Using an economic simulation model to identify key drivers of profitability and estimate the environmental sustainability impact of immunization against gonadotropin-releasing factor (GnRF) in male and female pigs intended for market.

An existing model was used to identify key drivers of profitability and estimate the impact on environmental sustainability when immunizing finishing pigs against GnRF with Improvac®. The model estimated performance and economic differences between immunized (IM) and non-IM pigs from the perspective of producers and packers, based on two recent meta-analyses in male and female pigs. It was populated with data from 9 countries in four continents (Europe, Asia, North and Latin-America). One-way sensitivity analyses (OWSA) were used to define key drivers of profitability. When changing the country specific input data over a range of ±20%, most OWSA did not reverse the mathematical sign of incremental net return between IM and non-IM pigs as calculated in base case analyses. Only the difference in feed conversion rate between IM and untreated female pigs was a key driver of profitability. The parameters with the highest impact on outcomes were similar across countries and expectable (feed costs), or explainable (parameters with statistical differences between IM and non-IM pigs in meta-analyses). In both single-gender herds, Improvac® reduced the environmental impact of pig production by improving feed efficiency (FE), the key driver of environmental burden. In a 50/50 mixed gender herd, IM pigs consumed less feed and gained more weight in 7 out of 9 countries; in the other two countries the FE calculated for the additional weight gain in IM pigs was >1.00, i.e., each additional kilogram of weight gain was associated with less than one additional kilogram of feed consumed.

Immunization against gonadotropin-releasing factor (GnRF) in market gilts: Effect on growth and carcass parameters, and impact of immunization timing.

Reproductive cycling in fattening gilts can be associated with undesirable effects, such as estrus-related aggressive behavior, reduced feed intake and, in production systems where gilts are co-housed with entire males, unwanted pregnancy. Immunization against Gonadotrophin Releasing Factor (IM) can temporarily suppress ovarian activity, including related negative consequences on animal welfare and productivity. Feed intake has been shown to be higher after IM, resulting in both increased growth and increased carcass fat. A series of studies was conducted to confirm these effects on production and look at their dynamics over time. Three trials were performed to a similar design, each involving 240 gilts divided into 4 experimental groups at 12 weeks of age. One group remained untreated while the others had the two dose, IM course completed 8, 6 or 4 weeks before harvest, which was on a single day at 24, 25 or 26 weeks of age depending on the study. Feed intake was measured daily and bodyweight weekly, allowing growth parameters to be calculated on a weekly basis and for specific longer periods. Carcass weight, backfat depth and lean meat percentage were recorded at harvest. No effects were observed before the second application of the immunological product (V2) and completion of the IM course. Starting in the second week after V2 all IM groups showed a marked and consistent increase in Average Daily Feed Intake (ADFI), typically peaking at over 120% of the control group 3 to 4 weeks after V2 and then slowly declining, but still remaining elevated at 8 weeks. Weekly Average Daily Gain (ADG) showed a similar pattern but with a faster decline, resulting in the initially favorable impact on feed efficiency becoming less favorable as the V2 to harvest interval (V2H) progressed. Carcass weights were higher in IM gilts and backfat depths were greater, with the effects increasing with increasing V2H. Correspondingly, carcass lean meat percentage tended to decrease, although the higher carcass weights meant that the absolute weight of lean meat remained similar or higher. Carcass yield was generally unaffected by IM, but some between-group differences were statistically significant, and it is possible that different factors predominated at different times after V2, creating a complex relationship with V2H duration. The optimum IM protocol will depend on local conditions and production objectives but, as a generalization and assuming ad libitum feeding, a shorter V2H will favor efficient growth, while a longer duration will maximize carcass changes, such as increased fat coverage. It is suggested that the growth performance changes seen after IM in gilts might be viewed as a process of adjustment to a heavier and fatter target body type.

The effect of immunization against gonadotropin-releasing factor on growth performance, carcass characteristics and boar taint relevant to pig producers and the pork packing industry: A meta-analysis.

