Effectiveness of a Population Health Intervention on Disparities in Hypertension Control: A Stepped Wedge Cluster Randomized Clinical Trial.

BACKGROUND: Disparities in hypertension control across race, ethnicity, and language have been a long-standing problem in the United States. OBJECTIVE: To assess whether a multi-pronged intervention can improve hypertension control for a target population and reduce disparities. DESIGN: This stepped wedge cluster randomized trial was conducted at 15 adult primary care clinics affiliated with Massachusetts General Hospital. PCPs were randomized to receive the intervention in twelve groups. PARTICIPANTS: The target population was patients who met one of the following criteria based on self-identification: (1) Asian, Black, Indigenous, multi-racial, or other race; (2) Hispanic ethnicity; or (3) preferred language other than English. Reference population was White, English-speaking patients. INTERVENTIONS: PCPs were given access to an online equity dashboard that displays disparities in chronic disease management and completed an equity huddle with population health coordinators (PHCs), which involved reviewing target patients whose hypertension was not well controlled. In addition, community health workers (CHWs) were available in some practices to offer additional support. MAIN MEASURES: The primary outcome was change in the proportion of target patients meeting the hypertension control goal when comparing intervention and control periods. KEY RESULTS: Of the 365 PCPs who were randomized, 311 PCPs and their 10,865 target patients were included in the analysis. The intervention led to an increase in hypertension control in the target population (RD 0.9%; 95% CI [0.3,1.5]) and there was a higher intervention effect in the target population compared to the reference population (DiD 2.1%; 95% CI [1.1, 3.1]). CONCLUSIONS: Utilizing data on disparities in quality outcome measures in routine clinical practice augmented by clinical support provided by PHCs and CHWs led to modest, but statistically significant, improvement in hypertension control among BIPOC, Hispanic, and LEP patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05278806.

Use of Cardioprotective Antidiabetic Medications in Adults With and Without Cardiovascular Disease, 2015 to March 2020.

BACKGROUND: Certain glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) can reduce cardiovascular risk in individuals with type 2 diabetes and cardiovascular disease (CVD). However, these medications can be expensive, potentially limiting their use. Objectives: The primary objective was to characterize the use of cardioprotective GLP-1 agonists and SGLT2-inhibitors among adults with diabetes with and without CVD. The secondary objective was to investigate the association of socioeconomic factors and health care utilization with the use of these medications. METHODS: Adults aged ≥20 years old with self-reported diabetes, A1c ≥6.5%, or fasting glucose ≥126 mg/dL were identified using the 2015 to March 2020 National Health and Nutrition Examination Survey. The primary outcome was the use of cardioprotective GLP-1 agonists or SGLT2-inhibitors compared in individuals with and without CVD. Secondary analyses included identification of socioeconomic factors and health care utilization associated with the use of cardioprotective antidiabetic medications, stratified by CVD status. Weighted analyses were conducted to account for the complex survey design. RESULTS: Use of cardioprotective antidiabetic medications was higher in adults with CVD compared to those without CVD (7.8% vs. 4.6%, P = 0.02), which was driven by the use of cardioprotective SGLT2-inhibitors (4.6% versus 1.9%, P = 0.002). Lower income level and less frequent health care visits within the past year were associated with lower likelihood of using these medications. CONCLUSION AND RELEVANCE: Despite preferential use in individuals with diabetes and CVD, the prevalence of cardioprotective antidiabetic medication use remains relatively low. Disparities in use appear to exist based on income level and health care utilization.

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice.

OBJECTIVE: The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched through September 7, 2022, using the keyword "tirzepatide." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with available results were included. DATA SYNTHESIS: Seven published phase 3, multicenter, randomized, parallel-group trials investigated efficacy and safety of tirzepatide versus placebo, semaglutide, insulin degludec, and insulin glargine for type 2 diabetes mellitus (T2DM) treatment. Studies included adults with uncontrolled T2DM and body mass index above 23 or 25 kg/m2. Hemoglobin A1c reduction from baseline was greater with tirzepatide across all studies with absolute reductions up to 3.02% and relative reductions ranging 0.44% (vs semaglutide) to 2.11% (vs placebo). Weight loss was significant. Incidence of gastrointestinal adverse effects (AE) was similar to semaglutide, and major cardiovascular events was similar to insulin glargine. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Studies demonstrated greater A1c lowering and weight reduction versus placebo and active comparators with AE similar to semaglutide, suggesting tirzepatide will be a valuable addition to the growing list of antidiabetic medications. Although tirzepatide's effects on major cardiovascular events was not increased when compared with insulin glargine, further evidence is needed to assess long-term implications on cardiovascular outcomes compared with agents with proven cardiovascular benefits. CONCLUSIONS: Tirzepatide has the potential to significantly impact the clinical management of T2DM, and results of ongoing clinical trials will help to fully determine its place in therapy.

