Impact of the COVID-19 pandemic in colorectal cancer diagnosis and presentation.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has been associated with a decrease in the colorectal cancer (CRC) incidence, due to the disruption of screening programmes and a downscaling of endoscopic activity. The endpoint of this study is to evaluate if the pandemic has led to a change in CRC diagnostic rate and presentation in our population. METHODS: Multicenter retrospective study of all public hospitals of the Aragon region, attending a population of 1,329,391 inhabitants. We have analyzed all CRC cases detected and endoscopic units workload the year before the pandemic onset (1 March 2019-14 March 2020) and the first year of the COVID-19 pandemic (15 March 2020-28 February 2021). RESULTS: The diagnosis of CRC cases dropped a 38.9% (888 pre-pandemic vs 542 pandemic cases). Also, there were 30.3% less colonoscopies performed (24,860 vs 17,337). During the pandemic, CRC cases were diagnosed in older patients (72.4±12.2 vs 71.2±12.1 years, p=0.021), and had more frequently severe complications at diagnosis (14.6% vs 10.4%, p=0.019). Moreover, most CRC cases were diagnosed in symptomatic patients (81.4%). No significant difference was found in CRC stage at diagnosis, although stage IV was more frequent (20.1% vs 16.1%). Most hospitals reported a lower workload of endoscopic activity. CONCLUSION: CRC diagnostic rate was lower after the onset of the pandemic. CRC was diagnosed in older patients and was more frequently associated with complications. After the onset of the pandemic, the endoscopic units did not reach the workload performed previously.

Analysing cross-cutting competencies learning in an online entrepreneurship context.

Research in teaching innovation encourages leveraging the evolution of digital technologies from using the device to learning with the device, which means a change from using information and communicational technologies to learning and knowledge technologies. Nevertheless, although the feasibility of implementing active and interactive methodologies to improve education is widely recognised, more research is needed to obtain evidence on the subjects and contents with the most significant potential for success. In addition, the most recent literature claims greater attention to the improvement of transversal skills, as they are critical in the student's professional future. Thus, the main objective of this study is to contribute to the development of immersive learning aimed at improving the cross-cutting skills of university students. Developing a teaching activity where the student acts as an entrepreneur in electronic distribution channels faces the research question. The student-company-university collaboration is the basis for enhancing the transversal skills of the Degree in Marketing and Market Research at the University of Zaragoza (Spain). The student participates in each step of the program as an active agent. The teacher tutors the work teams in each process step, and the Palbin Company provides the necessary technical support. The students give the information to analyse the success of the experience through two surveys -pre and post-workshop, following the methodology used in previous literature. While the activity planning is complex, the students show an excellent mood during the experience. The comparison between expectations and performance offers significant success from the student's point of view. As a result, the student improves cross-cutting competencies and gains confidence, satisfaction with their learning at university, and professional experience.

Bioaccumulation and biochemical responses in the peppery furrow shell Scrobicularia plana exposed to a pharmaceutical cocktail at sub-lethal concentrations.

Pharmaceutical drugs in the aquatic medium may pose significant risk to non-target organisms. In this study, the potential toxicity of a mixture of three compounds commonly detected in marine waters (ibuprofen, ciprofloxacin and flumequine) was assessed, by studying bioaccumulation, oxidative stress and neurotoxicity parameters (catalase CAT, superoxide dismutase SOD, glutathione reductase GR, glutathione S-transferase GST, lipid peroxidation LPO, glutathione peroxidase GPX, metallothionein MT and acetylcholinesterase AChE) in the clam Scrobicularia plana. Temporal evolution of selected endpoints was evaluated throughout an exposure period (1, 7 and 21 days) followed by a depuration phase. The accumulation of all drugs was fast, however clams showed the ability to control the internal content of drugs, keeping their concentration constant throughout the exposure and reducing their content after 7 days of depuration. The induction of biochemical alterations (SOD, CAT, LPO, MT, AChE) was observed in gills and digestive gland probably related to an imbalance in the redox state of clams as a consequence of the exposure to the drug mixture. These alterations were also maintained at the end of the depuration week when the high levels of SOD, CAT, GST and LPO indicated the persistence of oxidative stress and damage to lipids despite the fact that clams were no longer exposed to the mixture.