Meta-analysis was used to compare pigs immunocastrated (IC) with Improvac® versus physically castrated (PC) or entire male (EM) pigs. Performance and carcass data as most relevant for producers and packers were analyzed and the risk of boar taint was assessed by comparing the number of pigs exceeding the consumer thresholds of detection (ToD) for skatole and androstenone. A total of 78 articles fulfilled pre-defined inclusion criteria. Compared to PC pigs, IC pigs have a higher average daily gain (ADG; +32.54 g/day, P < 0.0001) and more favorable feed conversion ratio (FCR; -0.234 kg/kg, P < 0.0001), higher live weight and percentage lean, and lower hot carcass weight (HCW) and dressing percentage. Compared to EM pigs, IC pigs have a higher ADG (+65.04 g/day, P < 0.0001), FCR (+0.075 kg/kg, P < 0.0001), live weight and HCW, and a similar dressing percentage. Conventionally raised IC pigs yield more valuable meat compared to PC (+0.628 kg) and EM (+1.385 kg) pigs. Heavy IC pigs (HCW > 97.7 kg) destined for the production of high-quality cured products gain approximately 0.3 kg more ham than their PC counterparts, with backfat and intramuscular fat still fulfilling the requirements for high-quality cured products. The risk of exceeding the ToD for skatole and androstenone is similar in IC and PC pigs, but significantly higher in EM pigs. Results from our meta-analyses confirm growth performance advantages of IC pigs compared with PC or EM pigs, and reveal a higher gain of valuable meat and a similar risk of boar taint as estimated for PC pigs.

Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational, and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer (AU)

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Evidence of clinical and economic impact of pharmacist interventions related to antimicrobials in the hospital setting.

The purpose of this paper was to review the literature regarding the clinical and economic impact of pharmacist interventions (PIs) related to antimicrobials in the hospital setting. A PubMed literature search from January 2003 to March 2016 was conducted using the terms pharmacist* or clinical pharmacist* combined with antimicrobial* or antibiotic* or anti-infective*. Comparative studies that assessed the clinical and/or economic impact of PIs on antimicrobials in the hospital setting were reviewed. Outcomes were classified as: treatment-related outcomes (TROs), clinical outcomes (COs), cost and microbiological outcomes (MOs). Acceptance of pharmacist recommendations by physicians was collected. PIs were grouped into patient-specific recommendations (PSRs), policy, and education. Studies' risk of bias was analyzed using Cochrane's tool. Twenty-three studies were evaluated. All of them had high risk of bias. The design in most cases was uncontrolled before and after. PSRs were included in every study; five also included policy and four education. Significant impact of PI was found in 14 of the 18 studies (77.8%) that evaluated costs, 15 of the 20 studies (75.0%) that assessed TROs, 12 of the 22 studies (54.5%) that analyzed COs, and one of the two studies (50.0%) that evaluated MOs. None of the studies found significant negative impact of PIs. It could not be concluded that adding other strategies to PSRs would improve results. Acceptance of recommendations varied from 70 to 97.5%. Pharmacists improve TROs and COs, and decrease costs. Additional research with a lower risk of bias is unlikely to change this conclusion. Future research should focus on identifying the most efficient interventions.

Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational, and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.

Pharmacokinetic monitoring of antiepileptic drugs.

Monitoring plasma levels of antiepileptic drugs for the treatment and prophylaxis of epilepsy is one of the strategies enabling clinical results to improve by reducing adverse affects and increasing effectiveness. The objective of this article is to review the basic aspects in the monitoring of antiepileptic drugs using a consensus document prepared and endorsed by the pharmacokinetics and pharmacogenetics working group (PK.gen) of the Sociedad Española de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacists).

Línea estratégica 5: Formación / No disponible

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In situ surface characterization and oxygen reduction reaction on shape-controlled gold nanoparticles.

Gold nanoparticles of different shapes/surface structures were synthesized and electrochemically characterized. An in-situ surface characterization of the Au nanoparticles, which was able to obtain qualitative information about the type and relative sizes of the different facets present in the surface of the Au nanoparticles, was carried out by using Pb Under Potential Deposition (UPD) in alkaline solutions as a surface sensitive tool. The results obtained show that the final atomic arrangement on the surface can be different from that expected from the bulk structure of the well-defined shape Au nanoparticles. In this way, the development of precise in-situ methods to measure the distribution of the different sites on the nanoparticle surface, as lead UPD on gold surfaces, is highlighted. Oxygen Reduction Reaction (ORR) was performed on the different Au nanoparticles. In agreement with the particular sensitivity of the oxygen reduction to the presence of Au(100) surface domains, cubic Au nanoparticles show much better electrocatalytic activity for ORR than small spherical particles and long nanorods, in agreement with the presence of a great fraction of (100) terrace sites on the surface of cubic gold nanoparticles.

LC method for the therapeutic drug monitoring of lamotrigine: evaluation of the assay performance and validation of its application in the routine area.

An accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of lamotrigine in human plasma has been developed and validated for use in pharmacokinetic studies. A validation strategy based on the accuracy profiles was used to select the most appropriate regression model and to determine the limits of quantitation as well as the concentration range. On the other hand, the present paper also shows this validation approach as a suitable tool to guaranty the quality of the results obtained by the use of the analytical validated methodology for plasma lamotrigine determination in a routine setting and to ensure the risk of obtaining the future measurements outside the previously fixed acceptance limits.

