Controversies in point-of-care 3D printing for oncological and reconstructive surgery with free software in oral and maxillofacial surgery: European regulations, costs, and timeframe.

The aim of this paper is to discuss the controversies surrounding the most recent European regulations, as well as the cost, for a 3D printing workflow using free-source software in the context of a tertiary level university hospital in the Spanish public health system. Computer-aided design and manufacturing (CAD/CAM) for head and neck oncological surgery with the printing of biomodels, cutting guides, and patient-specific implants has made it possible to simplify and make this type of highly complex surgery more predictable. This technology is not without drawbacks, such as increased costs and the lead times when planning with the biomedical industry. A review of the current European legislation and the literature on this subject was performed, and comparisons made with the authors' in-house 3D printing setup using free software and different 3D printers. The cost analysis revealed that for the cheapest setup with free software, it would be possible to amortize the investment from case 2, and in all cases the initial investment would be amortized before case 9. The timeframe ranged from 2 weeks with the biomedical industry to 72 h with point-of-care 3D printing. It is now possible to develop point-of-care 3D printing in any hospital with almost any budget.

Assessment of the occurrence and interaction between pesticides and plastic litter from vineyard plots.

In this research, aged plastic fragments collected from vineyards were characterized in terms of composition, residues of pesticides, and their potential to exchange these compounds with the aquatic media. To this end, we employed the qualitative and quantitative information provided by complementary analytical techniques, including chromatography, organic and inorganic mass spectrometry, infrared spectroscopy and electronic microscopy. Debris of weathered plastics were identified as polypropylene and polyethylene, containing different types of additives, from organic UV stabilizers to inorganic fillers, such as calcium salts. Regardless of polymer type, plastic litter collected from vineyards contained residues of pesticides, and particularly of fungicides, with total concentrations in the range of values from 114 ng g-1 to 76.4 µg g-1. Data obtained under different extraction conditions suggested that a fraction of these compounds was absorbed in aged polymers, penetrating inside the material. The parallel analysis of plastic litter and vineyard soils reflected higher pesticide residues in the former matrix. Furthermore, several fungicides, considered as labile in vineyard soils (i.e. zoxamide and folpet), were those showing the highest levels in plastic litter. Simulated sorption-desorption studies, with plastic debris in contact with surface water, demonstrated the higher affinity of aged materials by moderately polar pesticides than their new counterparts. For the first time, the manuscript highlights the presence of plastic litter in vineyards soils, reflecting the accumulation of several fungicides in this matrix, in some cases, with a different stability pattern to that observed in the soil from same vineyards.

Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe.

In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.

Occurrence and risk assessment of pesticides and pharmaceuticals in viticulture impacted watersheds from Northwest Spain.

An automated analytical methodology was developed, validated and applied to monitor 73 organic pollutants (pesticides and pharmaceuticals) in surface and groundwater samples obtained in watersheds from an intensive viticulture, rural region, in the Northwest of Spain. Filtered samples were concentrated using a reusable solid-phase extraction sorbent, on-line combined with liquid chromatography tandem mass spectrometry (LC-MS/MS). The analytical procedure achieved limits of quantification between 1 ng L-1 and 10 ng L-1, with a throughput of 2 samples hour-1, providing accurate recoveries for more than 90% of the 73 selected compounds, using calibration solutions prepared in ultrapure water (in presence of methanol and formic acid) as neat solvent. The distribution and the concentrations of pesticides in small streams impacted by discharges of treated municipal wastewaters were different in rural and residential areas. On the other hand, pharmaceuticals showed a similar distribution in both streams. In surface waters from viticulture impacted watersheds, with a limited influence of municipal wastewaters, pulses of pesticides were noticed, with values above 100 ng L-1 for several fungicides. Cardiovascular pharmaceuticals, psychiatric drugs and/or their transformation products were also ubiquitous in these samples, with low, but relatively stable concentrations among sampling campaigns. Within the suite of investigated compounds, maximum pesticide residues remained below their predicted-non effect concentration (PNEC) in all samples. On the other hand, the environmental concentrations of the cardiovascular drug olmesartan stayed systematically above its PNEC in fresh water samples.

