Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery.

BACKGROUND: Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. METHODS: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. RESULTS: A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). CONCLUSION: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.

Application of an empirical transport model to simulate retention of nanocrystalline titanium dioxide in sand columns.

Nanocrystalline titanium dioxide was injected into sand columns to simulate subsurface injection for creation of a permeable treatment barrier. Past usage of this material as an ex situ pilot scale treatment filter has shown that it has a high adsorption capacity for a number of heavy metals and therefore would be a good candidate for injection technology. Three suspension concentrations (50, 75 and 100 mg l(-1)) were pumped through packed sand columns at different flow velocities (3.0, 6.8 and 14.1 cm min(-1)). Little to no particles was detected in the effluent. Most of the nanoparticles remained in the sand columns, with an increasing then decreasing retained solids pattern. Application of a one-dimensional advection-dispersion flow model, that included two empirical kinetic terms to account for particle retention in the porous media, produced data fits that followed the general trend of the data, but did not truly capture the concentration maxima in the data sets. Discussion of these results highlights the limited ability of existing models to aid in predicting particle retention of non-ideal materials for engineering purposes.

Type 2 diabetes mellitus and heart failure.

Diabetes mellitus and heart failure are common comorbidities, and their prevalence has increased significantly over the past decade. We examined the relationships between diabetes and heart failure, the effect of commonly prescribed antidiabetic drugs on the development of heart failure, and the benefits and risks of recommended heart failure therapies in patients with diabetes. Compared with patients with heart failure who do not have diabetes, patients with both diabetes and heart failure have a poorer prognosis, including a 1.5-2-fold higher risk of mortality. Based on the results of randomized controlled trials, insulin and sulfonylureas do not appear to protect against or contribute to the development of new-onset heart failure, whereas metformin may modestly reduce the risk. The use of metformin in patients with established heart failure is controversial; retrospective analyses have shown that metformin may have a beneficial effect on outcomes, but there are no prospective, randomized clinical trials to support its use in this population. The thiazolidinediones, however, contribute to the development of heart failure and increase the risk of heart failure exacerbations particularly when used in combination with insulin. Recommendations for the treatment of symptomatic heart failure in patients with diabetes have been largely derived from post hoc analyses or preplanned subgroup analyses in landmark clinical trials. The data clearly support the use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for both the prevention and treatment of symptomatic heart failure in patients with diabetes. Despite concerns regarding the potential risks of beta-blockers in patients with diabetes, these drugs have a clear mortality benefit in patients with stages B and C heart failure. Therefore, patients with diabetes should not be denied beta-blocker therapy unless there is a clear contraindication. Likewise, aldosterone receptor antagonists should be added to standard therapies in patients with stages C and D heart failure. Future heart failure studies should include a sufficiently large diabetes cohort to conduct meaningful preplanned subgroup analyses that examine the effect of proposed treatments on both heart failure-related and diabetes-related outcomes.

Prevalence of anemia in clinic patients with heart failure and cost analysis of epoetin treatment.

STUDY OBJECTIVES: To determine the prevalence of anemia in an outpatient heart failure clinic, describe the type of anemia in patients treated there, and evaluate the potential costs associated with epoetin therapy in this cohort. DESIGN: Single-center, retrospective cohort analysis (part 1) and a literature-based economic decision analysis (part 2). DATA SOURCE: Medical records from a multidisciplinary, outpatient, heart failure clinic, and published hospitalization and drug-use data. PATIENTS: We evaluated 170 adults with chronic heart failure who were enrolled in the clinic and for whom at least one complete blood count was recorded between January 1, 2003, and April 15, 2006. MEASUREMENTS AND MAIN RESULTS: In part 1, demographic and clinical data were extracted from electronic medical records. The overall prevalence of anemia was 47.6% or 47.1%, as based on World Health Organization or National Kidney Foundation definitions, respectively. Normocytic anemia was characterized in 75.0% of patients. In part 2, heart failure hospitalization rates and costs, drug acquisition, and drug administration were estimated by using the published literature. In a hypothetical cohort of 100 patients with heart failure and comorbid anemia, the costs associated with outpatient epoetin and intravenous iron therapy exceeded savings in hospitalization costs by $83,070. Results of 1-way sensitivity analyses generally confirmed robustness of the model. CONCLUSION: Anemia is a common comorbidity in patients with chronic heart failure treated in the outpatient clinic. Although the current evidence is insufficient to support the use of epoetin in this population, initial findings indicate that epoetin and intravenous iron therapy may be associated with positive clinical outcomes. From a pharmacoeconomic standpoint, however, a reduction in the cost of heart failure-related hospitalization does not offset the cost of epoetin and intravenous iron therapy.

Removal of depleted uranium from contaminated soils.

Contamination of soil and water with depleted uranium (DU) has increased public health concerns due to the chemical toxicity of DU at elevated dosages. For this reason, there is great interest in developing methods for DU removal from contaminated sources. Two DU laden soils, taken from U.S. Army sites, were characterized for particle size distribution, total uranium concentration and removable uranium. Soil A was found to be a well graded sand containing a total of 3210 mg/kg DU (3.99 x 10(4) Bq/kg, where a Becquerel (Bq) is a unit of radiation). About 83% of the DU in the fines fraction (particle diameter <0.075 mm, total DU 7732 mg/kg (9.61 x 10(4) Bq/kg)) was associated with the carbonate, iron and manganese oxide and organic matter fractions of the material. Soil B was classified as a sandy silt with total DU of 1560 mg/kg (1.94 x 10(4) Bq/kg). The DU content in the fines fraction was 5171 mg/kg (6.43 x 10(4) Bq/kg). Sequential extraction of the Soil B fines fraction indicated that 64% of the DU was present either as soluble U(VI) minerals or as insoluble U(IV). Citric acid, sodium bicarbonate and hydrogen peroxide were used in batch experiments to extract DU from the fines fraction of both soils. Citric acid and sodium bicarbonate were relatively successful for Soil A (50-60% DU removal), but not for Soil B (20-35% DU removal). Hydrogen peroxide was found to significantly increase DU extraction from both soils, attaining removals up to 60-80%.

Infertility, blood mercury concentrations and dietary seafood consumption: a case-control study.

OBJECTIVE: To compare blood mercury concentrations of infertile couples with those of fertile couples in Hong Kong, and to examine the relationship between blood mercury concentrations and seafood consumption. DESIGN: Case-control study. SETTING: In vitro fertilisation (IVF) Unit and Antenatal Unit of a university teaching hospital. Sample One hundred fifty-seven infertile couples attending IVF treatment and 26 fertile couples attending antenatal care without known occupational exposure to mercury. METHODS: Mercury concentrations in whole blood were measured by cold vapour atomic absorption spectrophotometry. A dietitian recorded the quantity of seafood consumption among infertile couples via a food-frequency questionnaire. Blood mercury concentrations and quantity of seafood consumption were compared between infertile and fertile couples. MAIN OUTCOME MEASURES: Whole blood mercury concentrations, quantity of seafood consumption. RESULTS: Infertile couples had higher blood mercury concentrations than fertile couples. 'Infertile males with abnormal semen' and 'infertile females with unexplained infertility' also had higher blood mercury concentrations than their fertile counterparts. Blood mercury concentrations were positively correlated with quantity of seafood consumption. Infertile subjects with elevated blood mercury concentrations consumed a larger amount of seafood. CONCLUSION: Higher blood mercury concentration is associated with male and female infertility. Higher seafood consumption is associated with elevated blood mercury concentrations in our infertile population.