Study design of BETTER-BP: Behavioral economics trial to enhance regulation of blood pressure.

Background: Nonadherence to antihypertensive medications remains a persistent problem that leads to preventable morbidity and mortality. Behavioral economic strategies represent a novel way to improve antihypertensive medication adherence, but remain largely untested especially in vulnerable populations which stand to benefit the most. The Behavioral Economics Trial To Enhance Regulation of Blood Pressure (BETTER-BP) was designed in this context, to test whether a digitally-enabled incentive lottery improves antihypertensive adherence and reduces systolic blood pressure (SBP). Design: BETTER-BP is a pragmatic randomized trial conducted within 3 safety-net clinics in New York City: Bellevue Hospital Center, Gouveneur Hospital Center, and NYU Family Health Centers - Park Slope. The trial will randomize 435 patients with poorly controlled hypertension and poor adherence (<80% days adherent) in a 2:1 ratio (intervention:control) to receive either an incentive lottery versus passive monitoring. The incentive lottery is delivered via short messaging service (SMS) text messages that are delivered based on (1) antihypertensive adherence tracked via a wireless electronic monitoring device, paired with (2) a probability of lottery winning with variable incentives and a regret component for nonadherence. The study intervention lasts for 6 months, and ambulatory systolic blood pressure (SBP) will be measured at both 6 and 12 months to evaluate immediate and durable lottery effects. Conclusions: BETTER-BP will generate knowledge about whether an incentive lottery is effective in vulnerable populations to improve antihypertensive medication adherence. If successful, this could lead to the implementation of this novel strategy on a larger scale to improve outcomes.

Sociodemographic and clinical correlates of key outcomes from a Mobile Insulin Titration Intervention (MITI) for medically underserved patients.

BACKGROUND: Insulin titration is typically done face-to-face with a clinician; however, this can be a burden for patients due to logistical issues associated with in-person clinical care. The Mobile Insulin Titration Intervention (MITI) used basic cell phone technology including text messages and phone calls to help patients with diabetes find their optimal basal insulin dose (OID). OBJECTIVE: To evaluate sociodemographic and clinical correlates of reaching OID, text message response rate, and days needed to reach OID. METHODS: Primary care providers referred patients to MITI and nurses delivered the program. Three multivariable regression models quantified relationships between various correlates and primary outcomes. RESULTS: The sample included 113 patients from 2 ambulatory clinics, with a mean age of 50 years (SD = 10), 45% female, 79% Hispanic, 43% unemployed, and 46% uninsured. In regression models, baseline fasting blood glucose (FBG) was negatively associated with odds of reaching OID and 100% text responses, and positively associated with days to reach OID, p < .05). CONCLUSIONS: Patients with higher baseline FBG levels were less successful across outcomes and may need additional supports in future mHealth diabetes programs. PRACTICAL IMPLICATIONS: Basic cell phone technology can be used to adjust patients' insulin remotely, thereby reducing logistical barriers to care.