Bronchiolitis is the leading cause of infant hospitalizations in the United States. Despite clinical practice guidelines discouraging the utilization of non–evidence-based therapies, there continues to be wide variation in care and resource utilization. A pre-post physician focused educational intervention was conducted with the aims to reduce the use of non–evidence-based medical therapies, including bronchodilators, among patients admitted for bronchiolitis. Among patients meeting inclusion criteria (pre: n = 45; post: n = 47), bronchodilator use decreased by 50% (P < .001). Antibiotic use increased by 9% (P < .02), although results remained within published acceptable utilization rates of less than 19%. There were no statistical differences in chest X-ray, respiratory viral panel, and steroid use. There were no differences in number of pediatric intensive care unit transfers, 30-day readmission rates, and mean length of stay. The findings demonstrate that a physician-focused educational intervention highlighting American Academy of Pediatrics clinical practice guidelines resulted in reduced utilization of bronchodilators.
2503 Poster Board II-480 Because venous thromboembolism (VTE) often occurs as a complication of cancer and chemotherapy, cancer patients have a 47-fold elevation of risk of VTE compared to the general population (Khorana et al., Journal of Thrombosis and Haemostasis 2007). However, until recently there was not a model to accurately predict which cancer patients would experience a VTE during their treatment. Khorana et al. have developed such a model (Khorana et al., Blood 2008). We conducted a retrospective study to test the effectiveness of Khorana and colleagues' clinical model at predicting risk of VTE in patients with metastatic cancer. We collected data from an outpatient oncology clinic for 112 patients with solid tumors or malignant lymphoma who had undergone active chemotherapy in the last two years. The data included the five predictive variables outlined in Khorana et al.'s model: site of cancer (2 points for a very high-risk site, 1 point for a high-risk site); a platelet count of 350 × 109/L or more; hemoglobin less than 100g/L and or/use of erythropoiesis-stimulating agents; leukocyte count more than 11 × 109/L; and body mass index of 35kg/m2 or more (1 point each) (Khorana et al., Blood 2008). All data was collected on the first day of chemotherapy or the most recent labs before the start of chemotherapy. A score of 0 points represented a low risk of VTE, 1-2 points represented an intermediate risk and 3-4 points represented a high risk. There were 20 low risk patients, 63 intermediate risk and 29 high risk. We found that the clinical model accurately predicted which patients would experience a VTE (Table 1). Of the total 112 patients, 23 experienced a VTE. We determined that patients considered high risk were 8-fold more likely to experience a VTE as compared to low risk patients (see Table 1). Kuderer et al. demonstrated that this risk model also predicts overall mortality for patients receiving chemotherapy (Kuderer et al., ASH 2009). The results of our study also showed a strong correlation between overall mortality and a higher risk score. The mortality rate of high risk patients during the trial period was 69.0% compared to 30.0% of low risk patients and 42.9% of intermediate risk patients. Our retrospective review validates Khorana and colleagues' clinical model to predict VTE and survival rates in cancer patients. Our results, combined with data from previous studies, indicate that patients who are at risk for VTE also have a higher mortality rate. With an accurate predictive model, primary prophylaxis treatment for VTE could be considered for high risk patients. Disclosures: No relevant conflicts of interest to declare.
