Transition mutation in codon 248 of the p53 tumor suppressor gene induced by reactive oxygen species and a nitric oxide-releasing compound.

Exposing the human bronchial epithelial cell line BEAS-2B to the nitric oxide (NO) donor sodium 1-(N,N-diethylamino)diazen-1-ium-1, 2-diolate (DEA/NO) at an initial concentration of 0.6 mM while generating superoxide ion at the rate of 1 microM/min with the hypoxanthine/xanthine oxidase (HX/XO) system induced C:G-->T:A transition mutations in codon 248 of the p53 gene. This pattern of mutagenicity was not seen by 'fish-restriction fragment length polymorphism/polymerase chain reaction' (fish-RFLP/PCR) on exposure to DEA/NO alone, however, exposure to HX/XO led to various mutations, suggesting that co-generation of NO and superoxide was responsible for inducing the observed point mutation. DEA/NO potentiated the ability of HX/XO to induce lipid peroxidation as well as DNA single- and double-strand breaks under these conditions, while 0.6 mM DEA/NO in the absence of HX/XO had no significant effect on these parameters. The results show that a point mutation seen at high frequency in certain common human tumors can be induced by simultaneous exposure to reactive oxygen species and a NO source.

Cost-effectivness in a DRG system for two-step exchange of infected total joint arthroplasty

The costs related to the treatment of infected total joint arthroplasties represent an ever groving burden to the society. Different patient-adapted therapeutic options like débridement and retention, 1- or 2-step exchange can be used. If a 2-step exchange is used we have to consider short (2-4 weeks) or long (>4-6 weeks) interval treatment. The Swiss DRG (Diagnose related Groups) determines the reimboursement the hopsital receives for the treatment of an infected total arthroplasty. The review assesses the cost-effectiveness of hospitalisation practices linked to surgical treatment in the two-stage exchange of a prosthetic-joint infection. The aim of this retrospectiv study is to compare the economical impact between a short (2 to 4 weeks) versus a long (6 weeks and above) interval during a two-satge procedure to determine the financial impact. Retrospectiv study of the patients with a two-stage procedure for a hip or knee prosthetic joint infection at CHUV hospital Lausanne (Switzerland) between 2012 and 2013. The review analyses the correlation between the interval length and the length of the hospital stay as well as with the costs and revenues per hospital stay. In average there is a loss of 40′000 Euro per hospitalisation for the treatment of prosthetic joint infection. Revenues never cover all the costs, even with a short interval procedure. This economical loss increases with the length of the hospital stay if a long-term intervall is choosen. The review explores potential for improvement in reimbourement practices and hospitalisation practices in the current Swiss healthcare setting. There should be alternative setups to decrease the burden of medical costs by a) increase the reimboursment for the treatment of infected total joints or by b) splitting the hospital stay with partners (rapid transfer after first operation from center hospital to level 2 hospital and retransfer for second operation to center) in order to increase revenues.

Les vaccins contre le zona : efficacité, sécurité, et rapport coût/bénéfices [Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

CONTEXT: A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. OBJECTIVE: To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. DOCUMENTARY SOURCE: Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". SELECTION OF STUDIES: Randomized and observational studies published in English and French language have been selected by two readers. RESULTS: On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. LIMITATION OF THE WORK: Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. CONCLUSION: Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will beneficiate the most of the vaccination has been identified yet and only an age criteria has been considered for the recommendation.

Air services on thin routes : Regional versus low-cost airlines

An examination of the impact in the US and EU markets of two major innovations in the provision of air services on thin routes - regional jet technology and the low-cost business model - reveals significant differences. In the US, regional airlines monopolize a high proportion of thin routes, whereas low-cost carriers are dominant on these routes in Europe. Our results have different implications for business and leisure travelers, given that regional services provide a higher frequency of flights (at the expense of higher fares), while low-cost services offer lower fares (at the expense of lower flight frequencies).

Gestión centralizada de dispositivos electrónicos low-cost para su uso en entornos domésticos

Este proyecto pretende implementar una solución de domótica reutilizando equipos de bajo coste disponibles en una vivienda que son gestionados de forma independiente y carecen de protocolos de comunicaciones estandarizados para su interconexión con otros entornos.

