Mona Alshahawey

Background: Despite strong evidence supporting cardiovascular and kidney benefits of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) in patients with type 2 diabetes, prescribing rates remain suboptimal. The aim of this study was to assess clinicians' knowledge and comfort prescribing SGLT2i and GLP‐1 RA in clinical practice and factors influencing prescribing of these agents. Methods: This multi‐methods study used questionnaires to assess self‐reported knowledge and comfort prescribing SGLT2i and GLP‐1 RA, and semi‐structured interviews based on the Consolidated Framework for Implementation Research (CFIR) to assess factors affecting prescribing decisions among 21 clinicians (12 primary care physicians, 4 pharmacists, 5 nurse practitioners) at a large community‐based health system in Virginia. Questionnaire results were analyzed using descriptive statistics, and interviews used a two‐phase analytic approach combining inductive and deductive coding. Results: Clinicians self‐reported high knowledge (7.9/10) and comfort (8.1 and 8.4/10) prescribing SGLT2i and GLP‐1 RA but identified multiple implementation barriers. The most significant barriers were insurance coverage and out‐of‐pocket costs, with prior authorization requirements delaying therapy initiation. Medicare beneficiaries faced particularly challenging access due to coverage gaps and ineligibility for manufacturer assistance programs. Organizational factors, including high workload, limited appointment time, and the absence of automated patient identification systems, hindered consistent prescribing. Medication burden, side effects, and aversion to injectable medications emerged as patient‐related barriers. Facilitators included strong clinical evidence supporting these agents, organizational culture supportive of innovation, and access to pharmacist support. Conclusion: Despite high self‐reported knowledge and comfort prescribing SGLT2i and GLP‐1 RA, clinicians identified barriers to their use in clinical practice at the patient, clinician, organizational, and medication access levels. Future work should identify the best implementation strategies to address these barriers.

Hypertension is a known modifiable risk factor for Alzheimer’s disease and related dementia (ADRD). However, it is unknown how variance in hypertension control, antihypertensive medications, and social determinants of health, such as social deprivation index (SDI), influence the risk of developing ADRD. Validated hypertension computable phenotype algorithms were applied to electronic health record data from the OneFlorida Data Trust (1/1/2013–12/31/2016), to identify apparent treatment‐resistant hypertension (aTRH), and hypertension‐control levels (well‐controlled hypertension, intermediate‐controlled hypertension, uncontrolled hypertension). The primary outcome was a new ADRD diagnosis using validated ICD‐9/10 codes. Multiple adjusted stepwise logistic regression models were used to identify factors associated with ADRD development. ADRD cumulative hazard incidence per hypertension control levels was assessed using the Nelson–Aalen estimator and log‐rank test. A total of 57,273 hypertension patients with 6401 (11%) incident ADRD cases were included in the analysis. The average age was 67 years, with 57% females and 32% identifying as Black or African American. aTRH was a significant ADRD predictor (OR: 1.327, 95% CI: 1.234–1.427), compared to other hypertension phenotypes. aTRH was also significantly associated with a higher incidence of ADRD over time ( P < 0.0001). Patients prescribed thiazide diuretics (OR: 0.894, 95% CI: 0.837–0.956) and fixed‐dose combination medications (OR: 0.804, 95% CI: 0.732–0.882) had a lower risk of ADRD. A linear relationship between SDI quartiles and ADRD risk was found. aTRH was significantly associated with the development of ADRD. Our study also highlights the importance of comprehensive hypertension control and socioeconomic interventions in preventing or reducing ADRD risk in hypertension patients.