Shape-dependent electrocatalysis: methanol and formic acid electrooxidation on preferentially oriented Pt nanoparticles.

Reactivity towards methanol and formic acid electrooxidation on Pt nanoparticles with well characterised surfaces were studied and compared with the behaviour of single crystal electrodes with basal orientations. Polyoriented and preferential (100), (111) and (100)-(111) Pt nanoparticles were synthesised, cleaned preserving its surface structure, characterised and employed to evaluate the influence of the surface structure/shape of the Pt nanoparticles on these two relevant electrochemical reactions. The results pointed out that, in agreement with fundamental studies with Pt single crystal electrodes, the surface structure of the electrodes plays an important role on the reactivity of both oxidation processes, and thus the electrocatalytic properties strongly depend on the surface structure/shape of the nanoparticles, in particular on the presence of sites with (111) symmetry. These findings open the possibility of designing new and better electrocatalytic materials using decorated shape-controlled Pt nanoparticles as previously described with Pt single crystal electrodes.

Tellurium adatoms as an in-situ surface probe of (111) two-dimensional domains at platinum surfaces.

Irreversibly adsorbed tellurium has been studied as a probe to quantify ordered domains in platinum electrodes. The surface redox process of adsorbed tellurium on the Pt(111) electrode and Pt(111) stepped surfaces takes place around 0.85 V in a well-defined peak. The behavior of this redox process on the Pt(111) vicinal surfaces indicates that the tellurium atoms involved in the redox process are only those deposited on the (111) terrace sites. Moreover, the corresponding charge density is proportional to the number of sites on (111) ordered domains (terraces) that are, at least, three atoms wide. Hence, this charge density can be used to measure the number of (111) terrace sites on any given platinum sample. Structural information about tellurium adsorption is obtained from atomic-resolution STM images for the Pt(111) and Pt(10, 10, 9) electrodes. A rectangular structure (2 x radical 3) and a compact hexagonal structure (11 x 8) were identified. However, the redox peak for adsorbed tellurium on (100) domains at 1.03 V overlaps with peaks arising from steps and (110) sites. Therefore, it cannot be used without problems for the determination of (100) sites on a platinum sample. On the (100) terraces, the surface structure of the adsorbed tellurium is c(2 x 2), as revealed by STM. Finally, tellurium irreversible adsorption has been used to estimate the number of (111) ordered domains terrace sites on different polycrystalline platinum samples, and the results are compared to those obtained with bismuth irreversible adsorption.

Tegafur and 5-fluorouracil pelvic tissue concentrations in rectal cancer patients receiving preoperative chemoradiation.

BACKGROUND AND PURPOSE: To investigate the presence of 5-Fluorouracil (5-FU) in pelvic tissue after oral administration of tegafur. To measure tegafur and 5-FU concentrations in normal rectal mucosa, perirectal fat and residual tumor in rectal cancer patients receiving preoperative chemoradiation. To correlate drug concentrations with cancer downstaging effects. PATIENTS AND METHODS: Three tissue samples taken from 16 surgical specimens after recto-sigmoid resection were analyzed. Tegafur and 5-FU concentrations were measured using high-performance liquid chromatography. 16 patients with locally advanced rectal cancer were treated with preoperative pelvic irradiation (45-50 Gy) sensitized with oral tegafur (400 mg for every 8 hours daily). Seven patients received a precharge dose of tegafur (400 mg oral every 8 hours) 24 hours before surgery. RESULTS: In 8 of the 9 patients who did not receive a precharge dose, detectable levels of tegafur were observed in fat tissue, normal mucosa and tumor, but detectable 5-FU levels were only observed in one patient. Mean concentrations (ranges) for tegafur in fat, normal mucosa and tumor in patients without the precharge dose were 72.19 (12.1-205.6), 179.53 (11.30-727.7) and 252.35 (27.9-874.6) ng/g, respectively; mean concentrations for 5-FU in the same samples were 0.95, 1.92 and 2.68 ng/g (1 patient), respectively. In patients receiving a tegafur precharge, both tegafur and 5-FU were present in all tissue samples with the exception of 2 fat samples, in which drug concentrations were undetectable. 5-FU levels were higher in tumor than other sites, with a median value of 68.24 ng/g (range 3.8-283.05 ng/g). Tegafur levels were also higher in tumor samples than other sites (mean 3446.53 ng/g, range 1044.5-7847.0 ng/g), except in 2 patients who had higher levels of tegafur in normal mucosa. CONCLUSIONS: Tegafur and 5-FU are not always present in pelvic tissues 5 to 6 weeks after oral administration of tegafur. Both drugs were present in the tissues analyzed, in relevant concentrations, 24 hours after oral administration of tegafur. The data obtained suggest a tendency (not significant) toward a correlation between levels of 5-FU present in the residual tumor and cancer downstaging.