Monitoring of pharmaceuticals in aquatic biota (Procambarus clarkii) of the Doñana National Park (Spain).

In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over the 2011-2016 years period. Twenty-three selected pharmaceuticals (corresponding to eight therapeutic families) were evaluated in crayfish and water samples from Doñana National Park (Spain) (six sampling points selected in order to cover different possible pollution sources into and surrounding the Park). The multiresidue determination was carried out using enzymatic-microwave assisted extraction prior to high performance liquid chromatography mass spectrometry detection. Sulphonamides (sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole); trimethoprim, an antibiotic that is frequently co-administered with sulfamethoxazole; amphenicols (chloramphenicol, florfenicol and thiamphenicol); fluoroquinolones (ciprofloxacin, enrofloxacin, flumequine, danofloxacin, gatifloxacin, norfloxacin, marbofloxacin and grepafloxacin); penicillins (amoxicillin); tetracyclines (chlortetracycline and oxytetracycline); non-steroidal anti-inflammatory drugs (salicylic acid and ibuprofen); beta-blocker drugs (atenolol); and antiepileptics (carbamazepine) were analysed. Ciprofloxacin, ibuprofen, salicylic acid, flumequine, and carbamazepine were detected and/or quantified at some of the selected sampling points. A clear ecotoxicological risk to the ecosystem was demonstrated from the occurrence of ciprofloxacin in samples obtained after the punctual and massive presence of people inside the Park. Furthermore, flumequine and carbamazepine have been detected in Procambarus clarkii specimens in concentrations around 30 ng g-1 and 14 ng g-1, respectively, and their occurrence in the specimens could indicate the persistence of the discharge sources. The main source of pharmaceuticals into the Park might be the livestock farming activities, and the influence of urban wastewaters from surrounding villages does not seem to be very important.

Comparison of three electromembrane-based extraction systems for NSAIDs analysis in human urine samples.

A comparative study on the extraction efficiency of five non-steroidal anti-inflammatories was carried out using three different electromembrane extraction (EME) devices with different geometries. The employed setups were (a) a hollow fiber configuration (HF-EME), (b) a microfluidic device that allows working in semi-dynamic mode (µF-EME), and (c) a static miniaturized flat membrane device (FM-EME). Each system was applied to the extraction of salicylic acid (SAC), ketoprofen (KTP), naproxen (NAX), diclofenac (DIC), and ibuprofen (IBU) and subsequent determination by high-performance liquid chromatography with UV and fluorescence detection (HPLC/UV-DAD-FLD). Voltage, pH composition, and extraction time were optimized for all devices. Additionally, volume ratio was investigated for HF-EME and FM-EME and flow rate for the microfluidic device. HF-EME provides the best result in terms of sensitivity with a limit of detection (LOD) between 0.1 and 1.5 ng mL-1 for SAC and KTP, respectively, while LODs for µF-EME were between 100 ng mL-1 and 400 ng mL-1 for SAC and DIC, respectively; however, a lower amount of sample was required. Finally, the obtained results, in terms of enrichment factors and extraction recoveries, were discussed to establish the advantages and disadvantages of each device. The proposed EME methods were successfully applied to the determination of the target analytes in fortified human urine samples. Graphical abstract.

Electromembrane extraction for the determination of parabens in water samples.

To our knowledge, for the first time an electromembrane extraction combined with a high-performance liquid chromatography procedure using diode-array detection has been developed for the determination of five of the most widely used parabens: ethyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, isobutyl 4-hydroxybenzoate, and benzyl 4-hydroxybenzoate. Parabens were extracted from pH 4 aqueous sample solutions with use of an Accurel® S6/2 polypropylene hollow fiber that supports a liquid membrane of 1-octanol to a pH 12 aqueous acceptor solution placed inside the lumen of the hollow fiber. An electric current of 30 V was applied over the supported liquid membrane by means of platinum wires placed in the donor and acceptor phases. Parabens were extracted in 40 min with enrichment factors in the 30-49 range. The procedure has detection limits between 0.98 and 1.43 µg L(-1). The method was applied to the determination of parabens in surface environmental waters with excellent results.