Implementation of pharmacist recommendations in patients with type 2 diabetes enrolled in an employer-sponsored health plan.

BACKGROUND: The new, employee health plan (EHP) focused, population health initiative was established at Atrium Health Wake Forest Baptist in October 2020. The initiative's goals are to reduce health care costs and optimize patient care by providing patient-specific recommendations to help manage chronic disease states in the ambulatory care setting. This project's purpose is to quantify and categorize pharmacist recommendations implemented and not implemented. OBJECTIVE: Describe the implementation of pharmacist recommendations in a new, population health program. METHODS: Eligible patients: >18 years of age, diagnosed with type 2 diabetes, baseline HbA1c > 8%, and enrolled in the EHP. Patients were identified retrospectively through an electronic health record report. The primary endpoint assessed the proportion of pharmacist recommendations implemented. Interventions implemented and not implemented were categorized and reviewed for timely optimization of patient care and quality improvement. RESULTS: Overall, 55.7% of pharmacist recommendations were implemented. The most common reason recommendations were not implemented was that they were not addressed by the provider. The most common pharmacist recommendation was a drug therapy addition. Recommendations were implemented in a median time of 44 days. CONCLUSION: Over half of pharmacist recommendations were implemented. Provider communication and awareness was identified as a barrier for this new initiative. Increasing provider education and advertisement of pharmacist services should be considered to increase future implementation rates. The project identified a need for optimization of timely patient care by prioritizing patient charts prior to their next applicable provider visit.

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords "semaglutide" and "obesity," "weight," "high dose," "high-dose," or "2.4." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. DATA SYNTHESIS: Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. CONCLUSIONS: High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Racial and ethnic differences in blood pressure before and after the 2016 United States general election.

OBJECTIVES: The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro-level sociopolitical events with BP changes at the population-level. This study sought to characterize population-level changes in BP following the 2016 U.S. presidential election. METHODS: Using 2015-2018 National Health and Nutrition Examination Survey, we included participants aged ≥18 years during the same periods prior to (May to October 2015/2016) and after (May to October 2017/2018) the election. Survey-weighted data were analyzed to compare population-level systolic BP (SBP) and diastolic BP (DBP) pre- and post-election, stratified by race/ethnicity. Sex differences were also investigated. RESULTS: We observed significant increases in SBP among non-Hispanic (NH) Asian participants (+3.4 mmHg; p = .046), but not among other racial/ethnic participants. DBP increased among NH Black participants (+2.3 mmHg; p = .049) and Mexican American participants (+2.9 mmHg; p = .007), but not among other racial/ethnic participants. These changes appeared attributable to differential BP changes by sex. CONCLUSIONS: At the population-level, variable changes in BP were observed by race/ethnicity following the 2016 U.S. presidential election, possibly driven by SBP elevations among women.

Prescribing Patterns of Antihypertensive Agents and Blood Pressure Control Among Patients With Incident Stage 2 Hypertension.

Background: Initiation of appropriate antihypertensive therapy is crucial, particularly among patients with stage 2 hypertension, whom initiation of dual antihypertensive agents is suggested. Little is known regarding real-world prescribing of antihypertensive agents for patients with incident stage 2 hypertension. Objective: The primary objective was to describe prescribing patterns of antihypertensive therapy among patients with incident stage 2 hypertension. The secondary objectives included determining association of blood pressure (BP) control with initial multiple antihypertensive agents. Methods: Retrospective cohort analysis was conducted using electronic medical records from 6 primary care clinics between January 2014 and June 2019. Included patients were ≥18 years with an initial diagnosis of stage 2 hypertension, defined as BP ≥160/100 mm Hg Primary analysis was characterizing prescribing patterns of antihypertensive agents among patients with incident stage 2 hypertension. Investigation of BP control (<140/90 mm Hg) at 3 months of diagnosis was also performed. Results: We identified 261 patients with incident stage 2 hypertension (mean age, 52 years; 53.2% males; mean baseline BP, 162.1/100.1 mm Hg). Approximately 72% of patients were initiated on single antihypertensive agent, with the most common being angiotensin receptor blockers (ARBs; 25.7%) and angiotensin-converting-enzyme (ACE) inhibitors (24.6%). Commonly initiated multiple antihypertensive agents were ACE-inhibitor + thiazide-like diuretic (52.7%), followed by an ARB + thiazide-like diuretic (21.6%). Multiple antihypertensive therapy was associated with improved BP control at 3 months (adjusted odds ratio [OR], 3.54; 95% confidence interval [CI], 1.55-8.06). Conclusion: Majority of patients with incident stage 2 hypertension were prescribed initial single antihypertensive therapy, though better BP control at 3 months was seen among those initiated on multi-antihypertensive therapy.

