Cost-Effectiveness of Cement Augmentation Versus No Augmentation for the Fixation of Unstable Trochanteric Fractures

Background:A previous randomized controlled trial (RCT) demonstrated a trend toward a reduced risk of implant-related revision surgery following fixation with use of a Proximal Femoral Nail Antirotation (PFNA) with TRAUMACEM V+ Injectable Bone Cement augmentation versus no augmentation in patients with unstable trochanteric fractures. To determine whether this reduced risk may result in long-term cost savings, the present study assessed the cost-effectiveness of TRAUMACEM V+ cement augmentation versus no augmentation for the fixation of unstable trochanteric fractures from the German health-care payer's perspective.Methods:The cost-effectiveness model comprised 2 stages: a decision tree simulating clinical events, costs, and utilities during the first year after the index procedure and a Markov model extrapolating clinical events, costs, and utilities over the patient's lifetime. Sources of model parameters included the previous RCT, current literature, and administrative claims data. Outcome measures were incremental costs (in 2020 Euros), incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model uncertainty was assessed with deterministic and probabilistic sensitivity analyses.Results:The base-case analysis showed that fixation with cement augmentation was the dominant strategy as it was associated with cost savings (50.3/patient) and QALY gains (0.01 QALY/patient). Major influential parameters for the ICER were the utility of revision, rates of revision surgery within the first year after fixation surgery, and the costs of augmentation and revision surgery. Probabilistic sensitivity analyses demonstrated that estimates of cost savings were more robust than those of increased QALYs (66.4% versus 52.7% of the simulations). For a range of willingness-to-pay thresholds from 0 to 50,000, the probability of fixation with cement augmentation being cost-effective versus no augmentation remained above 50%.Conclusions:Fixation with use of cement augmentation dominated fixation with no augmentation for unstable trochanteric fractures, resulting in cost savings and QALY gains. Given the input parameter uncertainties, future analyses are warranted when long-term costs and effectiveness data for cement augmentation are available.Level of Evidence:Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence

Healthcare resource use and costs related to surgical infections of tibial fractures in a Spanish cohort

Surgical site infection constitutes a serious complication in the healing process of bone fractures and has been associated with increases in medical resource use and healthcare costs. This study evaluates the economic impact of surgical site infection in tibial fractures in a Spanish cohort. It is a retrospective, single-centre, comparative cohort study of patients with tibial fractures with longitudinal follow-up for up to 18 months post-surgery. Included patients (n = 325) were adults, with tibial fracture, either isolated or polyfracture, or polytrauma with an Injury Severity Score >15. Patients had been surgically treated within 30 days of the tibial fracture by external or internal fixation, or external followed by internal fixation. Most patients (84.9%) had an American Society of Anaesthesiology score of 1–2. 20% of the patients had one open tibial fracture, 12.3% had polytrauma, and 20% had multiple fractures. Most patients were treated with a nail (41.8%) or a plate (33.8%). 56 patients (17.2%) developed surgical site infection. Patients with infection had significantly higher hospital length of stay (34.9 vs 12.0 days; p<0.001; +191%), readmissions (1.21 vs 0.25; p<0.001; +380%) and mean operating theatre time (499 vs 219 min; p<0.001; +128%) than patients without infection. Mean length of stay in intensive care did not significantly increase with infection (2.8 vs 1.7 days; p = 0.25). Total in-hospital costs for patients with infection increased from €7,607 to €17,538 (p<0.001; +131%). Overall, infections were associated with significantly increased healthcare resource use and costs. Preventive strategies to avoid infections could lead to substantial cost savings

RET PLCγ Phosphotyrosine Binding Domain Regulates Ca2+ Signaling and Neocortical Neuronal Migration

The receptor tyrosine kinase RET plays an essential role during embryogenesis in regulating cell proliferation, differentiation, and migration. Upon glial cell line-derived neurotrophic factor (GDNF) stimulation, RET can trigger multiple intracellular signaling pathways that in concert activate various downstream effectors. Here we report that the RET receptor induces calcium (Ca2+) signaling and regulates neocortical neuronal progenitor migration through the Phospholipase-C gamma (PLCγ) binding domain Tyr1015. This signaling cascade releases Ca2+ from the endoplasmic reticulum through the inositol 1,4,5-trisphosphate receptor and stimulates phosphorylation of ERK1/2 and CaMKII. A point mutation at Tyr1015 on RET or small interfering RNA gene silencing of PLCγ block the GDNF-induced signaling cascade. Delivery of the RET mutation to neuronal progenitors in the embryonic ventricular zone using in utero electroporation reveal that Tyr1015 is necessary for GDNF-stimulated migration of neurons to the cortical plate. These findings demonstrate a novel RET mediated signaling pathway that elevates cytosolic Ca2+ and modulates neuronal migration in the developing neocortex through the PLCγ binding domain Tyr1015

A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior

Hypocretin/orexin signaling is critically involved in relapse to drug-seeking behaviors. In this study, we investigated the involvement of the hypocretin system in the reinstatement of nicotine-seeking behavior induced by nicotine-associated cues. Pretreatment with the hypocretin receptor-1 antagonist SB334867, but not with the hypocretin receptor-2 antagonist TCSOX229, attenuated cue-induced reinstatement of nicotine-seeking, which was associated with an activation of hypocretin neurons of the lateral and perifornical hypothalamic areas. In addition, relapse to nicotine-seeking increased the phosphorylation levels of GluR2-Ser880, NR1-Ser890, and p38 MAPK in the nucleus accumbens (NAc), but not in the prefrontal cortex. Notably, phosphorylation levels of NR1-Ser890 and p38 MAPK, but not GluR2-Ser880, were dependent on hypocretin receptor-1 activation. The intra-accumbens infusion of the protein kinase C (PKC) inhibitor NPC-15437 reduced nicotine-seeking behavior elicited by drug-paired cues consistent with the PKC-dependent phosphorylations of GluR2-Ser880 and NR1-Ser890. SB334867 failed to modify cue-induced reinstatement of food-seeking, which did not produce any biochemical changes in the NAc. These data identify hypocretin receptor-1 and PKC signaling as potential targets for the treatment of relapse to nicotine-seeking induced by nicotine-associated cues.This work was supported by the Instituto de Salud Carlos III grants, #PI07/0559, #PI10/00316 and #RD06/001/001 (RTA-RETICS), by the Spanish Ministry of Science and Technology, Consolider-C #SAF2007-64062 and #SAF2011-29864, the Catalan Government (SGR2009-00731), and by the Catalan Institution for Research and Advanced Studies (ICREA Academia program). Ainhoa Plaza-Zabala and África Flores are recipients of a predoctoral fellowship from the Spanish Ministry of Educatio

Compressed fluids for food by-product biorefinery

Food industries produce annually billions of tons of wastes that have become a major concern worldwide. These residues can be valorized by different strategies leading to a sustainable utilization of feedstock. Thus, the biorefinery concept is a promising option to reduce environmental impact with an obvious economic advantage. Furthermore, the use of greener solvents in combination with compressed fluid technologies for biorefinery approaches has several favourable features involving less time, an enhancement of the extraction efficiencies and a reduction in the energy employed. The present chapter highlights the potential of biorefinery approaches based on compressed fluid technologies and gives an overview of their applications to obtain high added-value products from food residues. Combinations of compressed fluid technologies are reviewed always taking into account a green chemistry point of view.M.B. would like to acknowledge the Ministry of Economy and Competitiveness for the “Juan de la Cierva” postdoctoral grant FJCI-2016-30902 and project the support from the AGL2017-89417-R project.Peer reviewe