Prediction of the economic cost of individual long-term care in the Spanish population

Pensions together with savings and investments during active life are key elements of retirement planning. Motivation for personal choices about the standard of living, bequest and the replacement ratio of pension with respect to last salary income must be considered. This research contributes to the financial planning by helping to quantify long-term care economic needs. We estimate life expectancy from retirement age onwards. The economic cost of care per unit of service is linked to the expected time of needed care and the intensity of required services. The expected individual cost of long-term care from an onset of dependence is estimated separately for men and women. Assumptions on the mortality of the dependent people compared to the general population are introduced. Parameters defining eligibility for various forms of coverage by the universal public social care of the welfare system are addressed. The impact of the intensity of social services on individual predictions is assessed, and a partial coverage by standard private insurance products is also explored. Data were collected by the Spanish Institute of Statistics in two surveys conducted on the general Spanish population in 1999 and in 2008. Official mortality records and life table trends were used to create realistic scenarios for longevity. We find empirical evidence that the public long-term care system in Spain effectively mitigates the risk of incurring huge lifetime costs. We also find that the most vulnerable categories are citizens with moderate disabilities that do not qualify to obtain public social care support. In the Spanish case, the trends between 1999 and 2008 need to be further explored.

Price rivalry in airline markets: A study of a successful strategy of a network carrier against a low-cost carrier

Competition in airline markets may be tough. In this context, network carriers have two alternative strategies to compete with low-cost carriers. First, they may establish a low-cost subsidiary. Second, they may try to reduce costs using the main brand. This paper examines a successful strategy of the first type implemented by Iberia in the Spanish domestic market. Our analysis of data and the estimation of a pricing equation show that Iberia has been able to charge lower prices than rivals with its low-cost subsidiary. The pricing policy of the Spanish network carrier has been particularly aggressive in less dense routes and shorter routes.

Cost-minimization analysis of three decision strategies for cardiac revascularization : results of the "suspected CAD"cohort of the european cardiovascular magnetic resonance registry.

BACKGROUND: Coronary artery disease (CAD) continues to be one of the top public health burden. Perfusion cardiovascular magnetic resonance (CMR) is generally accepted to detect CAD, while data on its cost effectiveness are scarce. Therefore, the goal of the study was to compare the costs of a CMR-guided strategy vs two invasive strategies in a large CMR registry. METHODS: In 3'647 patients with suspected CAD of the EuroCMR-registry (59 centers/18 countries) costs were calculated for diagnostic examinations (CMR, X-ray coronary angiography (CXA) with/without FFR), revascularizations, and complications during a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive CXA and revascularization at the discretion of the treating physician (=CMR + CXA-strategy). In the hypothetical invasive arm, costs were calculated for an initial CXA and a FFR in vessels with ≥50 % stenoses (=CXA + FFR-strategy) and the same proportion of revascularizations and complications were applied as in the CMR + CXA-strategy. In the CXA-only strategy, costs included those for CXA and for revascularizations of all ≥50 % stenoses. To calculate the proportion of patients with ≥50 % stenoses, the stenosis-FFR relationship from the literature was used. Costs of the three strategies were determined based on a third payer perspective in 4 healthcare systems. RESULTS: Revascularizations were performed in 6.2 %, 4.5 %, and 12.9 % of all patients, patients with atypical chest pain (n = 1'786), and typical angina (n = 582), respectively; whereas complications (=all-cause death and non-fatal infarction) occurred in 1.3 %, 1.1 %, and 1.5 %, respectively. The CMR + CXA-strategy reduced costs by 14 %, 34 %, 27 %, and 24 % in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59 %, 52 %, 61 % and 71 %, respectively, versus the CXA-only strategy. In patients with typical angina, cost savings by CMR + CXA vs CXA + FFR were minimal in the German (2.3 %), intermediate in the US and Swiss (11.6 % and 12.8 %, respectively), and remained substantial in the UK (18.9 %) systems. Sensitivity analyses proved the robustness of results. CONCLUSIONS: A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. However, in the subgroup of patients with typical angina, cost savings were only minimal to moderate.

Cost-benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost-effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. METHODS: ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS-specific costs were integrated into the model. RESULTS: The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre-ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS-specific costs were euro922 per patient. Mean total costs were euro56 083 per patient in the ERAS group and euro63 821 per patient in the pre-ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were euro9139 and euro13 793 per patient for the ERAS and pre-ERAS groups respectively (P = 0·151). CONCLUSION: ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.

Sex- and melanism-specific variations in the oxidative status of adult tawny owls in response to manipulated reproductive effort.