[Analysis of 117 episodes of enterococcal bacteremia: Study of epidemiology, microbiology and antimicrobial susceptibility]. / Análisis de 117 episodios de bacteriemia por enterococo: estudio de la epidemiología, microbiología y sensibilidad a los antimicrobianos.

Enterococcal bacteremia has acquired considerable importance in recent years, mainly due to an increased number of cases that occur during hospital admission. We describe the episodes of enterococcal bacteremia in adult patients recorded at our hospital. Between January 2000 and December 2013, 117 episodes were analyzed. Sixty one percent (61%) of the patients were male and 39% female. The mean age was 68. Predisposing factors were present in 91% of patients. The primary source of infection was intraabdominal. Enterococcus faecalis was responsible for 65% of the cases; E. faecium for 28%; and other species for 7%. Thirty four percent (34%) of cases were polymicrobial bacteremia. All E. faecalis isolates were susceptible to ampicillin and vancomycin. Eighty eight percent (88%) of E. faecium were resistant to ampicillin and 54% to vancomycin and teicoplanin. In our hospital, Enterococcus is the sixth pathogen causing nosocomial bacteremia, with high incidence of ampicillin and vancomycin-resistant E. faecium.

Faculty versus students: different perceptions of misconducts at university.

Introduction: Academic integrity is a goal to be achieved by university institutions, and student academic behavioral misconduct is a phenomenon to be fought and eradicated. Two of the main problems faced by universities in this area are: (1) the lack of consensus among students and faculty on the seriousness of acts considered academic misconduct; and (2) the difficulty of noticing and controlling certain student behaviors. The main aim of this paper is to assess the importance of these two problems. Methods: For this purpose, the authors compare, on the one hand, students' and teachers' perceptions of the seriousness of different types of dishonest and inappropriate behaviors and, on the other hand, the frequency with which they report that these misconducts occur. Two samples were taken from the responses of students and teachers of the Economics and Business School of the University of Zaragoza. The first consisted of 333 students and the second of 72 teachers. The academic misconducts asked about were grouped into three categories: academic works, exams, and interpersonal relationships in the classroom. Nonparametric tests were used to study the significance of the differences observed in the responses of students and teachers. Results: Results show that the greatest differences in the assessment of the seriousness of academic misconducts are in the group referring to interpersonal relationships. In terms of frequency, the study reveals that there is a serious problem of moral hazard in some of the behaviors analyzed, since the frequency with which teachers notice these practices is lower than that expressed by students. Discussion: Based on these results, possible measures to be adopted in universities in order to eradicate the academic misconduct problem are discussed.

Chemical nature evolution of solid supports used in electromembrane extraction procedures: A comparative analysis based on metric tools.

BACKGROUND: In recent decades, green chemistry has been focusing on the adaptation of different chemical methods towards environmental friendliness. Sample preparation procedures, which constitute a fundamental step in analytical methodology, have also been modified and implemented in this direction. In particular, electromembrane extraction (EME) procedures, which have traditionally used plastic supports, have been optimized towards greener approaches through the emergence of alternative materials. In this regard, biopolymer-based membranes (such as agarose or chitosan) have become versatile and very promising substitutes to perform these processes. RESULTS: Different green metric tools (Analytical Eco-Scale, ComplexGAPI and AGREEprep have been applied to study the evolution of solid supports used in EME from nanostructured tissues and polymer inclusion membranes to agar films and chitosan flat membranes. The main goal is to evaluate the usage of these new biomaterials in the analytical procedure to quantify their environmental impact in the frame of Green Analytical Chemistry (GAC). In addition, both RGB model and BAGI metrics have been employed to study the sustainability of the whole procedure, including not only greenness, but also analytical performance and feasibility aspects. Results obtained after the performance of the mentioned metrics have demonstrated that the most efficient and environmentally friendly analytical methods are based on the use of chitosan supports. This improvement is mainly due to the chemical nature of this biopolymer as well as to the removal of organic solvents. SIGNIFICANCE: This work highlights the advantages of biodegradable materials employment in EME procedures to achieve green analytical methodologies. These materials also contribute to raise the figure of merits regarding to the quantification parameters in a wide range of applications compared to classical supports employed in EME, thus enhancing sustainability of procedures.