Deactivation of Zeolites and Zeotypes in Methanol-to-Hydrocarbons Catalysis: Mechanisms and Circumvention.

Solid catalysts deployed in industrial processes often undergo deactivation, requiring frequent replacement or regeneration to recover the loss in activity. Regeneration occurs under conditions distinct from, and typically more harsh than, the catalysis, placing strict requirements on physicochemical material properties that divert catalyst optimization toward addressing regenerability over high activity and selectivity. Deactivation arises from mechanical, structural, or chemical modifications to active sites, promoters, and their surrounding matrices, and the prevailing mechanism for deactivation varies with the reaction, the catalyst, and the reaction conditions. Methanol-to-hydrocarbons processes utilize zeolites and zeotypes-crystalline, microporous oxides widely deployed as catalysts in the refining and petrochemical industries-as solid acid catalysts. Deposition and growth of highly unsaturated carbonaceous residues within the micropores congest molecular transport and block active sites, resulting in deactivation. In this Account, we describe studies probing the underlying mechanisms of deactivation in methanol-to-hydrocarbons catalysis and discuss examples of leveraging the acquired mechanistic insights to mitigate deactivation and prolong catalyst lifetime. These fundamental principles governing carbon deposition within zeolites and zeotypes provide opportunity to broaden versatility of processes for C1 valorization and to relax constraints imposed by hydrothermal catalyst stability considerations to achieve more active and more selective catalysis. Methanol-to-hydrocarbons catalysis occurs via a chain carrier mechanism. A zeolite/zeotype cavity hosts an unsaturated hydrocarbon guest to together constitute the supramolecular chain carrier that engages in a complex network of reactions for chain carrier propagation. Productive propagation reactions include olefin methylation, aromatic methylation, and aromatic dealkylation. Methanol undergoes unproductive dehydrogenation to formaldehyde via methanol disproportionation and olefin transfer hydrogenation. Subsequent alkylation reactions between formaldehyde and active olefinic/aromatic cocatalysts instigate cascades for dehydrocyclization, resulting in the formation of inactive polycyclic aromatic hydrocarbons and termination of the chain carrier. Addition of a distinct catalytic function that selectively decomposes formaldehyde mitigates chain carrier termination without disrupting the high selectivity to ethylene and propylene in methanol-to-hydrocarbons catalysis on small-pore zeolites and zeotypes. The efficacy of this bifunctional strategy to prolong catalyst lifetime increases with increasing proximity between the active sites for formaldehyde decomposition and the H+ sites of the zeolite/zeotype. Coprocessing sacrifical hydrogen donors mitigates chain carrier termination by intercepting, via saturation, intermediates along dehydrocyclization cascades. This strategy increases in efficacy with increasing concentration of the hydrogen donor and provides opportunity to realize steady-state methanol-to-hydrocarbons catalysis on small-pore zeolites and zeotypes.

Management and clinical outcomes in uterine malignant mixed Müllerian tumor: Lessons from a single-institution series.

Malignant mixed Müllerian tumor remains an important contributor to morbidity and mortality in women with uterine cancer. Surgery is the primary treatment modality, followed by chemotherapy and/or radiation for advanced disease or high-risk patients. Clinico-epidemiologic characteristics and outcomes in older versus younger women with Malignant mixed Müllerian tumor may differ. We analyzed and now report on 15 consecutive patients with uterine Malignant mixed Müllerian tumor treated at our institution from 2000 to 2018. The mean age at diagnosis was 65 years; 60% (9/15) patients were overweight/obese. Forty-six percent (7/15) had hypercholesterolemia, an association not previously linked with Malignant mixed Müllerian tumor in the literature. All patients but one had surgical excision of the tumor. A third of patients received adjuvant radiation therapy. A majority of patients received chemotherapy; the preferred regimen was carboplatin-paclitaxel. The patients older than 70 had a tendency towards a more advanced disease stage at diagnosis and a significantly shorter cancer-specific survival than their younger counterparts (6 months vs. 102 months (hazard ratio 1.32, p = 0.02)). Our study's conclusions are restricted due to its relatively small size, retrospective design, and some variation in the chemotherapy doses administered in individual patients. Larger studies are needed to confirm the significance of our findings.

Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy.

Pembrolizumab is a humanized antibody that targets programmed cell death receptor-1. This agent is approved for use in the treatment of several malignancies. While pruritus and papulo-erythematous rash are not uncommon with its use, severe reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis are very rare. We present herein a case of Stevens-Johnson syndrome occurring in a patient who had previously tolerated pembrolizumab without significant side effects for seven months. Prompt recognition of Stevens-Johnson syndrome/toxic epidermal necrolysis and discontinuation of the offending agent are paramount to ensure a favorable outcome.

Severe warm-antibody autoimmune hemolytic anemia due to multicentric Castleman disease: Responding to rituximab.

Castleman disease is a rare B-cell lymphoproliferative disorder characterized by lymph node enlargement with or without constitutional signs. Herein, we describe a unique patient with multicentric Castleman disease and retroviral infection who presented with a sudden onset of constitutional signs and was found to have severe warm-antibody autoimmune hemolytic anemia. Rituximab monotherapy yielded an excellent clinical response. We aim to inform the medical community of this rare paraneoplastic phenomenon in patients with Castleman disease and its effective management. Prompt recognition of this entity may help avoid costly diagnostic workups, excessive blood transfusions, and lengthy hospital stays.

Polymyalgia rheumatica due to pembrolizumab therapy.

Pembrolizumab is a humanized anti-programmed cell death 1 antibody used for the therapy of several malignancies. While autoimmune adverse events are not uncommon with this agent, they are typically mild and self-limiting. Severe autoimmunity is rare but can be life-threatening. Herein, we describe a unique case of severe proximal muscle weakness and joint pain shortly after beginning therapy with pembrolizumab. Work-up revealed elevated pro-inflammatory markers leading to the diagnosis of polymyalgia rheumatica. Steroids allowed for resolution of the joint pain. We call for awareness of this rare autoimmune toxicity with pembrolizumab.

Successful re-introduction of alectinib after inducing interstitial lung disease in a patient with lung cancer.

Alectinib is a member of the family of anaplastic lymphoma kinase inhibitors. This agent is effective in the treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung cancer and has excellent blood-brain barrier penetrability. It is generally well tolerated; however, significant toxicities such as interstitial lung disease have been reported. We present herein an instance of interstitial lung disease four weeks into alectinib treatment. Alectinib was held, and the patient showed clinical and radiographic improvement of her interstitial lung disease. Alectinib was then resumed at half dosage without further complications. Prompt recognition of adverse reactions to this targeted agent is paramount. Cessation of therapy may be needed on a case-to-case basis. However, as our case highlights, safe re-introduction of alectinib can be accomplished in some cases.

Cystic acne due to imatinib therapy for chronic myelocytic leukemia.

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of several malignancies. Its use, however, is associated with a number of toxic effects including adverse cutaneous reactions. Herein, we present a case of facial cystic acne in a patient receiving imatinib therapy for chronic myelocytic leukemia. This side effect resolved with cessation of therapy. To the best of our knowledge, this clinical entity has never been previously reported in the medical literature.

Impact of therapeutic modalities on disease-specific survival in older adults with glioblastoma: A single-institution retrospective cohort study.

The standard first-line therapy for glioblastoma consists of maximal surgical resection, followed by concurrent chemoradiotherapy. Optimal management for older glioblastoma patients is unknown as they have not been extensively studied in clinical trials. We report data from a series of 156 consecutive glioblastoma patients treated at our institution from 2007 to 2017. Compared to glioblastoma patients aged 70 or less, the patients older than 70 were less likely to undergo surgical resection (34% vs. 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs. 59%; p = 0.01) or radiation therapy (36% vs. 56%; p = 0.03). Disease-specific survival was significantly shorter in this age group (4.7 vs. 15.3 months; p = 0.002). Nonetheless, when older patients did undergo surgery or chemotherapy, the proportional improvement in cancer-specific survival was similar to the one recorded in younger patients, which is concordant with the findings of other published reports. A multidisciplinary input from neurosurgeons, medical and radiation oncologists, oncology pharmacists and geriatricians remain paramount for the optimal management of glioblastoma in patients older than 70.

Clinico-epidemiologic characteristics and patterns of care in Kaposi's sarcoma: Data from a single-institution series.

