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Many medical imaging modalities have benefited from recent advances in Machine Learning (ML), specifically in deep learning, such as neural networks. Computers can be trained to investigate and enhance medical imaging methods without using valuable human resources. In recent years, Fluorescence Lifetime Imaging (FLIm) has received increasing attention from the ML community. FLIm goes beyond conventional spectral imaging, providing additional lifetime information, and could lead to optical histopathology supporting real-time diagnostics. However, most current studies do not use the full potential of machine/deep learning models. As a developing image modality, FLIm data are not easily obtainable, which, coupled with an absence of standardisation, is pushing back the research to develop models which could advance automated diagnosis and help promote FLIm. In this paper, we describe recent developments that improve FLIm image quality, specifically time-domain systems, and we summarise sensing, signal-to-noise analysis and the advances in registration and low-level tracking. We review the two main applications of ML for FLIm: lifetime estimation and image analysis through classification and segmentation. We suggest a course of action to improve the quality of ML studies applied to FLIm. Our final goal is to promote FLIm and attract more ML practitioners to explore the potential of lifetime imaging.
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Procesamiento de Imagen Asistido por Computador , Aprendizaje Automático , Humanos , Microscopía Fluorescente/métodos , Imagen ÓpticaRESUMEN
Label-free autofluorescence lifetime is a unique feature of the inherent fluorescence signals emitted by natural fluorophores in biological samples. Fluorescence lifetime imaging microscopy (FLIM) can capture these signals enabling comprehensive analyses of biological samples. Despite the fundamental importance and wide application of FLIM in biomedical and clinical sciences, existing methods for analysing FLIM images often struggle to provide rapid and precise interpretations without reliable references, such as histology images, which are usually unavailable alongside FLIM images. To address this issue, we propose a deep learning (DL)-based approach for generating virtual Hematoxylin and Eosin (H&E) staining. By combining an advanced DL model with a contemporary image quality metric, we can generate clinical-grade virtual H&E-stained images from label-free FLIM images acquired on unstained tissue samples. Our experiments also show that the inclusion of lifetime information, an extra dimension beyond intensity, results in more accurate reconstructions of virtual staining when compared to using intensity-only images. This advancement allows for the instant and accurate interpretation of FLIM images at the cellular level without the complexities associated with co-registering FLIM and histology images. Consequently, we are able to identify distinct lifetime signatures of seven different cell types commonly found in the tumour microenvironment, opening up new opportunities towards biomarker-free tissue histology using FLIM across multiple cancer types.
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The electrochemical degradation of 2-chlorophenol (2-CP) on boron-doped diamond (BDD) anodes was carried out using two electrolytes, NaCl and Na2SO4. Both electrolytes supported complete mineralization of 2-CP, but faster rates of degradation were observed in NaCl. After 4 h of oxidation, the total organic carbon (TOC) balance neared 100% with Na2SO4 for identifiable compounds, whereas 4 mM of TOC remained unidentified with NaCl. Since chlorophenols are known to be precursors of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), a rigorous assessment of intermediate products was carried out. When near complete mineralization was achieved, the use of NaCl resulted in the concentration of total PCDD/Fs increasing 2.68 × 10(4) times compared to the untreated sample, and to toxicity values several times higher than the maximum level established by U.S. Environmental Protection Agency for water ingestion. When Na2SO4 was used, the increase in total PCDD/Fs concentration was 134 times lower than with NaCl and there was no significant 2,3,7,8-PCDD/Fs formation. Thus, we emphasize the importance of electrolyte selection in electro-oxidation processes, especially when PCDD/Fs precursors are initially present or may be formed in the treated water samples.