Electromembrane extraction (EME)--an easy, novel and rapid extraction procedure for the HPLC determination of fluoroquinolones in wastewater samples.

For the first time, an electromembrane extraction combined with a HPLC procedure using diode array and fluorescence detection has been developed for the determination of seven widely used fluoroquinolones (FQs): marbofloxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, gatifloxacin and grepafloxacin. The drugs were extracted from acid aqueous sample solutions (pH 5), through a supported liquid membrane consisting of 1-octanol impregnated in the walls of a S6/2 Accurel® polypropylene hollow fiber, to an acid (pH 2) aqueous acceptor solution inside the lumen of the hollow fiber. The main operational parameters were optimized, and extractions were carried out in 15 min using a potential of 50 V. Enrichment factors of 40-85 have been obtained using only 15 min of extraction time versus 330 min used in a previously proposed hollow-fiber liquid-phase microextraction procedure. The procedure allows low detection and quantitation limits of 0.005-0.07 and 0.007-0.15 µg L(-1), respectively. The proposed method was successfully applied to the FQs analysis in urban wastewaters.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

Green Method for the Selective Electromembrane Extraction of Parabens and Fluoroquinolones in the Presence of NSAIDs by Using Biopolymeric Chitosan Films.

A chitosan biopolymeric membrane was successfully used as a support in a green electromembrane extraction procedure for the simultaneous and selective extraction of seven parabens and three fluoroquinolones in the presence of three non-steroidal anti-inflammatory drugs. The optimal experimental conditions (10 mL donor phase and 50 µL acceptor phase, pH 10 in both phases; 80 V of applied voltage during 15 min of extraction time) were determined, providing high enrichment factors for six of the studied parabens (EF ≥ 90) and the three fluoroquinolones (EF ≥ 50). Wide linear concentration ranges (0.5-500 µg L-1), good linearity (>97%), low limits of detection (0.2-1.1 µg L-1), and good repeatability (relative standard deviation values 4-10%) were achieved. The proposed method was successfully applied for the extraction of the target analytes from different kinds of water samples (river, lake, and swimming pool). The usage of a chitosan membrane in the extraction process presents many advantages, as it is a biodegradable and versatile support, offering a good alternative to commercial plastic materials commonly used in this methodology and these procedures.

Perceptions and attitudes regarding delayed antibiotic prescription for respiratory tract infections: a qualitative study.

BACKGROUND: Antibiotics are overprescribed for respiratory tract infections (RTIs). However, the decision to prescribe is often complex. Delayed antibiotic prescription (DAP), a strategy designed to promote more rational antibiotic use, is still not widely used. The aim of this study was to explore perceptions and attitudes in primary care professionals, regarding antibiotic use and different DAP strategies for uncomplicated RTIs. METHODS: We conducted a qualitative study, using an inductive thematic approach to generate themes, based on focus group discussions and semi-structured interviews with professionals, recruited from 6 primary care centres (Barcelona metropolitan area, Spain). RESULTS: 26 professionals (25 family physicians and one nurse) were included in four focus group discussions and three semi-structured interviews. Participants commented that RTIs were a main reason for consultation, motivated often by patient anxiety and fear of possible complications, and this was associated with the patients' poor health-related education. Acknowledging inappropriate antibiotic use in the health system, participants attributed this, mainly to defensive medicine strategies. DAP was used when in doubt about the aetiology, and considering factors related to patient-physician interactions. The main perceived advantage of DAP was that it could reduce the need for additional visits, while the main disadvantage was uncertainty regarding proper use by the patient. CONCLUSIONS: DAP was used by participants in cases of doubt, in specific situations, and for specific patient profiles. Weak points were detected in our primary care system and its users that affect the proper use of both antibiotics and DAP, namely, time pressure on professionals, poor patient health-related education, and the lack of a patient-physician relationship in some scenarios.

