Análisis de la carga laboral en tiempo médico en función del grado de complejidad de las muestras y propuesta de algoritmo para la distribución equitativa del trabajo asistencial en un servicio de anatomía patológica / Analysis of the workload in medical time according to the degree of complexity of the samples and proposal of an algorithm for the equitable distribution of the workload in an anatomic pathology department

Introducción: En un servicio de anatomía patológica se analiza la carga laboral en tiempo médico en función de la complejidad de las muestras recibidas, y se valora su distribución entre los patólogos, presentado un nuevo algoritmo informático que favorece una distribución equitativa. Métodos: Siguiendo las directrices para la «Estimación de la carga de trabajo en citopatología e histopatología (tiempo médico) atendiendo al catálogo de muestras y procedimientos de la SEAP-IAP (2.ª edición)» se determinan las unidades de carga laboral (UCL) por patólogo y UCL global del servicio, la carga media laboral que soporta el servicio (factor MU), el tiempo de dedicación de cada patólogo a la actividad asistencial y el número de patólogos óptimo según la carga laboral del servicio. Resultados: Determinamos 12.197 UCL totales anuales para el patólogo jefe de servicio, así como 14.702 y 13.842 para los patólogos adjuntos, con una UCL global del servicio de 40.742. El factor MU calculado es 4,97. El jefe ha dedicado el 72,25% de su jornada a la asistencia y los adjuntos el 87,09 y 82,01%. El número de patólogos óptimo para el servicio es de 3,55. Conclusiones: Todos los resultados obtenidos demuestran la sobrecarga laboral médica, y la distribución de las UCL entre los patólogos no resulta equitativa. Se propone un algoritmo informático capaz de distribuir la carga laboral de manera equitativa, asociado al sistema de información del laboratorio, y que tenga en cuenta el tipo de muestra, su complejidad y la dedicación asistencial de cada patólogo.(AU)

Introduction: In a pathological anatomy service, the workload in medical time is analyzed based on the complexity of the samples received and its distribution among pathologists is assessed, presenting a new computer algorithm that favors an equitable distribution. Methods: Following the second edition of the Spanish guidelines for the estimation of workload in cytopathology and histopathology (medical time) according to the Spanish Pathology Society-International Academy of Pathology (SEAP-IAP) catalog of samples and procedures, we determined the workload units (UCL) per pathologist and the overall UCL of the service, the average workload of the service (MU factor), the time dedicated by each pathologist to healthcare activity and the optimal number of pathologists according to the workload of the service. Results: We determined 12 197 total annual UCL for the chief pathologist, as well as 14 702 and 13 842 UCL for associate pathologists, with an overall of 40 742 UCL for the whole service. The calculated MU factor is 4.97. The chief pathologist devoted 72.25% of his working day to healthcare activity while associate pathologists dedicated 87.09% and 82.01% of their working hours. The optimal number of pathologists for the service is found to be 3.55. Conclusions: The results demonstrate medical work overload and a non-equitable distribution of UCLs among pathologists. We propose a computer algorithm capable of distributing the workload in an equitable manner. It would be associated with the laboratory information system and take into account the type of specimen, its complexity and the dedication of each pathologist to healthcare activity.(AU)

Obstetric and neonatal outcomes, antiseizure medication profile, and seizure types in pregnant women in a vulnerability state from Brazil.

This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy (PWWE). Data collected from the medical records of 224 PWWE aged < 40 years with controlled or refractory seizures and 492 pregnant women without epilepsy (PWNE) control group from high-risk maternity hospitals in Alagoas between 2008 and 2021 were included in this study. The obstetric and neonatal outcomes observed in PWWE were pregnancy-related hypertension (PrH) (18.4%), oligohydramnios (10.3%), stillbirth (6.4%), vaginal bleeding (6%), preeclampsia (4.7%), and polyhydramnios (3%). There was a greater likelihood of PrH in PWWE with generalized tonic-clonic seizures (GTCS) and that of maternal intensive care unit (ICU) admissions in those with GTCS and status epilepticus, and phenytoin and lamotrigine use. PWWE with GTCS had a higher risk of stillbirth and premature delivery. PWWE with status epilepticus were treated with lamotrigine. Phenobarbital (PB) with diazepam were commonly used in GTCS and status epilepticus. Total 14% patients did not use ASM, while 50.2% used monotherapy and 35.8% used polytherapy. Total 60.9% of patients used PB and 25.2% used carbamazepine. This study described the association between the adverse obstetric and neonatal outcomes and severe seizure types in PWWE.