In the late 20th to early 21st century, most new Kaposi's sarcoma cases were associated with HIV coinfection and low CD4 T-cell counts. After introduction of effective antiretroviral therapy, the clinical and epidemiologic characteristics of Kaposi's sarcoma may have changed. We analyzed and now report on 27 consecutive Kaposi's sarcoma patients treated at our institution from 2007 to 2017. Most patients were HIV-positive Caucasian men on antiretroviral therapy; the average CD4 T-cell count was above the AIDS-defining level of 200 cells/mm3. Seven patients had Kaposi's sarcoma with mucosal involvement, and 20 had skin-only Kaposi's sarcoma. Mucosal Kaposi's sarcoma patients had a mean CD4 T-cell count of 83 cells/mm3 as opposed to 381 cells/mm3 for patients with skin-only involvement (p = 0.005). Survival was significantly compromised in both groups but even more so in Kaposi's sarcoma patients with mucosal involvement (306 vs. 609 days). Along with other reports, our findings suggest that Kaposi's sarcoma may develop in HIV patients in the modern era despite well-controlled HIV disease. This is significant since Kaposi's sarcoma remains an important contributor to morbidity and mortality in HIV-infected patients.

Evaluation of SAMe-TT2R2 Score on Predicting Success With Extended-Interval Warfarin Monitoring.

BACKGROUND: In patients with stable international normalized ratios, 12-week extended-interval warfarin monitoring can be considered; however, predictors of success with this strategy are unknown. The previously validated SAMe-TT2R2 score (considering sex, age, medical history, treatment, tobacco, and race) predicts anticoagulation control during standard follow-up (every 4 weeks), with lower scores associated with greater time in therapeutic range. OBJECTIVE: To evaluate the ability of the SAMe-TT2R2 score in predicting success with extended-interval warfarin follow-up in patients with previously stable warfarin doses. METHODS: In this post hoc analysis of a single-arm feasibility study, baseline SAMe-TT2R2 scores were calculated for patients with ≥1 extended-interval follow-up visit. The primary analysis assessed achieved weeks of extended-interval follow-up according to baseline SAMe-TT2R2 scores. RESULTS: A total of 47 patients receiving chronic anticoagulation completed a median of 36 weeks of extended-interval follow-up. The median baseline SAMe-TT2R2 score was 1 (range 0-5). Lower SAMe-TT2R2 scores appeared to be associated with greater duration of extended-interval follow-up achieved, though the differences between scores were not statistically significant. No individual variable of the SAMe-TT2R2 score was associated with achieved weeks of extended-interval follow-up. Analysis of additional patient factors found that longer duration (≥24 weeks) of prior stable treatment was significantly associated with greater weeks of extended-interval follow-up completed ( P = 0.04). Conclusion and Relevance: This pilot study provides limited evidence that the SAMe-TT2R2 score predicts success with extended-interval warfarin follow-up but requires confirmation in a larger study. Further research is also necessary to establish additional predictors of successful extended-interval warfarin follow-up.

Defining Team Effort Involved in Patient Care from the Primary Care Physician's Perspective.

BACKGROUND: A better understanding of the attributes of patients who require more effort to manage may improve risk adjustment approaches and lead to more efficient resource allocation, improved patient care and health outcomes, and reduced burnout in primary care clinicians. OBJECTIVE: To identify and characterize high-effort patients from the physician's perspective. DESIGN: Cohort study. PARTICIPANTS: Ninety-nine primary care physicians in an academic primary care network. MAIN MEASURES: From a list of 100 randomly selected patients in their panels, PCPs identified patients who required a high level of team-based effort and patients they considered complex. For high-effort patients, PCPs indicated which factors influenced their decision: medical/care coordination, behavioral health, and/or socioeconomic factors. We examined differences in patient characteristics based on PCP-defined effort and complexity. KEY RESULTS: Among 9594 eligible patients, PCPs classified 2277 (23.7 %) as high-effort and 2676 (27.9 %) as complex. Behavioral health issues were the major driver of effort in younger patients, while medical/care coordination issues predominated in older patients. Compared to low-effort patients, high-effort patients were significantly (P < 0.01 for all) more likely to have higher rates of medical (e.g. 23.2 % vs. 6.3 % for diabetes) and behavioral health problems (e.g. 9.8 % vs. 2.9 % for substance use disorder), more frequent primary care visits (10.9 vs. 6.0 visits), and higher acute care utilization rates (25.8 % vs. 7.7 % for emergency department [ED] visits and 15.0 % vs. 3.9 % for hospitalization). Almost one in five (18 %) patients who were considered high-effort were not deemed complex by the same PCPs. CONCLUSIONS: Patients defined as high-effort by their primary care physicians, not all of whom were medically complex, appear to have a high burden of psychosocial issues that may not be accounted for in current chronic disease-focused risk adjustment approaches.