[Community-acquired bacteremia in adult patients attending the emergency service of a teaching hospital]. / Bacteriemias de origen comunitario en pacientes adultos que acuden al servicio de urgencias de un hospital universitario.

Bacteremia is an important cause of morbimortality. This study describes the episodes of community-acquired bacteremia in adult patients registered at our hospital. Between January 2005, and December 2009, 271 episodes were studied. The diagnostic yield of blood cultures was 13.5 %. A total of 52 % of patients were male and 48 % female. The mean age was 60. The most frequent comorbidities were: diabetes (21 %), neoplasia (18 %), cardiopathy (11 %), and HIV infection (8 %). The focus was- respiratory (21 %), urinary (15 %), cutaneous (9 %), and others (13 %). Gram-positive bacteria prevailed (51.4%). The most frequent microorganisms were Escherichia coli (25 %), Streptococcus pneumoniae (22.9 %), and Staphylococcus aureus (12.3 %). Bacteremia was polymicrobial in 7 % of the cases. Thirty three percent of E. coli isolates were resistant to ciprofloxacin and 6 % to ceftazidime. Fourteen percent of S. aureus strains were resistant to oxacillin whereas only 7 % of S. pneumoniae expressed high resistance to penicillin with MICs = 2 ug/ml, according to meningitis breakpoints.

[Intra-abdominal infections in adults caused by Streptococcus pneumoniae: report of 18 cases] / Infecciones intraabdominales en adultos causadas por Streptococcus pneumoniae: reporte de 18 casos.

Introduction: Streptococcus pneumoniae (Spn) is occasionally implicated as a cause of intra-abdominal infection (IIASpn) that can be 1) spontaneous bacterial peritonitis (SBP) in elderly patients with previous peritoneal disease, associated with cirrhosis, in most of the cases 2) associated or adjacent to an intra-abdominal organ or postsurgical. (IIAbq) 3) peritonitis in previously healthy young women (PHYW). Our objective is report 18 cases of IIASpn describing: clinical presentation, comorbidities, need for surgery, microbiological findings, sensitivity of Spn to antimicrobials, therapeutic behavior, and evolution. Methods: study of 18 adult patients with IIASpn. Clinical and microbiological characteristics and evolution of infections were analyzed. Results: IIASpn occurred in 9 PHYW, 6 men and 1 woman with SBP, and 2 men with appendicitis. The PHYW were operated on (4 pelviperitonitis, 3 salpingitis, 2 and tubo ovarian abscess) and had a favorable evolution. In the intraoperative samples, pure culture of Spn sensitive to penicillin was isolated. Three of four patients had positive blood culture. Five of seven patients with SBP died and in the peritoneal fluid developed Spn in pure culture. A large percentage of strains presented decreased sensitivity to penicillin. Four of five had a positive blood culture. Patients with appendicitis had favorable evolution. Conclusions: IIASpn in PHYW was the most frequent presentation, surgery played a significant role in treatment and the clinical response was excellent. The second presentation occurred in elderly patients with cirrhosis, most of whom died. Appendicitis was the third presentation in patients who evolved favorably.