Characterization of a 20 kHz sonoreactor. Part I: analysis of mechanical effects by classical and numerical methods.

Numerical simulations have been carried out in order to characterize the ultrasonic field propagation and to obtain the spatial distribution of the mechanical effect derived from it. The results have been compared with those obtained with different classical physical methods (calorimetry, aluminium foil erosion, thermal probes) and have given useful information about the influence of the presence of probes and auxiliary tools in the ultrasonic field. All these information have been used for the development of the Part II of this work: analysis of chemical effects, providing an accurate picture of the reaction environment in the sonoreactor used (20 kHz, 100 W supplied by Undatim) for further uses in sonoelectrochemical studies.

Characterization of a 20 kHz sonoreactor. Part II: analysis of chemical effects by classical and electrochemical methods.

A new electrochemical redox probe has been investigated in order to characterize the local production of radicals during the cavitation events. The results have been compared with those obtained with Fe(CN)6(3-)/Fe(CN)6(4-) (electrochemical probe for local mechanical effects) and classical chemical methods such as iodide and Fricke dosimeters (chemical probes for global effects).

Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection.

Capecitabine (N4-pentoxycarbonyl-5'-deoxy-5-fluorocytidine, Xeloda), a prodrug of 5-fluorouracil (5-FU), is an oral tumor-selective fluoropyrimidine carbamate approved in the treatment of colorectal and breast cancer. It has a preferential activation to 5-FU by thymidine phosphorilase (TP) in target tumor tissues through a series of three metabolic steps minimizing the exposure of normal tissues to 5-FU. It offers the potential of less gastrointestinal toxicity and advantages in terms of convenience and quality of life for the patient, in addition to cost-effectiveness as compared with intravenous 5-FU chemotherapy. We developed a high performance liquid chromatography assay for the determination of plasma capecitabine and its nucleoside metabolite concentrations and 5-FU catabolite dihydro-5-fluorouracil in a single step extraction and a single HPLC injection. The retention times of dihydro-5-fluorouracil, 5-FU, 5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine were 3.6, 4.4, 11.4 and 20.4 min, respectively and the internal standard retention times were 8.7 and 12.2 min for 5-bromouracil (5-BU) and tegafur, respectively. The limit of detection was 0.01 microg/ml for capecitabine and its nucleoside metabolites and the limit of quantification was 0.025 microg/ml. Extraction efficiency was >80% with a single solvent mixture extraction step for all analytes of interest. The assay had good precision, the within-day and between-day standard deviation of the mean (R.S.D.) being <10% in the linear range 0.025-10 microg/ml. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of capecitabine and its metabolites.

Influence of chloride ion on electrochemical degradation of phenol in alkaline medium using bismuth doped and pure PbO2 anodes.

Electrochemical method at laboratory scale for the treatment of biorefractory solutions with high phenol content--1000 ppm is described. Total degradation of phenol was obtained at alkaline pH when NaCl was present using Bi-doped and pure lead dioxide electrodes. A filter press cell of 63 cm2 geometric area was used for this purpose. Measurements of chemical oxygen demand (COD), phenol, carbon monoxide, carbon dioxide, and volatile organic compounds (VOCs) have been used to characterise the electrochemical process for phenol elimination. It is worth noting that in the absence of NaCl, the charge efficiency of COD removal was independent of the current density in the range studied (50-100 mA cm(-2)) Moreover, when NaCl was present, the current efficiency for COD and phenol removal increase as the chloride concentration increases. Chloroform was the only halocompound detected at the end of reaction. For both electrodes, Bi-doped and pure lead dioxide, the chloroform concentration at the end of the electrolysis decreases, working at low current densities and for low chloride concentrations.

Separation methods for camptothecin and related compounds.

This paper reviews working procedures for the analytical determination of camptothecin and analogues. We give an overview of aspects such as the chemistry, structure-activity relationships, stability and mechanism of action of these antitumor compounds. The main body of the review describes separation techniques. Sample treatment and factors influencing high-performance liquid chromatography development are delineated. Published high-performance liquid chromatographic methods are summarized to demonstrate the variability and versatility of separation techniques and a critical evaluation of separation efficiency, detection sensitivity and specificity of these methods is reported.