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Stephen S Johnston,1 Nadine Jamous,2 Sameer Mistry,3 Simran Jain,4 Gaurav Gangoli,5 Walter Danker,5 Eric Ammann,6 Kingsley Hampton7 1Department of Epidemiology, Medical Devices, Johnson & Johnson, New Brunswick, NJ, USA; 2Department of Health Economics and Market Access, Johnson & Johnson Medical Ltd, Edinburgh, UK; 3Department of Medical Affairs, Johnson & Johnson Medical Ltd, Berkshire, UK; 4Department of Decision Science, Mu Sigma, Bangalore, India; 5Department of Health Economics and Market Access, Ethicon, Inc, Somerville, NJ, USA; 6Department of Epidemiology, Janssen, Titusville, NJ, USA; 7Department of Cardiovascular Science, University of Sheffield, Sheffield, UKCorrespondence: Stephen S JohnstonDepartment of Epidemiology, Medical Devices, Johnson & Johnson, 410 George Street, New Brunswick, NJ 08901, USATel +1-443-254-2222Email sjohn147@its.jnj.comPurpose: To evaluate the association of in-hospital surgical bleeding events with the outcomes of hospital length of stay (LOS), days spent in critical care, complications, and mortality among patients undergoing neoplasm-directed surgeries in English hospitals.Patients and Methods: This is a retrospective cohort study using English hospital discharge data (Hospital Episode Statistics [HES]) linked to electronic health records (Clinical Practice Research Datalink [CPRD]). HES includes information on patient demographics, admission and discharge dates, diagnoses and procedures, days spent in critical care, and discharge status. CPRD includes information on patient demographics, diagnoses and symptoms, drug exposures, vaccination history, and laboratory tests. Patients aged ≥ 18 years who underwent selected neoplasm-directed surgeries between 1-Jan-2010 and 29-February-2016: hysterectomy, low anterior resection (LAR), lung resection, mastectomy, and prostate surgery were included. The primary independent variable was in-hospital surgical bleeding events identified by diagnosis of haemorrhage and haematoma complicating a procedure or reopening/re-exploration and surgical arrest of postoperative bleeding. Outcomes included LOS, days spent in critical care, in-hospital complications (diagnoses of infections, acute renal failure, vascular events), and in-hospital mortality, identified during surgery through discharge. Multivariable regression was used to examine the adjusted association of bleeding events with outcomes.Results: The study included 26,437 neoplasm-directed surgeries (hysterectomy=6092; LAR=2957; lung=1538; mastectomy=12,806; prostate=3044). Incidence proportions of bleeding events were: hysterectomy=1.9% (95% confidence interval=1.1– 2.5%); LAR=3.0% (CI=2.3– 3.6%); lung=1.8% (CI=1.1– 2.5%); mastectomy=1.6% (CI=1.3– 1.8%); prostate=1.0% (CI=0.6– 1.3%). In adjusted analyses, bleeding events were associated with: prolonged LOS: 3.1 (CI=1.1– 6.3) mastectomy to 5.7 (CI=3.6– 8.2) LAR days longer; more days spent in critical care: 0.4 (CI=0.03– 0.27) mastectomy to 6.5 (CI=2.5– 13.6) hysterectomy days more; and higher incidence proportions of all examined complications; all P< 0.05.Conclusion: This study quantifies a substantial clinical and healthcare resource utilization burden associated with surgical bleeding among patients undergoing neoplasm-directed surgery in England hospitals.Keywords: hysterectomy, low anterior resection, lung resection, mastectomy, prostate surgery, hospital episode statistics admitted patient care database, clinical practice research datalink GOLD database

Enzymes immobilization is a useful way to allow enzyme reuse and increase their stability. A high redox potential laccase from Trametes versicolor ( TvL) and a low redox potential, but commercially available low-cost laccase from Myceliophthora thermophila ( MtL), were successfully immobilized and co-immobilized onto fumed silica nanoparticles (fsNP). Enzyme loads of 1.78 ± 0.07, 0.69 ± 0.03, and 1.10 ± 0.01 U/mg fsNP were attained for the optimal doses of TvL, MtL, and co-immobilized laccases, respectively. In general, the laccase-fsNP conjugates showed a higher resistance against an acidic pH value (i.e., pH 3), and a higher storage stability than free enzymes. In addition, immobilized enzymes exhibited a superior long-term stability than free laccases when incubated in a secondary effluent from a municipal wastewater treatment plant (WWTP). For instance, the residual activity after 2 weeks for the co-immobilized laccases and the mixture of free laccases were 40.2 ± 2.5 % and 16.8 ± 1.0 %, respectively. The ability of the laccase-fsNP to remove a mixture of C-bisphenol A (BPA) and C-sodium diclofenac (DCF) from spiked secondary effluents was assessed in batch experiments. The catalytic efficiency was highly dependent on both the microbial source and state of the biocatalyst. The high redox potential TvL in free form attained a four-fold higher percentage of BPA transformation than the free MtL. Compared to free laccases, immobilized enzymes led to much slower rates of BPA transformation. For instance, after 24 h, the percentages of BPA transformation by 1000 U/L of a mixture of free laccases or co-immobilized enzymes were 67.8 ± 5.2 and 27.0 ± 3.9 %, respectively. Nevertheless, the use of 8000 U/L of co-immobilized laccase led to a nearly complete removal of BPA, despite the unfavorable conditions for laccase catalysis (pH ~ 8.4). DCF transformation was not observed for any of the enzymatic systems, showing that this compound is highly recalcitrant toward laccase oxidation under realistic conditions. [ABSTRACT FROM AUTHOR]