Introducción: Streptococcus pneumoniae (Spn) ocasionalmente causa infección intraabdominal (IIASpn) que puede ser: 1) peritonitis bacteriana espontánea (PBE) en paciente añosos con enfermedad peritoneal previa, asociada con cirrosis, en la mayoría de los casos; 2) asociada o adyacente a un órgano intraabdominal o postquirúrgica (IIAbq); 3) peritonitis en mujeres jóvenes previamente sanas (MJPS). Nuestro objetivo es reportar 18 casos de IIASpn describiendo: presentación clínica, comorbilidades, necesidad de cirugía, microbiología y sensibilidad a los antimicrobianos, conducta terapéutica y evolución. Métodos: estudio de 18 pacientes adultos con IIASpn en un período de 23 años. Análisis de las características clínicas, microbiología y evolución de los pacientes. Resultados: las IIASpn ocurrieron en 9 MJPS, 6 varones y una mujer con PBE, y 2 varones con apendicitis. Las MJPS fueron intervenidas quirúrgicamente (4 pelviperitonitis, 3 salpingitis y 2 abscesos tubo ovárico) y evolucionaron favorablemente. En las muestras intraoperatorias se aisló Spn cultivo puro sensible a penicilina. Tres de cuatro pacientes tuvieron hemocultivo positivo. Cinco de siete pacientes con PBE fallecieron y en las muestras de líquido peritoneal desarrolló Spn cultivo puro. Gran porcentaje de cepas presentó sensibilidad disminuida a penicilina. Cuatro de cinco, tuvieron hemocultivo positivo. Los pacientes con apendicitis evolucionaron favorablemente. Conclusiones: La IIASpn en MJPS fue la presentación más frecuente, la cirugía jugó un rol significativo en el tratamiento y la respuesta clínica fue excelente. La segunda presentación ocurrió en pacientes añosos con cirrosis y en su mayoría, fallecieron. La apendicitis fue la tercera presentación en pacientes que evolucionaron favorablemente.

Capillary electrophoresis determination of nonsteroidal anti-inflammatory drugs in wastewater using hollow fiber liquid-phase microextraction.

The presence of pharmaceuticals in the environment due to growing worldwide consumption has become an important problem that requires analytical solutions. This paper describes a CE determination for several nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, ketoprofen, diclofenac, ketorolac, aceclofenac and salicylic acid) in environmental waters using hollow fiber membrane liquid-phase microextraction. The extraction was carried out using a polypropylene membrane supporting dihexyl ether and the electrophoretic separation was performed in acetate buffer (30 mM, pH 4) using ACN as the organic modifier. Detection limits between 0.25 and 0.86 ng/mL were obtained, respectively. The method could be applied to the direct determination of the seven anti-inflammatories in wastewaters, and five of them have been determined or detected in different urban wastewaters.

The Addition of Other Fecal Biomarkers Does Not Improve the Diagnostic Accuracy of Immunochemical Fecal Occult Blood Test Alone in a Colorrectal Cancer Screening Cohort.

Background: Screening with fecal occult blood test reduces colorectal cancer (CRC) incidence and mortality, and is currently implemented in most countries. However, around 40% of screening colonoscopies are normal. Thus, strategies to avoid these colonoscopies are highly necessary. Adding other fecal biomarkers, such as fecal calprotectin (FC), lactoferrin, and transferrin may be useful, but evidence is scarce. Aims: To evaluate the diagnostic accuracy of fecal occult blood immunochemical test (FIT), FC, and a one-step combo card test for the simultaneous semi-qualitative detection of human hemoglobin (hHb), transferrin (hTf), calprotectin (hCp) and lactoferrin (hLf) in a CRC screening program population. Methods: Single-center, prospective observational study, enrolling patients included in a CRC screening program, referred for a colonoscopy due to a positive FIT test. Participants collected a stool sample prior to bowel preparation, and FIT, FC and the combo semi-qualitative tests were performed on the sample. Sensitivity, specificity, positive and negative predictive values and area under receiver operator curve (AUC) for diagnosis of advanced neoplasia, advanced adenoma and CRC were estimated for each biomarker and their combinations. The primary endpoint of the study was to assess whether these biomarkers could improve the diagnostic accuracy of FIT alone. Results: 336 consecutive patients (64% males) were recruited. Advanced neoplasia was found in 129/336 (38.4%) patients, and of these, 22/336 (6.5%) were diagnosed of CRC. 153/336 (45.5%) colonoscopies were completely normal. The AUC for the diagnosis of advanced neoplasia were 0.725 (95%CI 0.665-0.784) for FIT, 0.477 (95%CI 0.413-0.541) for FC and 0.732 (95%CI 0.674-0.791) for the combination of both (FIT + FC) quantitative tests. The AUCs for the combo test were 0.70 (95%CI 0.641-0.760) for hHb, 0.625 (95%CI 0.562-0.698) for hTf, 0.532 (95%CI 0.469-0.595) for hCp, 0.531 (95%CI 0.466-0.595 ) for hLf and 0.681 (95%CI 0.620-0.741) for the combination of the four biomarkers. Conclusion: In average-risk population, FIT appears to be the best fecal marker for the diagnosis of CRC and advanced adenoma. None of the other biomarkers explored or their combinations provided a better diagnostic accuracy. Only hTF showed an acceptable diagnostic accuracy. FC and hLF were not useful in this setting.