Basic micro-pollutants in sludge from municipal wastewater treatment plants in the Northwest Spain: Occurrence and risk assessment of sludge disposal.

Sludge is one of the most problematic residues generated during wastewater treatment. Herein, we validate a single-step, sensitive procedure for the determination of a selection of 46 basic micro-pollutants, either used as pharmaceuticals or pesticides, in sludge from municipal sewage treatment plants (STPs), using liquid chromatography tandem mass spectrometry as determination technique. The proposed method permitted to achieve accurate recoveries (values from 70% to 120%, for samples spiked at different concentration levels) using solvent-based calibration standards. This feature, combined with limits of quantification lower than 5 ng g-1 (dry weight), allowed the rapid and sensitive quantification of target compounds in freeze-dried sludge samples. Out of 46 investigated pollutants, 33 species showed detection frequencies above 85% in a group of 48 sludge samples, obtained from 45 STPs located in the Northwest of Spain. The assessment of eco-toxicological risks associated to sludge disposal as fertilizer in agriculture and/or forestry, considering average concentrations found in sludge samples, highlighted eight pollutants (sertraline, venlafaxine, N-desethyl amiodarone, amiodarone, norsertraline, trazodone, amitriptyline and ketoconazole) representing an environmental hazard based on ratios between predicted soil levels and non-effect concentrations estimated using the equilibrium partition method.

Assessment of progesterone levels on the day of pregnancy test determination: A novel concept toward individualized luteal phase support.

Research question: The main objective of the study is to define the optimal trade-off progesterone (P4) values on the day of embryo transfer (ET), to identify low P4-human chorionic gonadotropin (hCG), and to establish whether P4 supplementation started on the hCG day can increase the success rate of the frozen embryo transfer (FET) cycle. Design: A single-center, cohort, retrospective study with 664 hormone replacement therapy (HRT)-FET cycles analyzed female patients who received vaginal 600 mg/day of P4 starting from 6 days before the FET, had normal P4 values on the day before ET, and whose P4 on the day of the pregnancy test was assessed. Results: Of the 664 cycles, 69.6% of cycles showed P4 ≥ 10.6 ng/ml, while 30.4% showed P4 < 10.6 ng/ml on the day of the hCG. Of the 411 chemical pregnancies detected, 71.8% had P4-hCG ≥ 10.6 ng/ml (group A), while 28.2% had P4-hCG < 10.6 ng/ml. Of the cycles with P4-hCG < 10.6 ng/ml, 64.7% (group B) were supplemented with a higher dose of vaginal P4 (1,000 mg/day), while 35.3% (group C) were maintained on the same dose of vaginal micronized P4. The live birth rate was 71.9%, 96%, and 7.3% for groups A, B, and C, respectively. Conclusion: The likelihood to detect P4-hCG < 10.6 ng/ml decreased as the level of serum P4 the day before ET increased. The live birth rate (LBR) was shown to be significantly lower when P4 was low and not supplemented.

Gender differences, inequalities and biases in the management of Acute Coronary Syndrome.

OBJECTIVE: The approach to Acute Coronary Syndrome from a gender perspective is relatively recent. Research is extensive at epidemiological and clinical levels. However, available evidence, besides neglecting the social dimensions of the disease, has made women invisible. The objective of this review was to analyze the inequalities and gender biases in Acute Coronary Syndrome, from the beginning of the disease process to the final resolution. METHODS: An exhaustive review of the literature of the entire health care process, from risk factors to rehabilitation and recovery, was carried out. The search for articles on gender, gender inequalities, or gender bias was conducted in indexed journals of social and health sciences. Also, a specific search was performed for each stage of the process, such as risk factors, prehospital phase, diagnosis, treatment, and rehabilitation. RESULTS: Results showed the presence of gender biases throughout the entire health care process in Acute Coronary Syndrome. It is shown gender inequalities in the access to medical care, including a poor recognition among women themselves as well as among health professionals; longer prehospital delays; inadequate diagnoses and treatments; or less assistance to cardiac rehabilitation programmes. These biases occurred at the different levels of the health services involved. Finally, this review included recommendations proposed or arising from the revised papers. CONCLUSIONS: Reducing gender biases in Acute Coronary Syndrome implies developing strategies to raise awareness among women, improve training of professionals serving at the different levels of health services, reduce delays, develop health management measures, and promote a research agenda.

