Real-world clinical outcomes with avelumab in patients with Merkel cell carcinoma treated in the USA: a multicenter chart review study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neuroendocrine neoplasm with annual incidence rates of 0.13-1.6 cases/100,000/year worldwide as of 2018. Chemotherapy for metastatic MCC (mMCC) has high objective response rates (ORRs), but responses are not durable and overall survival (OS) is poor. Avelumab (anti-programmed death-ligand 1) has demonstrated meaningful survival benefit and durable responses in clinical trials for mMCC. This study investigated real-world clinical outcomes in avelumab-treated patients with advanced (stage IIIB/IV) MCC in US academic medical centers. METHODS: We conducted a retrospective chart review of patients with advanced MCC who initiated avelumab between March 1, 2017, and July 31, 2019, at six US academic centers. Data were requested for eligible patients from index date through December 31, 2020. Descriptive analyses were conducted to assess demographic and clinical characteristics, real-world ORR (rwORR), real-world duration of response, real-world progression-free survival (rwPFS), and OS. RESULTS: Ninety patients with advanced MCC (82%, stage IV; 18%, stage IIIB) received avelumab. Median follow-up was 20.8 months (95% CI: 19.1 to 24.2). Median age was 68 years (range, 48-83), and the majority of patients were men (58%) and white (93%). The primary tumor was most commonly located on the lower limb (38%), with metastases mostly located in lymph nodes (68%), lung (52%), and viscera (52%). Approximately 42% and 26% of patients had an Eastern Cooperative Oncology Group performance status of 2 and 3, respectively. Seventy-three patients (81%) received avelumab as first-line treatment of advanced MCC, while 17 (19%) received avelumab as second-line or later treatment. The median duration of avelumab treatment was 13.5 months (95% CI: 6.4 to 30.6), with 42% of patients still receiving avelumab by the end of follow-up. Patients with avelumab treatment had an rwORR of 73% (95% CI: 64 to 83), median rwPFS of 24.4 months (95% CI: 8.31 to not estimable (NE)), and median OS of 30.7 months (95% CI: 11.2 to NE). CONCLUSIONS: This real-world study of patients with advanced MCC demonstrated that avelumab treatment resulted in a high response rate with durable responses and prolonged survival. The study findings validate the results demonstrated in prospective clinical trials and other observational studies.

A Real-World Comparative Effectiveness Analysis of Thromboprophylactic Use of Enoxaparin Versus Unfractionated Heparin in Abdominal Surgery Patients in a Large U.S. Hospital Database.

Introduction: Little is known about outcomes associated with enoxaparin versus unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in abdominal surgery patients in U.S. clinical practice. The purpose of this study was to compare VTE, all-cause mortality, PE-related in-hospital mortality, and hospital costs during abdominal surgery hospitalization and the 90 days post-discharge between patients who received enoxaparin versus UFH prophylaxis. Materials and Methods: Using the Premier Healthcare Database, abdominal surgery patients who received at least 1 day of VTE prophylaxis with enoxaparin or UFH were identified between January 1, 2010 and September 30, 2016. Clinical outcomes were assessed using multivariable logistic regression models and cost outcomes were assessed using generalized linear models. Results: Of 363,669 patients identified, 59% received enoxaparin and 41% UFH. In adjusted analyses, there were statistically significant lower odds of VTE (OR 0.80; 95% CI 0.65-0.97), all-cause mortality (OR 0.67; 95% CI 0.60-0.75), and major bleeding (OR 0.88; 95% CI 0.82-0.94) during the hospitalization for enoxaparin versus UFH, but no differences during the 90-days post-discharge or for PE-related mortality. There was a statistically significant lower total hospital cost with enoxaparin versus UFH during index hospitalization ($8,913 vs $9,017, P < .0001), but not post-discharge ($3,342 vs $3,368, P = .42). Unadjusted rates of heparin-induced thrombocytopenia (index:0.1% vs 0.3%; post-discharge: 0.02% vs 0.06%) were reported for enoxaparin and UFH, respectively. Conclusion: In contemporary U.S. hospital practice, statistically significant lower odds of VTE, all-cause mortality and major bleeding with enoxaparin versus UFH prophylaxis were found during abdominal surgery hospitalizations.

Are caregivers ready for digital? Caregiver preferences for health technology tools to monitor medication adherence among patients with serious mental illness.

Background: Adherence to antipsychotic medication is critical for bipolar disorder (BPD), major depression (MDD) and schizophrenia (SCZ) patients. Digital tools have emerged to monitor medication adherence along with tracking general health. Evidence on physician or patient preferences for such tools exists but is limited among caregivers. The study objective was to assess preferences and willingness-to-pay (WTP) for medication adherence monitoring tools among caregivers of SMI patients. Methods: A web-based survey was administered to caregivers of adult SMI patients. Twelve discrete choice questions comparing adherence monitoring tools that varied across two attribute bundles: (1) tool attributes including source of medication adherence information, frequency of information updates, access to adherence information, and physical activity, mood, and rest tracking, and (2) caregiver monthly out-of-pocket cost attribute were administered to caregiver respondents. Attributes were parameterized for both digital and non-digital tools. Random utility models were used to estimate caregivers' preferences and WTP. Results: Among 184 study-eligible caregivers, 57, 61 and 66 participants cared for BPD, MDD, and SCZ patients, respectively. Caregivers highly preferred (odds ratio (OR): 7.34, 95% confidence interval (CI): 5.00-10.79) a tool that tracked medication ingestion using a pill embedded with an ingestible event market (IEM) sensor and tracked patients' physical activity, mood, and rest than a non-digital pill organizer. Additionally, caregivers were willing to pay $255 per month (95% CI: $123-$387) more for this tool compared to a pill organizer. Conclusion: Caregivers of SMI patients highly preferred and were willing to pay more for digital tools that not only measures medication ingestion but also tracks general health.