Social influence, performance expectancy, and price value as determinants of telemedicine services acceptance in Chile.

Medicine is a discipline based on and nurtured by scientific research and technological development. The use of health services supported by information technology is increasing worldwide, and Latin America is no exception. Factors such as needing more specialists in peripheral cities, large geographic areas, and socio-cultural aspects limit the possibility of receiving timely and quality medical care services. Information Technology (IT) for health purposes, such as e-health, is a cost-effective solution for equitable access to quality healthcare services and optimization of the rising associated costs. As an e-health service, telemedicine facilitates and mediates distance communication between the patient and medical staff. Even though Latin America is at the beginning of the development of telemedicine, it would have a relevant impact, given the geographic and socioeconomic conditions of the population in this part of the world. Drawing on the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) theory, we developed a theoretical model to identify the latent factors influencing the public acceptance of telemedicine and examined their interrelationships. A survey questionnaire was designed and administered to 391 residents in Antofagasta, a mine region of Chile. After that, structural equation modeling was employed to analyze the survey data. The results reveal that the UTAUT2 factors' performance expectancy, social influence, and price value significantly impact the intention to use (R2 = 0.693). Additionally, the model presented a good fit. This study enriches the existing theoretical research on the acceptance of telemedicine services and offers insights into understanding and managing technology in the Chilean health sector.

Bilateral Spigelian Hernias Robotic Repair: A Novel Approach to a Rare Surgical Entity.

Spigelian hernias are an uncommon protrusion defect noted between the rectus abdominis and the transversus abdominis muscles, at the semilunar line, with a low incidence of approximately 0.12% to 2% of all ventral hernias. Furthermore, the incidence of bilateral cases is noted to be even lower in the general population. They are associated with bowel incarceration and strangulation; hence surgical repair is indicated. Therapeutic alternatives for Spigelian hernias include open repair, however laparoscopic repair stands as the standard of care in these cases. Feasible and successful robotic repair has been reported, with associated advantages in terms of visualization and surgical instrument dexterity. We present the first ever reported cases of bilateral Spigelian hernias repaired using robotic approach. Two female Puerto Rican patients referred to our institution complaining of abdominal pain, where imaging studies found bilateral Spigelian hernias. In both cases, a transabdominal preperitoneal repair was performed using the Da Vinci Surgical System. Both patients were discharged home tolerating oral intake with adequate wound healing. On follow up visits, patients denied abdominal discomfort and had adequate wound healing. Robotic surgery for Spigelian hernias poses an advantage over laparoscopic repair as improved visualization, mobility, and precision in movements allow for more gentle tissue manipulation. Furthermore, this is the first evidence of safe and effective repair in the uncommon entity of bilateral cases, providing a newer alternative in the setting of such presentation.

Perceived Ageism is Associated With Recurrent Falling Among Older Colombian Adults.

Literature on the association between ageism and falling among older adults is limited. Using data from the nationwide cross-sectional SABE (Salud, Bienestar y Envejecimiento) Colombia Survey in 2015 with 18,875 participants aged ≥60 years living in the communities, the study aims to evaluate the association between perceived ageism within the family, neighborhood, health services, and public services, and recurrent falling. Participants had a mean age of 69.2 ± 7.1; 56.1% were female. Recurrent falling prevalence was 15%, and experiencing any ageism was 10%. Multivariable logistic regression analyses showed higher odds of recurrent falling for any ageism (OR = 1.81, 95% CI 1.61-2.02, p < .0001). High depressive symptoms mediated 10.1% of the association between any ageism and recurrent falling, followed by low instrumental activities of daily living (9.7%) and multimorbidity (9.3%). Current findings open new areas of gerontological research by expanding the risk factors for falling among older adults to include ageism perceptions.

Sampling of microplastics at a materials recovery facility.