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Benzofuranos/química , Clorofenoles/química , Electrólitos/química , Dibenzodioxinas Policloradas/análogos & derivados , Electroquímica , Cinética , Oxidación-Reducción , Dibenzodioxinas Policloradas/química , Cloruro de Sodio/química , Soluciones , Sulfatos/químicaRESUMEN
Autofluorescence lifetime images reveal unique characteristics of endogenous fluorescence in biological samples. Comprehensive understanding and clinical diagnosis rely on co-registration with the gold standard, histology images, which is extremely challenging due to the difference of both images. Here, we show an unsupervised image-to-image translation network that significantly improves the success of the co-registration using a conventional optimisation-based regression network, applicable to autofluorescence lifetime images at different emission wavelengths. A preliminary blind comparison by experienced researchers shows the superiority of our method on co-registration. The results also indicate that the approach is applicable to various image formats, like fluorescence in-tensity images. With the registration, stitching outcomes illustrate the distinct differences of the spectral lifetime across an unstained tissue, enabling macro-level rapid visual identification of lung cancer and cellular-level characterisation of cell variants and common types. The approach could be effortlessly extended to lifetime images beyond this range and other staining technologies.
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Aprendizaje Profundo , Coloración y EtiquetadoRESUMEN
Multi-scale architectures at a granular level are characterised by separating input features into groups and applying multi-scale feature extractions to the split input features, and thus the correlations among the input features as global information are no longer retained. Moreover, they usually require more input features due to the separation, and therefore, more complexity is introduced. To retain the global information while utilising the advantages of feature-level hierarchical multi-scale architectures, we propose a multi-scale aggregated-dilation architecture (MSAD) to perform hierarchical fusion of features at a layer level, with the integration of dilated convolutions to overcome these issues. To evaluate the model, we integrate it into ResNet, and apply it to a unique dataset, containing over 60,000 fluorescence lifetime endomicroscopic images (FLIM) collected on ex-vivo lung normal/cancerous tissues from 14 patients, by a custom fibre-based FLIM system. To evaluate the performance of our proposal, we use accuracy, precision, recall, and AUC. We first compare our MSAD model with eight networks achieving a superiority over 6%. To illustrate the advantages and disadvantages of multi-scale architectures at layer and feature-level, we thoroughly compare our MSAD model with the state-of-the-art feature-level multiscale network, namely Res2Net, in terms of parameters, scales, and effective convolutions.
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Neoplasias Pulmonares , Redes Neurales de la Computación , Dilatación , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , TóraxRESUMEN
Parkinson's disease is a disorder that affects the neurons in the human brain. The various symptoms include slowness of motor functions (bradykinesia), motor instability, speech impairment and in some cases, psychiatric effects such as hallucinations. Most of these, however, are also common side effects of natural aging. This makes an accurate diagnosis of Parkinson's disease a challenging task. Some breakthroughs have been made in recent years with the help of deep learning. This work aims at considering figure drawing data as a time series of coordinates, angles and pressure readings to train recurrent neural network models. In addition, the work compares two recurrent network models, Long Short-Term Memory and Echo State Networks, to explore the advantages and disadvantages of both architectures.
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Enfermedad de Parkinson , Encéfalo , Humanos , Hipocinesia , Redes Neurales de la Computación , Trastornos del HablaRESUMEN
Due to the continued evolution of the SARS-CoV-2 pandemic, researchers worldwide are working to mitigate, suppress its spread, and better understand it by deploying digital signal processing (DSP) and machine learning approaches. This study presents an alignment-free approach to classify the SARS-CoV-2 using complementary DNA, which is DNA synthesized from the single-stranded RNA virus. Herein, a total of 1582 samples, with different lengths of genome sequences from different regions, were collected from various data sources and divided into a SARS-CoV-2 and a non-SARS-CoV-2 group. We extracted eight biomarkers based on three-base periodicity, using DSP techniques, and ranked those based on a filter-based feature selection. The ranked biomarkers were fed into k-nearest neighbor, support vector machines, decision trees, and random forest classifiers for the classification of SARS-CoV-2 from other coronaviruses. The training dataset was used to test the performance of the classifiers based on accuracy and F-measure via 10-fold cross-validation. Kappa-scores were estimated to check the influence of unbalanced data. Further, 10 × 10 cross-validation paired t-test was utilized to test the best model with unseen data. Random forest was elected as the best model, differentiating the SARS-CoV-2 coronavirus from other coronaviruses and a control a group with an accuracy of 97.4 %, sensitivity of 96.2 %, and specificity of 98.2 %, when tested with unseen samples. Moreover, the proposed algorithm was computationally efficient, taking only 0.31 s to compute the genome biomarkers, outperforming previous studies.