Approaches to liquid chromatography tandem mass spectrometry assessment of glyphosate residues in wine.

The performance of two different analytical methodologies to investigate the presence of glyphosate (GLY) and aminomethylphosphonic acid (AMPA) residues in wine samples was evaluated. Transformation of compounds in their fluorene-9-methyloxycarbonyl derivatives permitted their separation under reversed-phase liquid chromatography with tandem mass spectrometry (LC-MS/MS) determination. Although the wine matrix severely impaired the efficiency of GLY derivatization, this drawback was solved using a molecularly imprinted sorbent for the previous, selective extraction of GLY and AMPA from wine. Alternatively, the use of a strong anionic exchange, polyvinyl alcohol-based LC column, turned to be the most effective alternative for direct determination of both compounds in diluted wine samples. The chromatographic behavior of this column and the magnitude of matrix effects observed during analysis of diluted wine samples were significantly affected by the composition of the mobile phase. Under final working conditions, this column permitted the separation of AMPA and the fungicide fosetyl (which shows common transitions in tandem MS/MS methods), it improved significantly the sample throughput versus extraction-derivatization-purification method, and it allowed the use of solvent-based calibration standards. Both analytical procedures provided similar limits of quantification (LOQs) for GLY (0.5-1.0 ng mL-1), while the multistep method was 8 times more sensitive to AMPA than the direct procedure. GLY residues stayed above method LOQs in 70% of the processed wines; however, concentrations measured in 95% of positive samples remained 100 times below the maximum residue limit (MRL) set for GLY in vinification grapes.

Assessment of direct analysis in real time accurate mass spectrometry for the determination of triclosan in complex matrices.

In this work, the applicability of direct analysis in real time coupled to accurate mass spectrometry (DART-MS) to the quantitative determination of triclosan (TCS) in samples with increasing complexity, from personal care products to extracts from sewage, is investigated. In the first term, DART-MS spectra of TCS as free phenol and as derivatized species are characterized; thereafter, the effects of several instrumental variables in the detectability of TCS (i.e., temperature, solvent, and compound holder) are discussed. Under final selected conditions, TCS was determined from its [M-H]- ions, without need of derivatization, attaining an instrumental limit of quantification of 5 ng mL-1, with a linear response range up to 1000 ng mL-1. Complex matrices, such as solid-phase extracts obtained from environmental water samples, moderately inhibited the ionization efficiency of TCS, with signal attenuation percentages in the range of 6 to 57%, depending on the sample type and on the concentration factor provided by the SPE procedure. The accuracy of results obtained by DART-MS was evaluated using liquid chromatography (LC) with MS detection; in both cases, a time-of-flight (TOF) MS instrument was employed for the selective determination of the [M-H]- ions of TCS (m/z values 286.9439 and 288.9410) using a mass window of 20 ppm. DART-MS did not only provide enough sensitivity to detect the presence of TCS in environmental samples (raw and treated wastewater as well as freeze-dried sludge), but also measured concentrations matched those determined by LC-ESI-TOF-MS, with only slightly higher standard deviations. During analysis of personal care products, containing much higher concentrations of TCS in a less complex matrix, both techniques were equivalent in terms of accuracy and precision. Graphical abstract.

Assessment of UV combined with free chlorine for removal of valsartan acid from water samples.