Detecting, separating, and characterizing airborne microplastics from other airborne particulates is currently challenging due to the various instrumental constraints and related sample preparation hurdles that must be overcome. The ability to measure these real-world environments is needed to better assess the risks associated with microplastics. To that end, the current study focused on developing a methodology for sampling and characterizing airborne microplastics. Particulate sampling was carried out at a municipal materials recovery facility near a conveyer belt containing sorted plastic materials to collect airborne environmental particles on filters. Nucleopore filters were mounted on Teflon support rings, coated with 100 nm aluminum to reduce the background signal for micro-Raman spectroscopy, and marked with a fiducial pattern using a laser engraver. The fiducial pattern was crucial in identifying samples, relocating particles, and efficiently enabling orthogonal measurements on the same samples. Optimum sampling conditions of 2 h at 25 L/min were determined using light microscopy to evaluate the particle loadings. The filters were then cut into slices which were attached to sections of thin beryllium-copper sheeting for easy transfer of the filter between microscopy platforms. Scanning electron microscopy was used to identify carbon-rich particles. Light microscopy was used to identify colored particles which were also carbon-rich which were then analyzed using micro-Raman spectroscopy to identify specific polymers.

Integrated photon pair source based on a silicon nitride micro-ring resonator for quantum memories.

We report the design of an integrated photon pair source based on spontaneous four-wave mixing (SFWM), implemented in an integrated micro-ring resonator in the silicon nitride platform (Si3N4). The signal photon is generated with emission at 606 nm and bandwidth of 3.98 MHz, matching the spectral properties of praseodymium ions (Pr), while the idler photon is generated at 1430.5 nm matching the wavelength of a CWDM channel in the E-band. This novel, to the best of our knowledge, device is designed to interact with a quantum memory based on a Y2SiO5 crystal doped with Pr3+ ions, in which we used cavity-enhanced SFWM along with dispersion engineering to reach the required wavelength and the few megahertz signal photon spectral bandwidth.

Higher order aberrations according to spherical, and astigmatic refractive errors in children.

CLINICAL RELEVANCE: The results of this study present novel insights into the impact of spherical and astigmatic refractive errors on overall, corneal and internal aberrations and may provide a clear understanding of the emmetropisation process and the development of visual function. BACKGROUND: This study aimed to assess the association between overall, corneal and internal higher-order aberrations and the spherical and astigmatic components (magnitude and angle) of refractive error in a large sample of children. METHODS: A total of 311 children aged 7 - 8 years old were classified based on spherical equivalent refraction (myopic, emmetropic and hyperopic); magnitude of astigmatism (none, low and moderate); and angle of astigmatism (with-the-rule, against-the-rule and oblique). Refractive error and overall, corneal and internal higher-order aberrations were measured using the OPD-Scan III workstation. RESULTS: Regarding spherical equivalent refraction, myopic eyes had greater root mean square (RMS) overall higher-order values, total spherical, tetrafoil and secondary astigmatism aberrations, and internal higher-order, total spherical and tetrafoil aberrations in comparison to emmetropic eyes. The magnitude of astigmatism was positively associated with all overall RMS aberrations and with internal higher order, coma, total coma, total spherical and tetrafoil aberrations. Eyes with with-the-rule astigmatism showed higher RMS values of coma and total coma compared to eyes with against-the-rule and oblique astigmatism. CONCLUSIONS: Higher-order aberrations are dependent on the spherical as well as astigmatic components of refractive error. These findings enhance the current understanding of the emmetropisation process and visual function development.

Improved hydrolysis of sewage sludge by air-assisted non-thermal plasma for enhanced biomethane recovery.

Conventional pretreatment technologies have been assessed to resolve the slow hydrolysis of sewage sludge, but high operating costs have prevented their wide use. This study investigated non-thermal plasma (NTP) technologies as an alternative to promote anaerobic digestion (AD). Various contact time (CT) and temperature (T) conditions were used to assess how NTP pretreatment improves the methane conversion of organics in sewage sludge. A multi-response surface model (RSM) using a central composite design (CCD) identified the optimal CT (4.6 h) and T (45 °C). This statistical optimization of NTP pretreatment led to an enhanced biochemical methane potential of 297 ± 46 mL CH4 g-1 COD by reducing operating cost as power consumption as low as 0.08 USD L-1. The result was comparable to those of other advanced oxidation processes (0.14 - 0.60 USD L-1) demonstrating that accelerated hydrolysis of sewage sludge using NTP pretreatment show potential for improving renewable energy recovery from sewage sludge.