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COVID-19 , SARS-CoV-2 , Algoritmos , Humanos , Aprendizaje Automático , PandemiasRESUMEN
Fluorescence lifetime is effective in discriminating cancerous tissue from normal tissue, but conventional discrimination methods are primarily based on statistical approaches in collaboration with prior knowledge. This paper investigates the application of deep convolutional neural networks (CNNs) for automatic differentiation of ex-vivo human lung cancer via fluorescence lifetime imaging. Around 70,000 fluorescence images from ex-vivo lung tissue of 14 patients were collected by a custom fibre-based fluorescence lifetime imaging endomicroscope. Five state-of-the-art CNN models, namely ResNet, ResNeXt, Inception, Xception, and DenseNet, were trained and tested to derive quantitative results using accuracy, precision, recall, and the area under receiver operating characteristic curve (AUC) as the metrics. The CNNs were firstly evaluated on lifetime images. Since fluorescence lifetime is independent of intensity, further experiments were conducted by stacking intensity and lifetime images together as the input to the CNNs. As the original CNNs were implemented for RGB images, two strategies were applied. One was retaining the CNNs by putting intensity and lifetime images in two different channels and leaving the remaining channel blank. The other was adapting the CNNs for two-channel input. Quantitative results demonstrate that the selected CNNs are considerably superior to conventional machine learning algorithms. Combining intensity and lifetime images introduces noticeable performance gain compared with using lifetime images alone. In addition, the CNNs with intensity-lifetime RGB image is comparable to the modified two-channel CNNs with intensity-lifetime two-channel input for accuracy and AUC, but significantly better for precision and recall.
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Aprendizaje Profundo , Neoplasias Pulmonares , Algoritmos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. AIM: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. METHODS: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. RESULTS: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. DISCUSSION: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.
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Antibacterianos/administración & dosificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Ertapenem/administración & dosificación , Unidades de Cuidados Intensivos , Adulto , Anciano , Colombia , Enfermedad Crítica , Infecciones por Enterobacteriaceae/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Pseudomonas/efectos de los fármacos , Factores de Riesgo , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
Drug targeting may contribute to overcoming resistance to chemotherapy and to reducing side effects. Here, by conjugating a nitrogenated base (NB) to the side chain of a bile acid (BA) moiety, we have synthesized and evaluated six novel compounds, designated BANB-1 to -6, with potential cytostatic activity and vectoriality toward enterohepatic tumors. These compounds were purified by liquid chromatography and their purity was checked by TLC and HPLC before being chemically characterized using IR, (1)H/(13)C NMR and FAB-MS. Using several cell lines - HepG2 (human hepatoblastoma), LS 174T and Caco-2 (human colon adenocarcinoma), Hepa 1-6 (mouse hepatoma), McA-RH7777 (rat hepatoma), CCRF S-180 II (mouse sarcoma) and CHO (Chinese hamster ovary) - their effect on cell viability was measured with the formazan test after drug exposure for 6h (cytotoxic effect) or 72h (cytostatic effect). A weak cytostatic effect of BANB-1, BANB-2 and BANB-3 was detected even in CHO cells stably transfected with rat bile acid transporters (Ntcp and Oatp1/1a1). In contrast, BANB-4, BANB-5 and BANB-6, similarly to cisplatin, showed strong cytostatic effects, together with mild non-specific toxicity. BANB-6 was effective even against Hepa 1-6/R cells, which were partly resistant to cisplatin. Treatment with BANB-6, but not cisplatin, was able to prolong the life span of Nude mice bearing tumors formed by Hepa 1-6/R cells orthotopically implanted in the liver. In conclusion, our results support the hypothesis that cytostatic bile acid derivatives such as BANB-6 may offer a useful pharmacological strategy for the treatment of tumors of the enterohepatic circuit.