Valsartan acid (VALA) is a persistent and mobile pollutant, ubiquitously distributed in the aquatic environment. Herein, we assessed the efficiency of UV/free chlorine for the removal of this pollutant. Degradation experiments were performed using different water samples, considering several pH values and concentrations of inorganic anions. Time-course of VALA was measured by injection of different reaction time aliquots in a liquid chromatography (LC) triple quadrupole (QqQ) mass spectrometry (MS) system, whilst the study of potential transformation products (TPs) was evaluated by LC combined with a hybrid quadrupole time-of-flight (QTOF) MS system. Formation of volatile disinfection by-products (DBPs) was investigated by gas chromatography (GC) with TOF-MS detection. Compared to free chlorine treatment and UV photolysis, the combination of both parameters significantly enhanced the degradability of VALA. At neutral pH, UV/free chlorine was also more effective than UV/H2O2 to remove VALA from spiked water solutions. Three TPs of VALA were tentatively identified by LC-QTOF-MS, although only one was stable in the UV/free chlorine media. As regards volatile DBPs, the formation of chloroform, dichloroacetonitrile, di- and trichloroacetic acid was noticed. The mass yield of DBPs formation from VALA varied from 0.3% (dichloroacetonitrile) to 1.1% (chloroform). The efficiency of UV/free chlorine was first investigated in spiked solutions with increasing complexities: ultrapure, river and treated wastewater. Thereafter, the feasibility of reducing VALA levels in polluted river water was demonstrated.

Assessment of gas chromatography time-of-flight mass spectrometry for the screening of semi-volatile compounds in indoor dust.

Indoor dust contains a complex mixture of anthropogenic and synthetic compounds closely related to dermal and respiratory diseases. Target methods have been developed for the quantification of distinct groups of substances in dust samples; however, the comprehensive characterization of the different species existing in this matrix remains a challenging issue. Herein, we assess the performance of gas chromatography (GC) time-of-flight mass spectrometry (TOF-MS), using electron ionization (EI), for the screening of compounds present in indoor dust. Samples are processed by pressurized-liquid extraction (PLE) before GC-EI-TOF-MS analysis. The study proposes a data mining workflow for the non-target identification of species contained in dust extracts, aided by preliminary comparison with nominal resolution EI-MS spectra in the NIST17 library. The possibilities, and the limitations, of the above approach are discussed and the identities of >75 compounds are confirmed by comparison with authentic standards in dust from indoor environments. Some species, such as indigo, phthalic anhydride, 2,4-toluene di-isocyanate, phthalimide, certain UV absorbers and octyl isothiazolinone, identified in this research, have not been previously considered in target methods dealing with dust analysis. The study also evaluates two different algorithms for the suspected-target screening of dust extracts using a customized library of accurate EI-MS spectra. Finally, a semi-quantitative estimation of the range of concentrations for a group of 44 pollutants in a set of 27 dust samples is provided.

Free chlorine reactions of angiotensin II receptor antagonists: Kinetics study, transformation products elucidation and in-silico ecotoxicity assessment.

Angiotensin II receptor antagonists (ARA II) are widely employed in the treatment of hypertension-related diseases. Because of their partial metabolization and limited biodegradability, these drugs have become ubiquitous pollutants in the aquatic environment, including surface water. This research evaluated the reactivity of the ARA II drugs: irbesartan (IRB), losartan (LOS) telmisartan (TEL) and valsartan (VAL) with free chlorine. Responses of parent compounds and their transformation products (TPs) were followed by liquid chromatography (LC) with quadrupole (Q) time-of-flight (TOF) mass spectrometry. Degradation experiments were carried out using ultrapure and river water samples, adjusted at different pHs and, in some cases, adding a small amount (ng mL-1 level) of bromide salts. Whilst TEL and VAL remained stable in presence of relatively high concentrations of free chlorine (10 mg L-1), IRB and LOS were removed according to a pseudo-first order kinetics model. Considering an initial chlorine concentration of 10 mg L-1, their half-lives varied between 6 and 734 min, depending mostly on the water pH. IRB reacted with free chlorine through hydroxylation processes, with and without molecular cleavage and re-arrangements in the imidazolone ring. Its TPs showed a lower in-silico predicted toxicity than the parent drug. In case of LOS, two major competitive degradation routes were identified. They involved replacement of the methanol group attached to the imidazole cycle by chlorine or bromine, and the cleavage of this cycle with removal of the chlorinated carbon and the nitrogen in alpha position. The TPs generated following the first route are predicted to be more toxic than LOS.

