Antifungal prophylaxis in chemotherapy-associated neutropenia: a retrospective, observational study

<p>Abstract</p> <p>Background</p> <p>In August 2002, the antifungal prophylaxis algorithm for neutropenic hematology/oncology (NHO) patients at the Medical Center was changed from conventional amphotericin (AMB) to an azole (AZ) based regimen (fluconazole [FLU] in low-risk and voriconazole [VOR] in high-risk patients). The aim of our study was to compare outcomes associated with the two regimens, including breakthrough fungal infection, adverse drug events, and costs.</p> <p>Methods</p> <p>Adult, non-febrile, NHO patients who received prophylactic AMB from 8/01/01-7/30/02 or AZ from 8/01/02-7/30/03 were retrospectively evaluated.</p> <p>Results</p> <p>A total of 370 patients (AMB: n = 181; AZ: n = 216) associated with 580 hospitalizations (AMB: n = 259; AZ: n = 321) were included. The incidence of probable/definite breakthrough Aspergillus infections was similar among regimens (AMB: 1.9% vs AZ: 0.6%; p=0.19). A greater incidence of mild/moderate (24.7% vs. 5.3%; p < 0.0001) and severe renal dysfunction (13.5% vs. 4.4%; p < 0.0012) was observed with AMB. In contrast, patients treated with VOR were found to have an increased rate of severe hepatic toxicity (32.5%) compared with patients treated with either AMB (22.6%) or FLU (21.4%) (p = 0.05). While the AZ period was associated with a >$9,000 increase in mean total costs/hospitalization, the mean acquisition cost associated with AZ was only$947/hospitalization more than AMB.</p> <p>Conclusion</p> <p>While an AZ-based regimen is associated with increased cost, the reduced rate of nephrotoxicity and availability of oral dosage forms, suggests that azoles be used preferentially over AMB. However, an increased rate of severe hepatic toxicity may be associated with VOR.</p

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study.

BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake

Risk management and goal programming for feasible territorial investments

Urban rehabilitation through the redevelopment of public properties in disuse is among the main issues of the urban policies in the Euro area. However, since 2008, mainly due to the economic downturn, the enhancement of public properties has been characterized by a deadlock. Currently, the tendency in all European countries is to entrust the valorization of public buildings in disuse to new special entities, in terms of sales to third parties as well as rationalization for the economic management of the property. In this framework, this research aims to propose a decision support methodology for public and private subjects involved in the valorization of public properties. In particular, the developed model allows the assessment of the financial feasibility of the initiatives, in relation to the corresponding investment risks

Biological abnormality of impaired reading is constrained by culture

Developmental dyslexia is characterized by a severe reading problem in people who have normal intelligence and schooling. Impaired reading of alphabetic scripts is associated with dysfunction of left temporoparietal brain regions. These regions perform phonemic analysis and conversion of written symbols to phonological units of speech (grapheme-to-phoneme conversion); two central cognitive processes that mediate reading acquisition. Furthermore, it has been assumed that, in contrast to cultural diversities, dyslexia in different languages has a universal biological origin. Here we show using functional magnetic resonance imaging with reading-impaired Chinese children and associated controls, that functional disruption of the left middle frontal gyrus is associated with impaired reading of the Chinese language (a logographic rather than alphabetic writing system). Reading impairment in Chinese is manifested by two deficits: one relating to the conversion of graphic form (orthography) to syllable, and the other concerning orthography-to-semantics mapping. Both of these processes are critically mediated by the left middle frontal gyrus, which functions as a centre for fluent Chinese reading that coordinates and integrates various information about written characters in verbal and spatial working memory. This finding provides an insight into the fundamental pathophysiology of dyslexia by suggesting that rather than having a universal origin, the biological abnormality of impaired reading is dependent on culture.link_to_subscribed_fulltex