Purpose: Patients on regular hemodialysis (HD) are at the highest risk of developing anemia. Vitamin D deficiency is more prevalent in HD patients. Recent studies have suggested that improving vitamin D status can reduce both anemia and the need for higher recombinant human erythropoietin (EPO) dosing. This study is to demonstrate the pleiotropic effects of two regimens of cholecalciferol intake on the hemoglobin (Hgb) levels, ferritin levels, transferrin saturation (TSAT), total iron-binding capacity (TIBC) and the erythropoietin sensitivity index (ERI) in HD patients. Methods: A prospective, randomized, single blinded trial was conducted to evaluate the effect of weekly versus monthly cholecalciferol administration on anemia parameters and erythropoietin sensitivity in hemodialysis (HD) patients. Fifty eligible patients undergoing HD were randomly allocated to receive either weekly doses of 50,000 IU or monthly doses of 200,000 IU cholecalciferol. Various parameters including Hgb levels, ferritin levels, TSAT, TIBC, ERI, and cumulative dose of erythropoietin (EPO) were evaluated both at baseline and at endpoint. This study was registered at Clinicaltrial.gov, identifier number (NCT05922696), registered 2023/06/20 (Retrospectively registered). Results: Adding weekly or monthly cholecalciferol to standard HD care for three months resulted in a 72% reduction in EPO doses for thirty-six out of fifty patients. Both regimens significantly increased Hgb levels, with the weekly regimen showing a greater increase (+ 2.67 g/dl vs. + 0.70 g/dl; P < 0.001). The weekly regimen also led to a significant increase in TSAT (P = 0.005) and a decrease in ferritin levels (P = 0.03). Moreover, the weekly regimen significantly reduced EPO doses (−11,600 IU vs. −6,160 IU) and ERI (−4.76 vs. −2.68; P < 0.001) compared to the monthly regimen. Conclusion: Cholecalciferol demonstrated a beneficial impact on anemia in HD patients. Weekly 50,000 IU regimen had better control over Hgb, TSAT, TIBC, EPO dosing, and erythropoietin sensitivity compared to the monthly 200,000IU regimen. ClinicalTrials.gov registration number: NCT05922696.

Background: Denosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied. Results: The cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome. Conclusion: The model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data.

Background: Emerging evidence links vitamin D deficiency to oxidative stress (OS) and inflammation, posing ongoing risks to cardiovascular outcomes in hemodialysis (HD) patients. Despite this, current data are lacking regarding the optimal approach or schedule for administering vitamin D in this population. This study investigated the effectiveness of oral weekly versus oral monthly cholecalciferol supplementation on 25-hydroxy vitamin D (25(OH)D) levels, oxidative stress, inflammatory indicators, and secondary hyperparathyroidism in HD population. HD patients (N = 50) were randomly allocated to Group A (oral weekly 50,000 IU cholecalciferol) or Group B (oral monthly 200,000 IU cholecalciferol) for a 3 months duration. Serum levels of 25(OH)D, malondialdehyde (MDA), superoxide dismutase (SOD), high sensitivity C-reactive protein (HsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and intact parathyroid hormone (iPTH) were assessed at baseline and upon completion of the study. Results: A notable increase in serum 25(OH)D levels observed in both groups, with Group A showing a notably greater increase (p = 0.003). Group A demonstrated significant reductions in serum MDA and increases in SOD, along with declines in hsCRP and NLR levels, which were not observed in Group B. Moreover, Group A exhibited a greater drop in iPTH (ΔiPTH = − 30 pg/mL vs. − 3 pg/mL) compared to Group B. Clinicaltrial.gov: NCT05460338, registered 13/07/2022. Conclusions: Weekly oral 50,000 IU cholecalciferol supplementation emerges as a tolerable, safe and effective approach for restoring vitamin D levels in HD patients, while concurrently mitigating inflammation, OS, and secondary hyperparathyroidism. This finding suggests that the more frequent the administration of oral cholecalciferol, the higher the efficiency observed.

Hypertension (HTN) remains a significant public health concern and the primary modifiable risk factor for cardiovascular disease, which is the leading cause of death in the United States. We applied our validated HTN computable phenotypes within the All of Us Research Program to uncover prevalence and characteristics of HTN and apparent treatment-resistant hypertension (aTRH) in United States. Within the All of Us Researcher Workbench, we built a retrospective cohort (January 1, 2008–July 1, 2023), identifying all adults with available age data, at least one blood pressure (BP) measurement, prescribed at least one antihypertensive medication, and with at least one SNOMED “Essential hypertension” diagnosis code. We identified 99 461 participants with HTN who met the eligibility criteria. Following the application of our computable phenotypes, an overall population of 81 462 were further categorized to aTRH (14.4%), stable-controlled HTN (SCH) (39.5%), and Other HTN (46.1%). Compared to participants with SCH, participants with aTRH were older, more likely to be of Black or African American race, had higher levels of social deprivation, and a heightened prevalence of comorbidities such as hyperlipidemia and diabetes. Heart failure, chronic kidney disease, and diabetes were the comorbidities most strongly associated with aTRH. β-blockers were the most prescribed antihypertensive medication. At index date, the overall BP control rate was 62%. All of Us provides a unique opportunity to characterize HTN in the United States. Consistent findings from this study with our prior research highlight the interoperability of our computable phenotypes.

Purpose: Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. Methods: This national, cross sectional study utilized a questionnaire to collect oncologists’ perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists’ approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. Results: Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists’ approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. Conclusion: Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.