Rectal culture-directed antibiotic prophylaxis before transrectal prostate biopsy: Reduced infectious complications and healthcare costs. / Profilaxis antibiótica «dirigida¼ por cultivos rectales antes de la biopsia prostática transrectal: reducción de complicaciones infecciosas y costes de atención sanitaria.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TUPB) is associated with infectious complications (ICs), which are related to a greater prevalence of ciprofloxacin-resistant bacteria (CRB) in rectal flora. We examined the ICs that occurred in 2 groups: A guided antibiotic prophylaxis (GP) group and an empiric prophylaxis (EP) group. We assessed the financial impact of GP. MATERIAL AND METHODS: The GP group was studied prospectively (June 2013 to July 2014). We collected rectal cultures (RCs) before the TUPB, which were seeded on selective media with ciprofloxacin to determine the presence of CRB. The patients with sensitive bacteria were administered ciprofloxacin. Patients with resistant bacteria were administered GP according to the RC antibiogram. The EP group was studied retrospectively (January 2011 to June 2009). RCs were not performed, and all patients were treated with ciprofloxacin as prophylaxis. The ICs in both groups were recorded during a period no longer than 30 days following TUPB (electronic medical history). RESULTS: Three hundred patients underwent TUPB, 145 underwent GP, and 155 underwent EP. In the GP group, 23 patients (15.86%) presented CRB in the RCs. Only one patient (0.7%) experienced a UTI. In the EP group, 26 patients (16.8%) experienced multiple ICs (including 2 cases of sepsis) (P<.005). The estimated total cost, including the management of the ICs, was €57,076 with EP versus €4802.33 with GP. The average cost per patient with EP was €368.23 versus €33.11 with GP. GP achieved an estimated total savings of €52,273.67. Six patients had to undergo GP to prevent an IC. CONCLUSIONS: GP is associated with a marked decrease in the incidence of ICs caused by CRB and reduced healthcare costs.

Cost-Effectiveness Methods and Newborn Screening Assessment.

Nowadays, health funding decisions must be supported by sound arguments in terms of both effectiveness and economic criteria. After more than half a century of newborn screening for rare diseases, the appropriate economic evaluation framework for these interventions is still challenging. The validity of standard methods for economic evaluation heavily relies on the availability of robust evidence, but collection of such evidence is precluded by the rareness of the conditions that may benefit from screening. Furthermore, there are a series of conceptual and methodological limitations that warrant further careful consideration when assessing the cost-effectiveness of newborn screening programs. In this chapter we provide a general overview of current economic evaluation methods and the challenges for their application to newborn screening programs.

Clinical and financial implications of disease-related malnutrition in a department of Internal Medicine: prospective cohort study. / Repercusiones clínicas y económicas de la desnutrición relacionada con la enfermedad en un servicio de Medicina Interna: estudio de cohortes prospectivas.

BACKGROUND: Disease-related malnutrition is a challenge for Spanish hospitals. Our objective was to assess the feasibility and importance of establishing a nutritional screening strategy in our community. PATIENTS AND METHODS: A prospective cohort study was conducted in a department of internal medicine for 3 months. The nutritional screening was conducted at admission and was repeated weekly using the Malnutrition Universal Screening Tool. We analysed the clinical data, mean stay and expenses. RESULTS: The study included 330 patients (53.9% men), with a mean age of 77.8 years. The mean stay was 7 days, and the Charlson comorbidity index was 5.4. At admission, the Malnutrition Universal Screening Tool detected 26.9% of patients with a risk of malnutrition. Eighteen percent of the patients with a good nutritional state developed malnutrition during the hospitalisation. The patients with initially severe malnutrition had a longer mean stay. The patients whose nutritional state worsened during the hospitalisation had a significantly longer stay (2.5 days) compared with those whose state did not worsen. These cases of malnutrition caused a cost overrun of €767 per hospitalisation (35% greater), which entailed a malnutrition-related excess expenditure of €646,419.93 annually in the studied department. The appropriate coding resulted in an increase in mean weight from 2.11 to 2.81, which represented €82,568.52 and has not been previously quantified. CONCLUSION: The high prevalence and clinical and financial implications of Disease-related malnutrition in patients hospitalised in internal medicine warrants establishing protocols for its early detection and treatment.