Evaluation of electrode separators and the external resistance in electrochemically assisted constructed wetlands.

A proton exchange membrane increases the electrical performance of a microbial fuel cell (MFC). New inexpensive materials should be sought, especially in a constructed wetland microbial fuel cell (CW-MFC). Here, in a laboratory-scale system of five CW-MFCs, wet clay, wet earth or mud, and non-woven cloth were used as inexpensive separators with long-term stability. The five CW-MFCs were planted with Typha latifolia, fed with synthetic wastewater, and packed with natural porous material. Graphite felt was used as electrodes and the experimental system had a hydraulic residence time of 3 days, operating under shade and natural conditions of temperature and light. Electrodes were connected to current collectors (copper wire) and to an external resistance, with a change every 20 days, starting in open-circuit and following with 20000, 18000, 15000, 10000, 5600, 1000, 560, and 10 Ω. These laboratory-scale CW-MFCs reduced concentrations of nitrates, ammonium ion, and sulfates without inhibiting electricity production. Microbiological analyses indicated that anaerobic, facultative, aerobic, and denitrifying bacteria may have caused these reductions. The reactor with the live plant and with the wet earth or mud separator achieved the highest production of electricity (22.6 mW/m2), and may be worth further attention.

ß-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer's disease.

Introduction: The study of the pathophysiology study of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. Methods: The humanized APPNL-G-F knock-in mouse line was crossed to the PS19 MAPTP301S, over-expression mouse line to create the dual APPNL-G-F/PS19 MAPTP301S line. The resulting pathologies were characterized by immunochemical methods and PCR. Results: We now report on a double transgenic APPNL-G-F/PS19 MAPTP301S mouse that at 6 months of age exhibits robust A plaque accumulation, intense MAPT pathology, strong inflammation and extensive neurodegeneration. The presence of A pathology potentiated the other major pathologies, including MAPT pathology, inflammation and neurodegeneration. MAPT pathology neither changed levels of amyloid precursor protein nor potentiated A accumulation. Interestingly, study of immunofluorescence in cleared brains indicates that microglial inflammation was generally stronger in the hippocampus, dentate gyrus and entorhinal cortex, which are regions with predominant MAPT pathology. The APPNL-G-F/MAPTP301S mouse model also showed strong accumulation of N6-methyladenosine (m6A), which was recently shown to be elevated in the AD brain. m6A primarily accumulated in neuronal soma, but also co-localized with a subset of astrocytes and microglia. The accumulation of m6A corresponded with increases in METTL3 and decreases in ALKBH5, which are enzymes that add or remove m6A from mRNA, respectively. Discussion: Our understanding of the pathophysiology of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. The APPNL-G-F/MAPTP301S mouse recapitulates many features of AD pathology beginning at 6 months of aging, and thus represents a useful new mouse model for the field.

Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a document by the European Renal Best Practice board of the European Renal Association.

Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis stimulating agents (ESAs) and blood transfusions has been the mainstay of treatment of anaemia in CKD for more than three decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate-to-severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalisation, cardiovascular events, and CKD progression in patients with CKD, and the risk increases with anaemia severity. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body's response to hypoxia and have emerged as an alternative to ESAs for the treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in over 30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumor growth requires to be fully elucidated. This document presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties, and discusses their place in the treatment of anaemia in CKD according to the available evidence.

Effect of the Photoexcitation Wavelength and Polarization on the Generated Heat by a Nd-Doped Microspinner at the Microscale.

Thermal control at small scales is critical for studying temperature-dependent biological systems and microfluidic processes. Concerning this, optical trapping provides a contactless method to remotely study microsized heating sources. This work introduces a birefringent luminescent microparticle of NaLuF4:Nd3+ as a local heater in a liquid system. When optically trapped with a circularly polarized laser beam, the microparticle rotates and heating is induced through multiphonon relaxation of the Nd3+ ions. The temperature increment in the surrounding medium is investigated, reaching a maximum heating of ≈5 °C within a 30 µm radius around the static particle under 51 mW laser excitation at 790 nm. Surprisingly, this study reveals that the particle's rotation minimally affects the temperature distribution, contrary to the intuitive expectation of liquid stirring. The influence of the microparticle rotation on the reduction of heating transfer is analyzed. Numerical simulations confirm that the thermal distribution remains consistent regardless of spinning. Instead, the orientation-dependence of the luminescence process emerges as a key factor responsible for the reduction in heating. The anisotropy in particle absorption and the lag between the orientation of the particle and the laser polarization angle contribute to this effect. Therefore, caution must be exercised when employing spinning polarization-dependent luminescent particles for microscale thermal analysis using rotation dynamics.

