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Despite their high gravimetric and volumetric energy densities, boron (B) particles suffer from poor oxidative energy release rates as the boron oxide (B2O3) shell impedes the diffusivity of O2 to the particle interior. Recent experiemental studies have shown that the addition of metals with a lower free energy of oxidation, such as Mg, can reduce the oxide shell of B and enhance the energetic performance of B by â¼30-60%. However, the exact underlying mechanism behind the reactivity enhancement is unknown. Here, we performed DFTB-MD simulations to study the reaction of Mg vapor with a B2O3 surface. We found that the Mg becomes oxidized on the B2O3 surface, forming a MgBxOy phase, which induces a tensile strain in the B-O bond at the MgBxOy-B2O3 interface, simultaneously reducing the interfacial B and thereby developing dangling bonds. The interfacial bond straining creates an overall surface expansion, indicating the presence of a net tensile strain. The B with dangling bonds can act as active centers for gas-phase O2 adsorption, thereby increasing the adsorption rate, and the overall tensile strain on the surface will increase the diffusion flux of adsorbed O through the surface to the particle core. As the overall B particle oxidation rate is dependent on both the O adsorption and diffusion rates, the enhancement in both of these rates increases the overall reactivity of B particles.
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Semi-empirical quantum models such as Density Functional Tight Binding (DFTB) are attractive methods for obtaining quantum simulation data at longer time and length scales than possible with standard approaches. However, application of these models can require lengthy effort due to the lack of a systematic approach for their development. In this work, we discuss the use of the Chebyshev Interaction Model for Efficient Simulation (ChIMES) to create rapidly parameterized DFTB models, which exhibit strong transferability due to the inclusion of many-body interactions that might otherwise be inaccurate. We apply our modeling approach to silicon polymorphs and review previous work on titanium hydride. We also review the creation of a general purpose DFTB/ChIMES model for organic molecules and compounds that approaches hybrid functional and coupled cluster accuracy with two orders of magnitude fewer parameters than similar neural network approaches. In all cases, DFTB/ChIMES yields similar accuracy to the underlying quantum method with orders of magnitude improvement in computational cost. Our developments provide a way to create computationally efficient and highly accurate simulations over varying extreme thermodynamic conditions, where physical and chemical properties can be difficult to interrogate directly, and there is historically a significant reliance on theoretical approaches for interpretation and validation of experimental results.
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STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group 4991 versus 5262 in the HSG group, mean cost difference = -271 (95% CI -273 to -269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary. STUDY FUNDING/COMPETING INTEREST(S): The authors received no external financial support for the research. B.W.J.M. is supported by an NHMRC Investigator Grant (GNT1176437). B.W.J.M. reports consultancy for ObsEva, Merck KGaA, Guerbet. B.W.J.M. reports receiving travel support from Merck KGaA. C.T.P. reports consultancy for Guerbet, outside of this manuscript. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NTR3462.
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Histerosalpingografía , Infertilidad , Femenino , Humanos , Embarazo , Tasa de Natalidad , Análisis Costo-Beneficio , Nacimiento VivoRESUMEN
BACKGROUND: Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. METHODS: The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. RESULTS: Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. CONCLUSION: Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.
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Procedimientos Quirúrgicos del Sistema Biliar , Colestasis , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Biopsia/efectos adversos , Biopsia/métodos , Colestasis/diagnóstico por imagen , Colestasis/etiología , Consenso , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , HumanosRESUMEN
OBJECTIVES: We aimed to compare the effectiveness of antiretroviral therapy (ART) classes for achieving HIV RNA suppression to < 50 HIV-1 RNA copies/mL within 6 months of initiation with high viral loads (VLs). Secondary objectives were to compare viral suppression (VS) at 12 weeks and 12 months, partial HIV RNA suppression to < 200 copies/mL, time to VS, time to rebound, and change in CD4 cell count. METHODS: This was a multicentre, retrospective, observational study. Adult patients were included if they initiated ART between January 2005 and December 2016 with a VL ≥ 100 000 copies/mL. RESULTS: There were 220 patients included in the study. The median VL was 252 919 [interquartile range (IQR) 149 472-500 000] copies/mL. Nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients were more likely to achieve VS by 6 months compared to those initiating ART containing protease inhibitors (PIs) [75.4% vs. 44.1%, respectively; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.62-6.90] or integrase strand transfer inhibitors (INSTIs) (75.4% vs. 55.8%, respectively; OR 2.40; 95% CI 1.03-5.58). VS at 12 weeks was more frequent with INSTI-containing regimens than with PIs (28.9% vs. 9.0%, respectively; OR 4.10; 95% CI 1.69-9.92). VS at 12 months did not significantly differ between treatment regimens. Median time to complete VS for INSTI, PI and NNRTI recipients was 22.3 (95% CI 13.4-33), 30.1 (95% CI 25-36) and 19.9 (95% CI 16-22.3) weeks, respectively. There were no significant differences in time to viral rebound or change in CD4 cell counts. CONCLUSIONS: Patients with high VLs initiated on NNRTIs were more likely to achieve VS by 6 months on ART compared to INSTI and PI recipients.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral/efectos de los fármacos , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga Viral/estadística & datos numéricosRESUMEN
Purpose: To describe and evaluate a novel technique for eyelid margin repair without the use of marginal sutures.Methods: A retrospective chart review of patients who underwent primary repair of full-thickness lid margin defects using the described technique between March 2013 and May 2019 was performed. Clinical data such as indication for repair as well as size of defect was analyzed. The primary outcome measures included presence or absence of lid notching and post-operative complications such as wound dehiscence, infection, eyelid malposition, and keratopathy. Descriptive statistics were used.Results: A total of 31 cases were identified. Five were excluded in post-operative analysis for follow-up of less than 2 weeks. The average age was 59.6 years (range 22-88) and 54.8% of patients were female. Average follow up in post-operative analysis group was 17.0 weeks (range 2 weeks to 42 months). Average defect size was 5.77 mm (range 2-12 mm). Reasons for repair were resection of eyelid lesion in 25/31 (80.6%), floppy eyelid in 4/31 (12.9%), trauma in 1/31 (3.2%), and trichiasis in 1/31 (3.2%). Post-operative eyelid notching was noted in 2/26 patients (7.7%), and there were no instances of wound dehiscence, infection, eyelid malposition, or keratopathy noted.Conclusions: Our technique for full-thickness eyelid margin repair without the use of marginal sutures successfully repairs defects up to 12 mm for various indications. We observed comparable cosmetic outcomes to previously described techniques as well as a low rate of complications using our technique.