Real-World Comparative Effectiveness and Cost Comparison of Thromboprophylactic Use of Enoxaparin versus Unfractionated Heparin in 376,858 Medically Ill Hospitalized US Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication in medically ill inpatients. Enoxaparin or unfractionated heparin (UFH) thromboprophylaxis has been shown to reduce VTE in clinical trials; however, comparative effectiveness and differences in hospital costs are unknown in US hospital practice. OBJECTIVE: This study compared clinical and economic outcomes between enoxaparin and UFH thromboprophylaxis in medically ill inpatients. METHODS: A retrospective cohort study was conducted using the Premier Healthcare Database between 1 January 2010 and 30 September 2016. Inpatients aged ≥ 18 years with a ≥ 6-day hospital stay for serious medical conditions were included. Two patient groups receiving thromboprophylaxis were identified during hospitalization: one receiving enoxaparin and other receiving UFH. Regression models were constructed to compare VTE events, in-hospital mortality, pulmonary embolism (PE)-related mortality, major bleeding, and total hospital costs during both the index hospitalization and the 90-day readmission period between the two groups. RESULTS: A total of 242,474 and 134,384 inpatients received enoxaparin or UFH for thromboprophylaxis, respectively. Compared with UFH prophylaxis, enoxaparin was significantly associated with 15%, 9%, 33%, and 41% reduced odds of VTE, in-hospital mortality, PE-related mortality, and major bleeding, respectively, during index hospitalization, and 10% and 19% reduced odds of VTE and bleeding, respectively, during the readmission period. Mean total hospital costs were significantly lower in patients receiving enoxaparin prophylaxis than in those given UFH. CONCLUSIONS: Thromboprophylaxis with enoxaparin was associated with significantly reduced in-hospital VTE events, death, and major bleeding and lower hospital costs compared with UFH in hospitalized medically ill patients.

The role of epidemiology in informing United States childhood immunization policy and practice.

One of the ten greatest public health achievements is childhood vaccination because of its impact on controlling and eliminating vaccine-preventable diseases (VPDs). Evidence-based immunization policies and practices are responsible for this success and are supported by epidemiology that has generated scientific evidence for informing policy and practice. The purpose of this report is to highlight the role of epidemiology in the development of immunization policy and successful intervention in public health practice that has resulted in a measurable public health impact: the control and elimination of VPDs in the United States. Examples in which epidemiology informed immunization policy were collected from a literature review and consultation with experts who have been working in this field for the past 30 years. Epidemiologic examples (e.g., thimerosal-containing vaccines and the alleged association between the measles, mumps, and rubella (MMR) vaccine and autism) are presented to describe challenges that epidemiologists have addressed. Finally, we describe ongoing challenges to the nation's ability to sustain high vaccination coverage, particularly with concerns about vaccine safety and effectiveness, increasing use of religious and philosophical belief exemptions to vaccination, and vaccine hesitancy. Learning from past and current experiences may help epidemiologists anticipate and address current and future challenges to respond to emerging infectious diseases, such as COVID-19, with new vaccines and enhance the public health impact of immunization programs for years to come.

Role of mitochondrial fission and fusion in cardiomyocyte contractility.

BACKGROUND: Mitochondria constitute 30% of cell volume and are engaged in two dynamic processes called fission and fusion, regulated by Drp-1 (dynamin related protein) and mitofusin 2 (Mfn2). Previously, we showed that Drp-1 inhibition attenuates cardiovascular dysfunction following pressure overload in aortic banding model and myocardial infarction. As dynamic organelles, mitochondria are capable of changing their morphology in response to stress. However, whether such changes can alter their function and in turn cellular function is unknown. Further, a direct role of fission and fusion in cardiomyocyte contractility has not yet been studied. In this study, we hypothesize that disrupted fission and fusion balance by increased Drp-1 and decreased Mfn2 expression in cardiomyocytes affects their contractility through alterations in the calcium and potassium concentrations. METHODS: To verify this, we used freshly isolated ventricular myocytes from wild type mouse and transfected them with either siRNA to Drp-1 or Mfn2. Myocyte contractility studies were performed by IonOptix using a myopacer. Intracellular calcium and potassium measurements were done using flow cytometry. Immunocytochemistry (ICC) was done to evaluate live cell mitochondria and its membrane potential. Protein expression was done by western blot and immunocytochemistry. RESULTS: We found that silencing mitochondrial fission increased the myocyte contractility, while fusion inhibition decreased contractility with simultaneous changes in calcium and potassium. Also, we observed that increase in fission prompted decrease in Serca-2a and increase in cytochrome c leakage leading to mitophagy. CONCLUSION: Our results suggested that regulating mitochondrial fission and fusion have direct effects on overall cardiomyocyte contractility and thus function.