Reduction of Factor VIII Inhibitor Titers During Immune Tolerance Induction With Recombinant Factor VIII‐Fc Fusion Protein

The development of inhibitors toward factor VIII (FVIII) is a common and serious complication of hemophilia A (HA) therapy. Patients with hemophilia who develop inhibitors often undergo time‐ and resource‐intensive immune tolerance induction (ITI) protocols. We report a 15‐month‐old male with severe HA and a high‐titer inhibitor that occurred while receiving prophylactic treatment with recombinant FVIII (rFVIII), in whom significant inhibitor titer reduction was achieved with thrice weekly infusions of a new, prolonged half‐life rFVIII‐Fc fusion protein product (trade name Eloctate). Further studies are warranted to explore the potential of Eloctate in ITI protocols.     

Geriatrics: Moving forward with 2020 vision

Geriatricians have long debated the parameters, positioning, and prospects of their specialty. The year 2020 started full of promise as many organizations anticipated assessing themselves using perfect, or 2020, vision. While challenging on several levels, the momentous combination of events in 2020—the COVID-19 pandemic, Racial Justice Movement, and the November elections—provided Geriatric Medicine several opportunities to firmly secure a position in the mainstream. As we reflect on the new perspectives, programs, and partnerships initiated in 2020, five broader lessons emerge that can help safeguard the future of Geriatrics: the field could employ more intentional “direct to consumer” marketing strategies, expand the scope of what it means to be a patient advocate, pursue new strategic partnerships, take the opportunity to address racial injustice, and leverage existing skillsets to expand scope of care for patients. Given the interdisciplinary nature of Geriatrics, it is fitting that many of these lessons build upon this collaborative philosophy and are derived from domains outside of health care. So in an unexpected way, the events of 2020 may actually help Geriatrics see, with 2020 vision, how to remain mainstream. With this new clarity, Geriatrics holds renewed promise to truly become specialists in whole-person care and it is our hope that, with insight from the lessons shared here, the specialty brings this vision to fruition in the current decade and beyond.     

Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients

Background

Axillary lymph node dissection (ALND) is recommended for patients with clinically node-positive breast cancer and carries a risk of lymphedema >30 %. Patients with node-positive breast cancer may consider neoadjuvant chemotherapy, which can reduce node positivity. We sought to determine if neoadjuvant chemotherapy reduced the risk of lymphedema in patients undergoing ALND for node-positive breast cancer.

Methods

The 229 patients who underwent unilateral ALND and chemotherapy were divided into two groups: 30 % (68/229) had neoadjuvant and 70 % (161/229) had adjuvant chemotherapy. Prospective arm volumes were measured via perometry preoperatively and at 3- to 7-month intervals after surgery. Lymphedema was defined as relative volume change (RVC) ≥10 %, >3 months from surgery. Kaplan–Meier curves and multivariate regression models were used to identify risk factors for lymphedema.

Results

Fifteen percent (10/68) of neoadjuvant patients compared with 23 % (37/161) of adjuvant patients developed RVC ≥10 % (hazard ratio = 0.76, p = 0.39). For all patients, body mass index was significantly associated with lymphedema (p = 0.0003). For neoadjuvant patients, residual lymph node disease after chemotherapy was associated with a ninefold greater risk of lymphedema compared to those without residual disease (p = 0.038).

Conclusions

Patients who underwent neoadjuvant chemotherapy did not have a statistically significant reduction in risk of lymphedema. Among patients who receive neoadjuvant chemotherapy, residual lymph node disease predicted a greater risk of lymphedema. These patients should be closely monitored for lymphedema and possible early intervention for the condition.     

Clinical Sobriety Assessment by Emergency Physicians in Blunt Trauma Patients with Acute Alcohol Exposure

Background: Alcohol use increases injury risk and severity. However, few studies have evaluated the ability of emergency physicians (EPs) to accurately determine sobriety. Objectives: To determine the predictive value of clinical sobriety assessment by EPs in blunt trauma patients with acute alcohol use. Materials and Methods: Blunt trauma patients, aged 18–65 years with suspected acute alcohol use, were prospectively enrolled in the study. EPs assessed study subjects before sample collection for blood alcohol level (BAL) and urine drug screen measurement. Alcohol exposure was considered significant if BAL was ≥ 80 mg/dL. Sobriety (non-significant alcohol exposure) was defined as a BAL < 80 mg/dL. EP sobriety assessment was compared to measured BAL and predictive values were calculated. Agreement on significance of alcohol exposure occurred if EP-estimated BAL > 80 mg/dL agreed with measured BAL > 80 mg/dL, or estimated BAL < 80 mg/dL agreed with measured BAL < 80 mg/dL. Chi-squared analysis was used to compare the proportion of correct physician assessments among patients with sobriety and those with significant alcohol exposure. Results: Of 158 enrolled subjects, 153 completed clinical assessment. EP assessment had a predictive value of 83% (95% confidence interval [CI] 77–90%) for significant alcohol exposure and 69% (95% CI 60–78%) for sobriety. Agreement on the significance of alcohol exposure was 82% (125/153; 95% CI 76–88%). EPs identified 32% (11/34; 95% CI 17–48%) of sober patients, but identified 96% (114/119; 95% CI 92–99%) of patients with significant alcohol exposure. EP assessment was significantly less accurate in identifying sober patients (p < 0.01). Conclusions: Emergency physicians identified significant recent alcohol exposure in blunt trauma patients 96% of the time. However, clinical assessment by EPs in blunt trauma patients with recent alcohol use had only moderate predictive value for significant alcohol exposure. Sober patients were frequently misidentified as having significant alcohol exposure.     

What Is Next for Pharmacoeconomics and Outcomes Research in Asia?

OBJECTIVES: Pharmacoeconomics and outcomes research have the potential for rapid adoption in the Asia Pacific region. Nevertheless, the region is characterized by great diversity in social and economic development, ethnicity, population size, health-care system, culture, language, and religion. Thus, the rate of adoption is also quite diverse across the region. METHODS: Among the countries reviewed in this article, governments take varying levels of interest in applying this research in health policy decisions. For example, some countries have already implemented systems that require pharmacoeconomic studies as one component of a new pharmaceutical product's approval for reimbursement, whereas others recommend such data but do not require it in policy and medical decision making. The literature in the countries reviewed is actually quite robust given the early stages of development of this field in most countries. The academic community has members trained in this field of research in all the countries reviewed and some universities have established departments whereas others have just introduced a few classes in the area. RESULTS: At the moment, pharmacoeconomics and outcomes research are being conducted mainly by academics. In addition, some pharmaceutical researchers are active and pharmaceutical companies are currently preparing to conduct more of this research as part of their strategy for Asian drug development. CONCLUSIONS: Prospects for future growth and development in this field are quite good in Asia as rapid healthcare inflation, increasing rates of chronic conditions and aging population, and increasing technology diffusion will underpin the need for greater awareness of the need to incorporate economic efficiency into the health-care systems.