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Blefaroplastia , Enfermedades de los Párpados , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Párpados/cirugía , Párpados/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Suturas , Resultado del Tratamiento , Adulto JovenRESUMEN
Computer simulations are carried out to characterize the variation of spin-crossover (SCO) behavior of the prototypical {Fe(pz)[Pt(CN)4]} metal-organic framework (MOF) upon adsorption of chemically and structurally different guest molecules. A detailed analysis of both strength and anisotropy of guest molecule-framework interactions reveals direct correlations between the mobility of the guest molecules inside the MOF pores, the rotational mobility of the pyrazine rings of the framework, and the stabilization of the low-spin state of the material. On the basis of these correlations, precise molecular criteria are established for predicting the spin state of {Fe(pz)[Pt(CN)4]} upon guest adsorption. Finally, predictions of the SCO temperature upon adsorption of various toxic gases demonstrate that in silico modeling can provide fundamental insights and design principles for the development of spin-crossover MOFs for applications in gas detection and chemical sensing.
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Metal-organic frameworks (MOFs) have emerged as a versatile platform for the rational design of multifunctional materials, combining large specific surface areas with flexible, periodic frameworks that can undergo reversible structural transitions, or "breathing", upon temperature and pressure changes, and through gas adsorption/desorption processes. Although MOF breathing can be inferred from the analysis of adsorption isotherms, direct observation of the structural transitions has been lacking, and the underlying processes of framework reorganization in individual MOF nanocrystals is largely unknown. In this study, we describe the characterization and elucidation of these processes through the combination of in situ environmental transmission electron microscopy (ETEM) and computer simulations. This combined approach enables the direct monitoring of the breathing behavior of individual MIL-53(Cr) nanocrystals upon reversible water adsorption and temperature changes. The ability to characterize structural changes in single nanocrystals and extract lattice level information through in silico correlation provides fundamental insights into the relationship between pore size/shape and host-guest interactions.
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Estructuras Metalorgánicas/ultraestructura , Microscopía Electrónica de Transmisión/métodos , Cromo/química , Simulación por Computador , Estructuras Metalorgánicas/química , Modelos Moleculares , Nanopartículas/química , Nanopartículas/ultraestructura , Porosidad , Temperatura , Agua/químicaRESUMEN
Vancomycin is one of the most commonly utilized antibiotics in US hospitals. It remains the drug of choice for the treatment of serious infections caused by methicillin-resistant Staphylococcus aureus. For many of these deep-seated infections, guidelines recommend achieving troughs of 15-20 mg/L for treatment efficacy. At our institution we observed a number of cases of presumed vancomycin-induced acute tubular necrosis clinically diagnosed by the nephrology service. We report eight cases of presumed vancomycin-induced acute tubular necrosis, three of which required hemodialysis before resolution of nephrotoxicity. Only three of the eight patients received nephrotoxins prior to development of nephrotoxicity. All eight patients ultimately recovered renal function following discontinuation.
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Lesión Renal Aguda/inducido químicamente , Antibacterianos/efectos adversos , Vancomicina/efectos adversos , Adulto , Antibacterianos/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Persona de Mediana Edad , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/uso terapéutico , Adulto JovenRESUMEN
The rational design of multifunctional materials with properties that can be selectively controlled at the molecular level is key to the development and application of nanoscale devices. In this study, molecular dynamics simulations using ligand-field molecular mechanics are performed to elucidate, for the first time, the molecular mechanisms responsible for the variation of the spin-crossover properties of the {Fe(pz)[Pt(CN)4]} metal-organic framework upon water adsorption. The simulations demonstrate a direct relationship between the water loading adsorbed in the pores and the variation of the spin-crossover transition temperature, with the high-spin state of the material becoming gradually more stabilized as the number of adsorbed water molecules increases. The decrease of the spin-crossover temperature of {Fe(pz)[Pt(CN)4]} upon water adsorption predicted by the simulations is in agreement with the available experimental data and is traced back to the elongation of the bonds between the Fe(II) atoms and the organic linkers induced by interactions of the adsorbed water molecules with the framework.