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Ácidos y Sales Biliares/farmacología , Supervivencia Celular/efectos de los fármacos , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Ácidos y Sales Biliares/síntesis química , Ácidos y Sales Biliares/química , Ácidos y Sales Biliares/uso terapéutico , Carcinoma Hepatocelular , Supervivencia Celular/fisiología , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Ratas , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To review the state of the art of robotic-aided hand physiotherapy for post-stroke rehabilitation, including the use of brain-machine interfaces. Each patient has a unique clinical history and, in response to personalized treatment needs, research into individualized and at-home treatment options has expanded rapidly in recent years. This has resulted in the development of many devices and design strategies for use in stroke rehabilitation. METHODS: The development progression of robotic-aided hand physiotherapy devices and brain-machine interface systems is outlined, focussing on those with mechanisms and control strategies designed to improve recovery outcomes of the hand post-stroke. A total of 110 commercial and non-commercial hand and wrist devices, spanning the 2 major core designs: end-effector and exoskeleton are reviewed. RESULTS: The growing body of evidence on the efficacy and relevance of incorporating brain-machine interfaces in stroke rehabilitation is summarized. The challenges involved in integrating robotic rehabilitation into the healthcare system are discussed. CONCLUSION: This review provides novel insights into the use of robotics in physiotherapy practice, and may help system designers to develop new devices.
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Interfaces Cerebro-Computador/estadística & datos numéricos , Traumatismos de la Mano/rehabilitación , Robótica/métodos , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Humanos , Accidente Cerebrovascular/patologíaRESUMEN
INTRODUCTION: Complicated community-acquired intra-abdominal infections (CA-cIAI) are a common cause of acute abdomen. OBJECTIVE: To identify the clinical and microbiology profile of CA-cIAI in four Colombian hospitals. METHODS: This is a prospective, descriptive study, between 08-2012 and 09-2014, including patients with CA-cIAI > 15 years. Data collected included: socio-demographic, clinical, diagnosis, and isolates of the first culture obtained aseptically during surgery with antimicrobial susceptibility. RESULTS: 192 patients were included, 62% men, median age 47.3 years. Co-morbidities were present in 38.4%, 13% had been hospitalized in the previous year 13%, and 9.4% had received antibiotics in the last 6 months; 44.3% were admitted for appendicitis, 17.7% for peritonitis and 16.7% for bowel perforation. CA-cIAI were assessed as moderate in 64.1% of the cases and were treated with ampicillin/sulbactam (SAM) and ertapenem. In 70.8% of cases a bacteria was isolated: 65.1% were gramnegative rods (80.0% Escherichia coli, 44.8% of them susceptible to pipercillin/tazobactam, 65.7% to SAM; 11.2 % were K.pneumoniae, 85% was susceptible for SAM; 16.7% were grampositive cocci (28.1% Streptococci viridans group). The median hospital stay was 7 days and 15.1% died. CONCLUSIONS: E. coli, K. pneumoniae and S. viridans were the main organisms to consider in an empiric therapy for CA-cIAI and it is important to know the local epidemiology in order to choose the right antibiotic.