Oxidative stress, determined by the balance between the production of damaging reactive oxygen species (ROS) and antioxidant defences, is hypothesized to play an important role in shaping the cost of reproduction and life history trade-offs. To test this hypothesis, we manipulated reproductive effort in 94 breeding pairs of tawny owls (Strix aluco) to investigate the sex- and melanism-specific effects on markers of oxidative stress in red blood cells (RBCs). This colour polymorphic bird species shows sex-specific division of labour and melanism-specific history strategies. Brood sizes at hatching were experimentally enlarged or reduced to increase or decrease reproductive effort, respectively. We obtained an integrative measure of the oxidative balance by measuring ROS production by RBCs, intracellular antioxidant glutathione levels and membrane resistance to ROS. We found that light melanic males (the sex undertaking offspring food provisioning) produced more ROS than darker conspecifics, but only when rearing an enlarged brood. In both sexes, light melanic individuals had also a larger pool of intracellular antioxidant glutathione than darker owls under relaxed reproductive conditions (i.e. reduced brood), but not when investing substantial effort in current reproduction (enlarged brood). Finally, resistance to oxidative stress was differently affected by the brood size manipulation experiment in males and females independently of their plumage coloration. Altogether, our results support the hypothesis that reproductive effort can alter the oxidative balance in a sex- and colour-specific way. This further emphasizes the close link between melanin-based coloration and life history strategies.

Pedaling rate is an important determinant of human oxygen uptake during exercise on the cycle ergometer.

Estimation of human oxygen uptake (V˙o2) during exercise is often used as an alternative when its direct measurement is not feasible. The American College of Sports Medicine (ACSM) suggests estimating human V˙o2 during exercise on a cycle ergometer through an equation that considers individual's body mass and external work rate, but not pedaling rate (PR). We hypothesized that including PR in the ACSM equation would improve its V˙o2 prediction accuracy. Ten healthy male participants' (age 19-48 years) were recruited and their steady-state V˙o2 was recorded on a cycle ergometer for 16 combinations of external work rates (0, 50, 100, and 150 W) and PR (50, 70, 90, and 110 revolutions per minute). V˙o2 was calculated by means of a new equation, and by the ACSM equation for comparison. Kinematic data were collected by means of an infrared 3-D motion analysis system in order to explore the mechanical determinants of V˙o2. Including PR in the ACSM equation improved the accuracy for prediction of sub-maximal V˙o2 during exercise (mean bias 1.9 vs. 3.3 mL O2 kg(-1) min(-1)) but it did not affect the accuracy for prediction of maximal V˙o2 (P > 0.05). Confirming the validity of this new equation, the results were replicated for data reported in the literature in 51 participants. We conclude that PR is an important determinant of human V˙o2 during cycling exercise, and it should be considered when predicting oxygen consumption.

The economic cost of hospital malnutrition in Europe; a narrative review

Background: Malnutrition among hospitalized patients increases length of stay (LOS) and carries extra hospitalization costs. Objective: To review the impact of malnutrition on hospital LOS and costs in Europe. Methods: PubMed and Google Scholar search. All articles from January 2004 until November 2014 were identified. Reference lists of relevant articles were also manually searched. Results: Ten studies on LOS and nine studies on costs were reviewed. The methods used to assess malnutrition and to calculate costs differed considerably between studies. Malnutrition led to an increased LOS ranging from 2.4 to 7.2 days. Among hospitalized patients, malnutrition led to an additional individual cost ranging between 1640 V and 5829 V. At the national level, the costs of malnutrition ranged between 32.8 million V and 1.2 billion V. Expressed as percentage of national health expenditures, the values ranged between 2.1% and 10%. Conclusions: In Europe, malnutrition leads to an increase in LOS and in hospital costs, both at the individual and the national level. Standardization of methods and results reported is needed to adequately compare results between countries. © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

The use of cost per life year gained as a measurement of cost-effectiveness in Spain: a systematic review of recent publications

The objective of this study was to evaluate the methodological characteristics of cost-effectiveness evaluations carried out in Spain, since 1990, which include LYG as an outcome to measure the incremental cost-effectiveness ratio. METHODS: A systematic review of published studies was conducted describing their characteristics and methodological quality. We analyse the cost per LYG results in relation with a commonly accepted Spanish cost-effectiveness threshold and the possible relation with the cost per quality adjusted life year (QALY) gained when they both were calculated for the same economic evaluation. RESULTS: A total of 62 economic evaluations fulfilled the selection criteria, 24 of them including the cost per QALY gained result as well. The methodological quality of the studies was good (55%) or very good (26%). A total of 124 cost per LYG results were obtained with a mean ratio of 49,529 and a median of 11,490 (standard deviation of 183,080). Since 2003, a commonly accepted Spanish threshold has been referenced by 66% of studies. A significant correlation was found between the cost per LYG and cost per QALY gained results (0.89 Spearman-Rho, 0.91 Pearson). CONCLUSIONS: There is an increasing interest for economic health care evaluations in Spain, and the quality of the studies is also improving. Although a commonly accepted threshold exists, further information is needed for decision-making as well as to identify the relationship between the costs per LYG and per QALY gained.