Inter-laboratory comparison of routine autoantibody detection methods for autoimmune neuropathies and myasthenia gravis.

Serological tests are important to detect autoantibodies (autoAbs) in patients with autoimmune neuropathies (AN) and myasthenia gravis (MG) as they are biomarkers for diagnosis, stratification, treatment selection, and monitoring. However, tests to detect autoAbs frequently lack proper standardization and results differ across diagnostic laboratories. We compared results for tests routinely performed in Spanish diagnostic laboratories to detect AN and MG autoAbs. In the Spanish Society of Immunology Autoimmunity Group national workshop, serum samples from 13 patients with AN or MG were tested for anti-ganglioside, anti-myelin-associated glycoprotein (MAG), anti-nicotinic acetylcholine receptor (AChR), and anti-muscle-specific kinase (MuSK) autoAbs using reference methods and were distributed for analysis to 27 participating laboratories using their routine methods. Overserved were inter-laboratory variability and worryingly low sensitivity, especially for anti-ganglioside immunoglobulin G and anti-MAG autoAb detection. This pilot study reflects autoAbs detection state of the art in AN and MG testing in leading diagnostic laboratories in Spain, highlighting the need for standardization prior to clinical use.

Development of an online optical prototype for the simultaneous analysis of defects or gels in industrially synthesized polypropylene films. Part 1: Comparison with ASTM D 3351-93 methods.

Polypropylene (PP) films are crucial in various industrial applications, from packaging to medical products. However, a common challenge in PP manufacturing is the presence of gel-like defects. These gels are minor defects on the surface of the films that significantly affect the physicochemical, mechanical, and organoleptic properties of the films, compromising the quality of the final product. This first research focuses on developing and validating an in-line optical method to replace the international method ASTM D 3351-93. The main objective was to create a methodology that has the same scope and analytical performance as those reported by ASTM D 3351-93 in such a way that it can compete with it in terms of precision and accuracy, thus allowing end users to this ASTM, such as PP producers, PP marketers, PP film producers, among others internationally, can use this new methodology with necessary analytical support. This analytical methodology integrates the PP extrusion zones, the film processing stages, and the optical zone for reading and processing analytical data. Additionally, it has the advantage of working with a sample size that is even more representative of the population and has less human error since only one operator is required to carry out the test; this method also has much shorter response times. The developed prototype had 14 online stages that allowed representative quantities of samples to be taken and processed thermally and mechanically for ideal optical measurement. For the online method, a 6-point calibration curve is carried out at concentrations of 40, 10, 5, 2, 1 and 0 ppm for the gel or defect sizes of 200, 400, 500, 600, 700, 800 and 900 µm, showing excellent linearity where the correlation coefficient varied between 0.997 and 0.999, the limits of detection (LOD) varied between 0.85 and 2.61 and the limits of quantification (LOQ) ranged between 2.82 and 8.71. The statistical analyzes by ANOVA of the comparison between the ASTM D 3351-93 method and the proposed simultaneous method indicate that the p value of the evaluation of the means was 0.946, which suggests that the means are not statistically different. To complement, the Tukey test was carried out at 95 %, indicating that the methods have statistical equivalence.•Process optimization•Determination of defects or imperfections in PP films.

Coronary Artery Embolism and Myocardial Infarction, case report.

Coronary embolism (CE) is a rare cause of non-atherosclerotic acute coronary syndrome (ACS). The clinical presentation is similar to ACS, and the diagnosis is supported by Shibata criteria. Atrial fibrillation is the main reported etiology in CE cases. Management includes percutaneous intervention with thromboaspiration and anticoagulation. The following case is a description of a patient with acute chest pain and recently diagnosed atrial fibrillation (AF) with a rapid ventricular response, is described. A thrombotic lesion in the distal right coronary artery (RCA) of embolic origin, was documented. Successful mechanical thromboaspiration was performed; intravascular ultrasound (IVUS) showed no thrombus, dissection, or atherosclerotic plaque. CE is an underdiagnosed cause of ACS; diagnosis relies on Shibata criteria, and patients experience worse outcomes in follow-up.