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Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Infecciones Intraabdominales/epidemiología , Infecciones Intraabdominales/microbiología , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Colombia/epidemiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Farmacorresistencia Bacteriana , Femenino , Humanos , Infecciones Intraabdominales/tratamiento farmacológico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Factores Socioeconómicos , Estadísticas no ParamétricasRESUMEN
Toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may be formed during remediation of chlorinated phenols via Fenton oxidation. To highlight the need for monitoring the production of toxic byproducts in these reactions, this work assessed the influence of iron dose (0.09-0.36 mM) on the Fenton oxidation of 2-chlorophenol (2-CP, 15.56 mM), a potential precursor of PCDD/Fs, by quantifying 2-CP removal and mineralization rates as well as byproducts yields, including PCDD/Fs. Although the increase in the iron dose showed positive contribution to 2-CP oxidation, under the operating conditions of the current study (H2O2 at 20% of the stoichiometric dose and 20 °C), there was no effect on the mineralization rate, and TOC and chlorine balances were far to be closed, depicting the presence of chlorinated organic byproducts in the reaction medium. After 4 h of treatment, the total PCDD/Fs concentrations increased by 14.5-39 times related to the untreated sample when the iron doses tested decreased from 0.36 to 0.09 mM, with preferential formation of PCDFs over PCDDs and dominance of lower chlorinated congeners such as tetra and penta-PCDD/Fs. The treatment with the highest iron dose (0.36 mM) exhibited the lowest PCDD/Fs yields and was thus most successful at mitigating toxic byproducts of the Fenton oxidation, leading to lower sample toxic equivalence (TEQ) value.
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Benzofuranos/análisis , Clorofenoles/química , Peróxido de Hidrógeno/química , Hierro/química , Dibenzodioxinas Policloradas/análogos & derivados , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Benzofuranos/química , Dibenzofuranos Policlorados , Oxidación-Reducción , Dibenzodioxinas Policloradas/análisis , Dibenzodioxinas Policloradas/química , Contaminantes Químicos del Agua/química , Purificación del AguaRESUMEN
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are a family of unintentionally produced persistent organic pollutants (POPs) that have received considerable public and scientific attention due to the toxicity of some of their congeners, more specifically those with chlorine substitution in the 2,3,7,8 positions. The environmental management and control of PCDD/Fs is addressed at a global level through the Stockholm Convention that establishes that POPs should be destroyed or irreversibly transformed in order to reduce or eliminate their release to the environment. Several technologies, including advanced oxidation processes (AOPs) such as photolysis, photocatalysis and Fenton oxidation, have been considered as effective methods for destroying PCDD/Fs in polluted waters. Nevertheless, during the remediation of wastewaters it is critical that the treatment technologies applied do not lead to the formation of by-products that are themselves POPs, especially if PCDD/Fs precursors or chlorine are present in the reaction medium. Despite the high effectiveness of AOPs in the oxidation of major contaminants, scarce references deal with the monitoring of PCDD/Fs in the course of the oxidation process, revealing that a detailed assessment of non-combustion technologies with respect to PCDD/Fs formation is still lacking. This study reports a review of the state of the art related to the potential remediation and/or formation of PCDD/Fs as a result of the application of AOPs for the treatment of polluted waters, warning on the correct selection of the operating conditions.
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Benzofuranos/química , Dioxinas/química , Eliminación de Residuos Líquidos , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Oxidación-ReducciónRESUMEN
INTRODUCTION: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. OBJECTIVE: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. METHODS: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. RESULTS: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%. CONCLUSIONS: The introduction of ES could achieve greater adherence to a model of active surveillance, standardized and prospective, helping to improve the validity and quality of the recorded information.
INTRODUCCIÓN: Las infecciones asociadas a la atención en salud (IAAS) son un reto para la seguridad del paciente. Los comités de infecciones hospitalarios (CIH) deben realizar una vigilancia epidemiológica (VE) de las IAAS siguiendo los criterios de los Centros para el Control y Prevención de Enfermedades - EE.UU (CDC). La VE manual afecta la sensibilidad y especificidad del sistema de vigilancia, mientras que la VE electrónica mejora el desempeño, calidad y trazabilidad de la información registrada. OBJETIVO: Evaluar la implementación de una estrategia para la VE electrónica de las IAAS, resistencia bacteriana, consumo de antimicrobianos y características de los CIH en 23 clínicas y hospitales de alta complejidad en Colombia, en el periodo 2012-2013. MÉTODOS: Se realizó un estudio observacional descriptivo de la introducción de herramientas informáticas en los CIH, evaluando la estructura y funcionamiento de los CIH, el grado de incorporación del software HAI Solutions y la cumplimiento al registro de la información requerida. RESULTADOS: El 38% de las clínicas y hospitales (8/23) presentaron estrategias de vigilancia epidemiológica activa con criterios estándar del CDC. El 87% de las instituciones se adhirieron al módulo de captación de casos del software HAI Solutions, y el cumplimiento del diligenciamiento de los factores de riesgo de las IAAS asociadas a dispositivos fue del 33%. CONCLUSIONES: La introducción del modelo de VE electrónica podría lograr un mayor cumplimiento a un modelo de vigilancia epidemiológica activo, estandarizado y prospectivo, contribuyendo al mejoramiento en la validez y calidad de la información registrada.