Osteoporosis Management in a Real Clinical Setting: Heterogeneity in Intervention Approach and Discrepancy in Treatment Rates when Compared with the NOGG and NOF Guidelines.

Objective: The National Osteoporosis Guideline Group (NOGG) proposes intervention thresholds that vary by age. Instead, the National Osteoporosis Foundation (NOF) proposes a fixed threshold for decision. The aim of the present study was to compare the actual therapeutic decisions taken in a routine clinical practice setting with those recommended by the NOF and NOGG guidelines. Material and methods: A cross-sectional study was conducted in individuals referred to a densitometric unit who were not receiving antiresorptive therapy. The absolute risk of major and hip fracture was calculated using the British formula provided by the FRAX® tool. NOGG and NOF guidelines' therapeutic intervention thresholds were used. Agreement was calculated using Cohen's kappa. Results: A total of 640 individuals were included, of which 95% were women, with a median age of 59.4 (IQR=14) years. 31.7% of subjects who were analyzed received treatment for osteoporosis. The type of treatment that was mainly prescribed (71.9%) consisted of bisphosphonates. When applying the NOGG criteria, treatment was recommended in 22.7% of cases; this percentage increased to 42.2% with the NOF guidelines. According to both guidelines, 20.4% of patients would not have received treatment. The concordance, expressed as the kappa index, was low; 0.25 (CI 95% 0.17-0.34) and 0.49 (CI 95% 0.42-0.55), with the NOGG and NOF, respectively. Conclusions: Important heterogeneity exists in the treatment of osteoporosis in real practice. The choice of guideline has a major impact on the proportion and selection of individuals recommended for treatment and, subsequently, on treatment-related expenditures.

Assessment of the effect of prolonged forced swimming on CD-1 mice sperm morphology with and without antioxidant supplementation.

As physical exercise has been shown to negatively affect sperm morphology, this study was undertaken to assess the effect of a 3-min forced swimming protocol during 50 days, with and without administration of antioxidants [N-acetylcysteine (NAC) and trans-resveratrol], on sperm morphology in CD-1 mice. Forty-four 13-week-old CD-1 mice were randomly allocated to four different groups: mice not submitted to exercise, control group (CG), mice submitted to swimming without administration of antioxidants (EX), mice submitted to swimming that received trans-resveratrol supplementation [exercise group (EX)+Resv] and mice submitted to swimming exercise that received NAC supplementation (EX+NAC). The EX showed 30.5% of spermatozoa with normal morphology, showing significant differences with regard to the CG, which showed 58.5%. The groups receiving antioxidant supplements showed significantly higher percentages of spermatozoa with normal morphology in comparison with the EX group (EX+Resv: 64.1%, EX+NAC: 48.2%). The imposed model of forced swimming caused alterations in sperm morphology. The antioxidants employed seem to be suitable antioxidants for avoiding exercise-associated sperm morphology anomalies in prolonged forced swimming exercise. Trans-resveratrol has proven to be more efficient for this purpose.

[Sustainability and excellence of the Catalan health system. New paradigms, challenges and responses]. / Sostenibilidad y excelencia del sistema sanitario catalán. Nuevos paradigmas, retos y respuestas.