Aminocaproic acid (Amicar), an inhibitor of fibrinolysis, is indicated for the management of bleeding in thrombocytopenia, hepatic cirrhosis, cardiac surgery and neoplastic disease, such as cancer of the prostate, lung, stomach and cervix (package insert). Vitamin K, administered concurrently with aminocaproic acid, aids in coagulation through stimulation of clotting factors II, VII, IX and X (Pereira and Phan 2004). Though aminocaproic acid has been available since 1964, there is limited use of the drug within the medical field, most likely due to concerns about thrombosis. These concerns are confirmed through previous studies (Saba et al. 1994, Wells 2002) and the label cautions physicians against prescribing the drug in patients with upper urinary tract bleeding due to risk of thrombosis (package insert). We have treated hundreds of patients with these drugs over the past ten years (80 administrations across 71 hospitalized patients in the past 19 months), primarily in our population of Jehovah’s Witnesses who refuse blood product support due to religious beliefs. To support these patients through thrombocytopenia resulting from a variety of reasons including stem cell transplant, bleeding complications and surgical blood loss, we administer aminocaproic acid by IV or PO in varied doses with Vitamin K subcutaneously at 10mg daily for 3 days. Oral use is preferred but the large doses we prescribe are difficult for many patients to tolerate in pill form. The standard dosing regimen for our bloodless stem cell patients is 24g in 24 hours, administered on a prophylactic basis to prevent bleeding when platelet count falls below 10,000cells/ μL. Using this approach in over 70 stem cell patients, we have not experienced any bleeding-related mortality and only one major intestinal bleeding episode. In addition, this combination is used to stop ongoing blood loss at doses that range from 500mg – 24g/day of aminocaproic acid. With our novel use of the dosing and combination of these drugs, we have experienced minimal drug-related toxicity. Though the label warns against a potential for muscle weakness and necrosis of skeletal muscle with prolonged administration and that rapid intravenous administration could lead to hypertension, bradycardia, or arrhythmia (package insert), our patients have not experienced any of these indicated adverse events. We have also experienced no thrombotic episodes other than one patient, treated for a life-threatening urologic bleed, who formed a clot in the bladder, which resolved without further complications. In addition to being an effective alternative to blood product support, the combination of aminocaproic acid and Vitamin K is cost effective and can be administered orally on an outpatient basis with acceptable toxicity, as demonstrated above. At approximately $500.00 for 100 of the 1000mg Amicar tablets, this drug is cost effective when compared to the average cost of a platelet transfusion. For our stem cell regimen, the daily cost of oral aminocaproic acid is about $120.00. In all patients, our average oral dose, administration length and cost, calculated over 25 courses between January 2007 and July 2008, was 11g/day for 3 days at approximately $55.00/ day. Considering the cost, complications, and risks associated with platelet transfusions, the favorable outcomes we have seen with our use of aminocaproic acid and Vitamin K suggest that this drug could be an alternative or adjunct therapy to provide hemostasis in a wide variety of patients with thrombocytopenia, platelet refractoriness and bleeding.
The prevalence of asthma in humans is increased in females compared to males after puberty, but the reasons for this remain unclear. The rare type 2 innate lymphoid cells (ILC2) have been recently implicated as drivers of allergic asthma. The objective of this study was to investigate sex differences in an experimental murine model with a focus on sex-specific ILC2 effects. METHODS: Male and female BALB/c mice were sensitized and subsequently challenged with aerosolized ovalbumin (OVA) on days 17-21 for serum, bronchoalveolar lavage fluid (BALF), and lung tissue collection, and challenged for an additional 5 days for airway hyper-responsiveness (AHR). RESULTS: As compared to saline, OVA challenged mice demonstrated increased serum OVA-IgE, AHR, levels of type 2 cytokines (IL-4, IL-5, IL-13), and cellular influx of eosinophils, B cells, dendritic cells, T cells, and ILC2. Sex differences were demonstrated such that female mice had increased serum OVA-specific IgE, lung nitric oxide levels, and AHR as compared to males. As compared to male mice, dendritic cells were decreased in BALF and B cells were increased in the BALF and lung tissues of OVA challenged females. Female OVA challenged mice also demonstrated lower frequency of ILC2 in BALF, yet increased frequency in whole lung tissue. There was a significant increase in the levels of IL-5 and IL-13 produced ex vivo by IL-33 stimulated, isolated lung ILC2 from female saline and OVA challenged mice as compared to males. CONCLUSIONS: Taken together, the study highlights a potential sexspecific difference in ILC2 localization and activation in experimental allergic asthma.
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