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Infección Hospitalaria/epidemiología , Monitoreo Epidemiológico , Control de Infecciones/métodos , Programas Informáticos , Antiinfecciosos/administración & dosificación , Antiinfecciosos/uso terapéutico , Colombia/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/prevención & control , Farmacorresistencia Bacteriana , Humanos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
This work assesses the influence of the operating conditions H2O2 dose (20 or 100% of the stoichiometric amount), temperature (20 or 70°C), and the presence of chloride in the oxidation medium in the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during Fenton treatment of aqueous samples of 2-chlorophenol, 2-CP, one of the strongest precursor of PCDD/Fs. After 4h of oxidation in the experiments carried out with 20% H2O2 chlorinated phenoxyphenols and biphenyls, which are intermediates in PCDD/Fs formation, as well as PCDD/Fs were observed, resulting in concentrations 11 times higher than in the untreated sample. Additionally, when NaCl was also present in the reaction medium, PCDD/Fs were formed at higher extent, with a total concentration 74.4 times higher than in the untreated 2-CP solution. Results depicted a preferential formation of PCDFs over PCDDs, with dominance of lower chlorinated PCDD/Fs (tetra and penta-PCDD/Fs). Besides, the formation of the most toxic PCDD/Fs congeners (2,3,7,8-PCDD/Fs) was not favored under the operating conditions used in this work.
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Benzofuranos/química , Clorofenoles/química , Peróxido de Hidrógeno/química , Hierro/química , Dibenzodioxinas Policloradas/análogos & derivados , Cloruros/química , Oxidación-Reducción , Dibenzodioxinas Policloradas/química , TemperaturaRESUMEN
INTRODUCTION: The continuous evolution of antimicrobial resistance poses a major threat to public health worldwide. Molecular biology techniques have been integrated to epidemiological surveillance systems to improve the control strategies of this phenomenon. OBJECTIVE: To describe the phenotypic and molecular profiles of the most important Gram negative bacilli from intensive care units in 23 Colombian hospitals during the study period 2009-2012. MATERIALS AND METHODS: A descriptive study was conducted in 23 hospitals belonging to the Colombian Nosocomial Resistance Study Group. A total of 38.048 bacterial isolates were analyzed using WHONET over a four-year period. The antimicrobial resistant profiles were described for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii . Polymerase chain reaction was performed in 1.248 strains to detect the most clinically relevant carbapenemases. RESULTS: Escherichia coli was the most frequently isolated organism (mean=14.8%). Frequency of K. pneumoniae increased significantly from 11% in 2009 to 15% in 2012 (p<0.001). All screened isolates had rising trends of multidrug-resistant profiles. KPC ( Klebsiella pneumoniae carbapenemase) was detected in 68.4% of K. pneumoniae isolates while VIM (Verona integron-encoded metallo-betalactamase) was present in 46.5% of them. CONCLUSION: In this study, an increase in the trend of multidrug-resistant organisms and a wide distribution of carbapenemases was observed. The integration of molecular biology to surveillance systems allowed the compilation of this data, which will aid in the construction of guidelines on antimicrobial stewardship for prevention in Colombia.