The aim of a health system and the priority of any government is to anticipate problems before they appear, provide an innovative response to these new needs and healthcare models, improve access of the general public and patients to health care, especially care for the most vulnerable groups, improve healthcare results and implement the structural reforms necessary to maintain a viable and sustainable quality public healthcare system for everyone. In the current environment, health systems are facing new economic, demographic, care, social, technological and political paradigms to which health policy must respond. Faced with these challenges, health systems, especially in the case of Catalonia, are challenged to take decisions on how best to approach the implementation of structural reform designed to facilitate the necessary economic and fiscal sustainability in the service of fresh and innovative health policies and patient-centred care within a system marked by excellence and equity.

Cost-effectiveness of three echinocandins and fluconazole in the treatment of candidemia and/or invasive candidiasis in nonneutropenic adult patients.

OBJECTIVE: To estimate the cost-effectiveness of three echinocandins (anidulafungin, caspofungin, and micafungin) and generic fluconazole in the treatment of nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain. MATERIALS AND METHODS: A decision-tree model was applied. The success and safety (hepatic and renal adverse effects) of first-line treatments were obtained from meta-analyses and systematic reviews of clinical trials. In the case of failure, a second-line treatment (liposomal amphotericin B after the echinocandins, or one of the echinocandins after fluconazole) was administered. The duration of the treatments (14 days total) was established by a panel of clinical experts using the Delphi method and according to Infectious Diseases Society of America guidelines. The cost of the medications and renal toxicity were considered. Deterministic and probabilistic sensitivity analysis using Monte Carlo simulations were carried out. RESULTS: The total cost of the treatment of candidemia and/or invasive candidiasis with anidulafungin, caspofungin, micafungin, and fluconazole was €5,483, €5,968, €6,231, and €2,088, respectively. Anidulafungin was the dominant treatment (more effective, less expensive) compared to micafungin and caspofungin. The cost of achieving one more patient successfully treated with anidulafungin, caspofungin, and micafungin compared to fluconazole was €17,199, €23,962, and €27,339, respectively. The result remained stable, despite modification of the duration of the first-line and second-line treatments, as well as most of the dosing regimens. The probabilistic analysis also remained stable. CONCLUSION: In accordance with this economic study, anidulafungin would produce savings and would be the dominant treatment compared with micafungin and caspofungin in nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain.

Poly(ester-ether)s: III. assessment of cell behaviour on nanofibrous scaffolds of PCL, PLLA and PDX blended with amorphous PMeDX.

The aim of this paper is to investigate the physico-chemical properties, degradation behaviour and cellular response of electrospun fibre-scaffolds of semi-crystalline PCL, PLLA and PDX blended with amorphous poly(methyl dioxanone) (PMeDX). Electrospun PCL/PMeDX and PLLA/PMeDX blend mats in varying weight ratios of the two components were fabricated and their overall performance was compared with similar composition PDX/PMeDX scaffolds. DSC analysis showed almost no change in crystallization temperature of PCL with increasing PMeDX content and TGA showed a different degradation profile as PMeDX content increased. The appearance of two crystallization peaks for PLLA/PMeDX blends suggested stereocomplex formation. As noted from AFM images, addition of PMeDX caused a change in the width of the lamellae from 14.8 ± 2.9 nm in 100/0 mat to 32.0 ± 11.5 nm in 85/15 mat. Moreover, PCL/PMeDX blend mats show a significant drop in Young's modulus for 93/7, 90/10 and 85/15 compositions compared to 100/0 and 98/2. On the other hand, no clear trend in mechanical properties was observed for espun PLLA/PMeDX mats with increasing PMeDX content. Based on these analyses, it was concluded that PCL and PMeDX were immiscible while miscible blends were obtained with PLLA and PMeDX. Initial degradation of electrospun mats over a period of 5 weeks appears to occur via a surface erosion mechanism. In vitro cell culture studies using HDFs showed that the scaffolds were bioactive and a greater density of viable cells was noted on electrospun PCL/PMeDX and PLLA/PMeDX scaffolds compared to PCL and PLLA mats respectively. HDFs infiltrated through the entire thickness of espun 85/15 PLLA/PMeDX scaffold due to a combination of factors including morphology, porosity, surface characteristics and mechanical properties.