Incidence, treatment, and factors associated with survival of out-of-hospital cardiac arrest attended by Spanish emergency services: report from the Out-of-Hospital Spanish Cardiac Arrest Registry for 2022. / Incidencia, tratamiento y factores asociados con la supervivencia de la parada cardiaca extrahospitalaria atendida por los servicios de emergencias en España: informe 2022 del registro OHSCAR.

SUMMARY: Out-of-hospital cardiac arrest is a serious public health problem worldwide. The annual incidence is estimated at around 400 000 cases in Europe and the United States, and survival rates scarcely reach 10%. However, there is considerable variation between countries and even between regions that share a similar health care system within a single country. Information recorded by the Out-of-Hospital Spanish Cardiac Arrest Registry (OHSCAR) provides information on care provided by emergency ambulance services, final health outcomes after cardiac arrest cases (including variations), the possibility of organ donation, and the impact of the COVID-19 pandemic. This paper presents the OHSCAR report for Spanish emergency services for the year 2022.

RESUMEN: La parada cardiorrespiratoria extrahospitalaria (PCREH) es un grave problema de salud pública mundial, con una incidencia anual estimada entorno a entorno a los 350.000 y 400.000 casos de PCERH en Europa y Estados Unidos, respectivamente. La supervivencia final se sitúa en porcentajes que apenas alcanzan el 10%, aunque existe una importante variabilidad entre países e incluso entre regiones del mismo país con modelos de atención similares. En España, el Registro Español de Parada Cardiaca Extrahospitalaria (acrónimo OHSCAR) ha ofrecido información sobre la asistencia a la PCRE prestada por los servicios de emergencias (SEM) y sus resultados finales en salud, así como sobre variabilidad, posibilidades de programas de donación o impacto de la pandemia COVID-19. A continuación se presenta el informe OHSCAR correspondiente a la asistencia a la PCRE por los SEM españoles durante el año 2022.

Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: A prospective cohort study.

OBJECTIVES: This study aimed to determine the association of E. coli microbiological factors with 30-day mortality in BSI patients presenting with a dysregulated response to infection (i.e., sepsis or septic shock). METHODS: Whole genome sequencing was performed on 224 E. coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02-1.07), Charlson index ≥3 (1.78; 0.95-3.32), urinary BSI source (0.30; 0.16-0.57) and active empirical treatment (0.36; 0.11-1.14) with an AUROC of 0.73 (95% CI, 0.67-0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94-14.04), eilA gene (2.62; 1.14-6.02) and astA gene (2.39; 0.87-6.59) as associated with mortality, with an AUROC of 0.76 (0.69-0.82). CONCLUSIONS: Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and would deserve being studied as potential therapeutic or preventive targets.

Xylazine does not enhance fentanyl reinforcement in rats: A behavioral economic analysis.

The adulteration of illicit fentanyl with the alpha-2 agonist xylazine has been designated an emerging public health threat. The clinical rationale for combining fentanyl with xylazine is currently unclear, and the inability to study fentanyl/xylazine interactions in humans warrants the need for preclinical research. We studied fentanyl and xylazine pharmacodynamic and pharmacokinetic interactions in male and female rats using drug self-administration behavioral economic methods. Fentanyl, but not xylazine, functioned as a reinforcer under both fixed-ratio and progressive-ratio drug self-administration procedures. Xylazine combined with fentanyl at three fixed dose-proportion mixtures did not significantly alter fentanyl reinforcement as measured using behavioral economic analyses. Xylazine produced a proportion-dependent decrease in the behavioral economic Q0 endpoint compared to fentanyl alone. However, xylazine did not significantly alter fentanyl self-administration at FR1. Fentanyl and xylazine co-administration did not result in changes to pharmacokinetic endpoints. The present results demonstrate that xylazine does not enhance the addictive effects of fentanyl or alter fentanyl plasma concentrations. The premise for why illicitly manufacture fentanyl has been adulterated with xylazine remains to be determined.