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Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/aislamiento & purificación , Adulto , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , Niño , Preescolar , Colombia/epidemiología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Lactante , Recién Nacido , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/aislamiento & purificación , Vigilancia de la Población/métodos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/aislamiento & purificación , beta-Lactamasas/genéticaRESUMEN
Resumen Introducción: Ertapenem ha demostrado eficacia frente a Enterobacteriaceae productoras de β-lactamasas de espectro extendido, pero carece de actividad contra bacterias no fermentadoras; el desescalamiento a este antimicrobiano cuando no existe la presencia de P. aeruginosa podría reducir la presión selectiva contra esta bacteria y mejorar los resultados clínicos. Objetivo: Evaluar el impacto clínico del desescalamiento de antimicrobianos con cobertura anti-pseudomonas a ertapenem, un agente sin este espectro, en pacientes críticos con infecciones por Enterobacteriaceae. Métodos: Se realizó un estudio de cohorte prospectivo en adultos admitidos a Unidades de Cuidado Intensivo (UCI) con infecciones por Enterobacteriaceae, que habían sido desescalados de una cobertura anti-pseudomonas, a un antimicrobiano sin la misma (ertapenem). Se realizó un modelo de riesgo proporcional de Cox comparando mortalidad por cualquier causa y duración de estancia hospitalaria entre aquellos pacientes que permanecieron con cobertura anti-pseudomonas versus aquellos que fueron desescalados a ertapenem. Resultados: 105 pacientes en el grupo anti-pseudomonas fueron comparados con 148 pacientes del grupo de desescalamiento a ertapenem. El desescalamiento estuvo asociado con una menor mortalidad por cualquier causa comparado con los pacientes que permanecieron con cobertura anti-pseudomonas (hazard ratio ajustado 0,24; IC 95%: 0,12-0,46). La estancia hospitalaria en UCI fue similar en ambos grupos. Discusión: Los pacientes de UCI con infecciones por Enterobacteriaceae desescalados a terapia con ertapenem, tuvieron mejores resultados clínicos comparados con aquellos que permanecieron en terapia anti-pseudomonas, sugiriendo que el desescalamiento es una práctica segura en esta población.
Background: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. Aim: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. Methods: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. Results: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. Discussion: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Ertapenem/administración & dosificación , Unidades de Cuidados Intensivos , Antibacterianos/administración & dosificación , Pseudomonas/efectos de los fármacos , Factores de Tiempo , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento , Enfermedad Crítica , Colombia , Estadísticas no Paramétricas , Infecciones por Enterobacteriaceae/mortalidad , Estimación de Kaplan-Meier , Tiempo de InternaciónRESUMEN
Objetivo: describir el uso de ertapenem y las características clínico-microbiológicas de los pacientes durante la admisión en centro de cuarto nivel de complejidad en Medellín, Colombia entre 2009 y 2012. Materiales y métodos: estudio descriptivo retrospectivo en pacientes que recibieron ertapenem como terapia antibiótica. Resultados: 1390 historias clínicas revisadas, 835 cumplieron criterios de selección. Ertapenem se usó un 36,9% para manejo de infecciones urinarias y 28,1% en infección intraabdominal principalmente; en 84% se realizó cultivo microbiológico y en 80% se aisló algún germen, entre ellos 42,5% E. coli, 24,3% K. pneumoniae y 5,8% P. mirabilis. Las cepas Beta Lactamasa de Espectro Extendido de E. coli y K. pneumoniae fueron 39,8% y 57% respectivamente. La susceptibilidad a ertapenem en E. coli fue de 96,6% y K. pneumoniae 94,4%. Conclusiones: ertapenem ofrece resultados clínicos favorablesen el manejo de infecciones urinarias e intraabdominales. Es una alternativa para el manejo empírico de infecciones de origen comunitario y como terapia dirigida en infecciones hospitalarias..(AU)