Analytical quality by design in the development of a solvent-modified micellar electrokinetic chromatography method for the determination of sitagliptin and its related compounds.

A solvent-modified micellar electrokinetic chromatography method was developed following the Quality by Design approach for the simultaneous determination of sitagliptin (SIT), an oral antihyperglycemic drug, and its main impurities derived from the synthesis process. The separation system was identified in the scouting phase and was made by sodium dodecyl sulphate (SDS) micelles with the addition of n-butanol and methanol. The knowledge space was investigated through an asymmetric screening matrix, taking into consideration eight critical method parameters (CMPs) involving the composition of the background electrolyte in terms of buffer concentration and pH, the concentration of surfactants and organic modifiers, and voltage. The critical method attributes (CMAs) were identified as analysis time and the distance between the tail of the electroosmotic flow system peak and the front edge of impurity I1 (sitagliptin triazole hydrochloride). A Box-Behnken Design was used in response surface methodology for calculating the quadratic models relating the CMPs to the CMAs. From the models it was possible to compute the method operable design region (MODR) through Monte-Carlo simulations. The MODR was identified in the probability maps as the multidimensional zone where the risk of failure to achieve the desired values for the CMAs was lower than 10 %. The experimental conditions corresponding to the working point, with the MODR interval, were the following: background electrolyte, 14 (10-18) mM borate buffer pH 9.20, 100 mM SDS, 13.6 (11.1-16.0) %v/v n-butanol, 6.7 (4.5-8.8) %v/v methanol; voltage and temperature were set to 28 kV and 22 °C, respectively. The developed CE method was validated in accordance with International Council for Harmonisation guidelines and was applied to the analysis of SIT tablets. The routine analysis for the quality control of the pharmaceutical product could be conducted in about 11 min.

Chitosan biofilms: Insights for the selective electromembrane extraction of fluoroquinolones from biological samples.

A selective electromembrane extraction procedure for the extraction of Enrofloxacin, Marbofloxacin and Flumequine, usually employed as antibiotic in veterinarian use, is proposed by using a chitosan biofilm, composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336, as active biopolymeric support. The interaction mechanism occurring between the target drugs and the biopolymer has been deeply studied using the Quantum Theory of Atoms in Molecules. The obtained results show the interaction between the extracted fluoroquinolones and the biomembrane is stabilized by two hydrogen bonds formed between both the carboxyl and keto groups of the drugs with both the amine and hydroxyl groups of glucosamine in the biopolymer. The energetic results agree with the high extraction efficiency obtained for Marbofloxacin, Enrofloxacin and Flumequine in terms of enrichment factors (83, 82 and 58, respectively) in presence of other fluoroquinolones. Under optimum conditions, the proposed electromembrane extraction method exhibits wide linear ranges of 4.2-200 µg L-1, 5.6-200 µg L-1 and 5.1-200 µg L-1, respectively; low limits of detection close to 1.3 µg L-1 and appropriate repeatability (relative standard deviation values 4-7%).