Objective: to describe the use of ertapenem along with the clinical and microbiological characteristics of patients during their admission to a fourth-level health care facility in Medellin, Colombia between 2009 and 2012. Materials and Methods: a descriptive retrospective study on patients that were given antibiotic therapy with ertapenem.Results: 1390 clinical charts were reviewed, selecting 835 according to selection criteria. Ertapenem was prescribed in 36,9% for urinary tract infections and 28,1% for intraabdominal infections; 60% of the patients were located on general wards at the time of treatment with ertapenem. Microbiological cultures were performed for 84% of patients and 80% of those were positive, with 42,5% E. coli, 24,3% K. pneumoniae and 5,8% P. mirabilis. Extended spectrum betalactamases were found in 39,8% of the E. coli and 57% K. pneumoniae strains. Susceptibility of E. coli strains to ertapenem was 96,6% and 94,4% for K. pneumoniae. Conclusions: ertapenem offers favorable results when used for the treatment of urinary tract and intraabdominal infections. It is an alternative for empirical management of infections acquired outside the hospital setting, and and as directed therapy in hospital infections..(AU)
Asunto(s)
Humanos , Profilaxis Antibiótica , Control de Medicamentos en Pacientes en TránsitoRESUMEN
Introducción: La infección intra-abdominal complicada adquirida en la comunidad (IIAc-AC) es una causa frecuente de abdomen agudo. Objetivo: Identificar el perfil clínico y microbiológico de la IIAc-AC en cuatro hospitales de Colombia. Métodos: Estudio descriptivo, prospectivo entre 07-2012 y 09-2014 en pacientes de 15 o más años con IIAc-AC. Se midieron las frecuencias de variables socio-demográficas, clínicas, diagnóstico, aislamientos y susceptibilidad antimicrobiana del primer cultivo obtenido asépticamente del sitio de infección. Resultados: 192 pacientes incluidos, 62% hombres, edad media 47,3 años; 38,4% con co-morbilidad, 13% hospitalizados en el último año y 9,4% recibieron antimicrobianos en los últimos seis meses. Fueron admitidos 44,3%, por apendicitis 17,7% por peritonitis y 16,7% por perforación intestinal. El 64,1% de las IIAc-AC fue moderada y tratada con ampicilina/sulbactam (SAM) y ertapenem. En 70,8% se aisló al menos un microorganismo en: 65,1% bacilos gramnegativos (80,0% Escherichia coli, 44,8% susceptible a piperacilina/tazobactam, 65,7% a SAM y 11,2% Klebsiella pneumoniae, 85% susceptibles a SAM) y en 16,7% especies grampositivas (28,1% Streptococcus grupo viridans). La mediana de hospitalización fue siete días y 15,1% fallecieron. Conclusión: Escherichia coli y K. pneumoniae en IIAc-AC son los principales microorganismos a cubrir en la terapia empírica y es necesario conocer la susceptibilidad antimicrobiana en cada región para seleccionar un tratamiento empírico adecuado.
Introduction: Complicated community-acquired intra-abdominal infections (CA-cIAI) are a common cause of acute abdomen. Objective: To identify the clinical and microbiology profile of CA-cIAI in four Colombian hospitals. Methods: This is a prospective, descriptive study, between 08-2012 and 09-2014, including patients with CA-cIAI > 15 years. Data collected included: socio-demographic, clinical, diagnosis, and isolates of the first culture obtained aseptically during surgery with antimicrobial susceptibility. Results: 192 patients were included, 62% men, median age 47.3 years. Co-morbidities were present in 38.4%, 13% had been hospitalized in the previous year 13%, and 9.4% had received antibiotics in the last 6 months; 44.3% were admitted for appendicitis, 17.7% for peritonitis and 16.7% for bowel perforation. CA-cIAI were assessed as moderate in 64.1% of the cases and were treated with ampicillin/sulbactam (SAM) and ertapenem. In 70.8% of cases a bacteria was isolated: 65.1% were gramnegative rods (80.0% Escherichia coli, 44.8% of them susceptible to pipercillin/tazobactam, 65.7% to SAM; 11.2 % were K.pneumoniae, 85% was susceptible for SAM; 16.7% were grampositive cocci (28.1% Streptococci viridans group). The median hospital stay was 7 days and 15.1% died. Conclusions: E. coli, K. pneumoniae and S. viridans were the main organisms to consider in an empiric therapy for CA-cIAI and it is important to know the local epidemiology in order to choose the right antibiotic.