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The MB-pol many-body potential has recently emerged as an accurate molecular model for water simulations from the gas to the condensed phase. In this study, the accuracy of MB-pol is systematically assessed across the three phases of water through extensive comparisons with experimental data and high-level ab initio calculations. Individual many-body contributions to the interaction energies as well as vibrational spectra of water clusters calculated with MB-pol are in excellent agreement with reference data obtained at the coupled cluster level. Several structural, thermodynamic, and dynamical properties of the liquid phase at atmospheric pressure are investigated through classical molecular dynamics simulations as a function of temperature. The structural properties of the liquid phase are in nearly quantitative agreement with X-ray diffraction data available over the temperature range from 268 to 368 K. The analysis of other thermodynamic and dynamical quantities emphasizes the importance of explicitly including nuclear quantum effects in the simulations, especially at low temperature, for a physically correct description of the properties of liquid water. Furthermore, both densities and lattice energies of several ice phases are also correctly reproduced by MB-pol. Following a recent study of DFT models for water, a score is assigned to each computed property, which demonstrates the high and, in many respects, unprecedented accuracy of MB-pol in representing all three phases of water.
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We report two patients who presented with Brown's syndrome. The first is a 7-year-old boy who at the time of his diagnosis was also found to have enthesitis and HLA-B27 positivity. The second patient was diagnosed with bilateral Brown's syndrome at 13 months of age. At age 7 she developed a persistent oligoarticular arthritis and unilateral anterior iritis consistent with the oligoarticular Juvenile Idiopatic Arthritis (JIA) phenotype. These cases highlight ophthalmologic findings and diagnostic considerations with respect to Brown's syndrome and associated childhood onset rheumatologic disease.
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Artritis Juvenil/complicaciones , Trastornos de la Motilidad Ocular/etiología , Artritis Juvenil/diagnóstico , Artritis Juvenil/inmunología , Niño , Femenino , Antígeno HLA-B27/inmunología , Humanos , MasculinoRESUMEN
This study investigated the main factors influencing digester temperature and methods to reduce heat losses during the cold season in the subtropics. Four composite digesters (two insulated and two uninsulated) were buried underground to measure their internal temperature (°C) at a depth of 140 cm and 180 cm, biogas production and methane (CH4) concentration in biogas from August to February. In parallel the temperature of the air (100 cm above ground), in the slurry mixing tank and in the soil (10, 100, 140, and 180 cm depth) was measured by thermocouple. The influent amount was measured daily and the influent chemical composition was measured monthly during the whole experimental period. Seasonal variations in air temperature significantly affected the temperature in the soil, mixing tank and digester. Consequently, biogas production, which is temperature dependent, was influenced by the season. The main factors determining the internal temperature in the digesters were insulation with Styrofoam, air temperature and temperature of slurry in the mixing tank. Biogas production is low due to the cold climate conditions in winter in Northern Vietnam, but the study proved that storing slurry in the mixing tank until its temperature peak at around 14:00 h will increase the temperature in the digester and thus increase potential biogas production. Algorithms are provided linking digester temperature to the temperature of slurry in the mixing tank.
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In developing countries, biogas energy production is seen as a technology that can provide clean energy in poor regions and reduce pollution caused by animal manure. Laboratories in these countries have little access to advanced gas measuring equipment, which may limit research aimed at improving local adapted biogas production. They may also be unable to produce valid estimates of an international standard that can be used for articles published in international peer-reviewed science journals. This study tested and validated methods for measuring total biogas and methane (CH4) production using batch fermentation and for characterizing the biomass. The biochemical methane potential (BMP) (CH4 NL kg(-1) VS) of pig manure, cow manure and cellulose determined with the Moller and VDI methods was not significantly different in this test (p>0.05). The biodegradability using a ratio of BMP and theoretical BMP (TBMP) was slightly higher using the Hansen method, but differences were not significant. Degradation rate assessed by methane formation rate showed wide variation within the batch method tested. The first-order kinetics constant k for the cumulative methane production curve was highest when two animal manures were fermented using the VDI 4630 method, indicating that this method was able to reach steady conditions in a shorter time, reducing fermentation duration. In precision tests, the repeatability of the relative standard deviation (RSDr) for all batch methods was very low (4.8 to 8.1%), while the reproducibility of the relative standard deviation (RSDR) varied widely, from 7.3 to 19.8%. In determination of biomethane concentration, the values obtained using the liquid replacement method (LRM) were comparable to those obtained using gas chromatography (GC). This indicates that the LRM method could be used to determine biomethane concentration in biogas in laboratories with limited access to GC.
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BACKGROUND: TB control remains a serious public health problem, compounded by poor treatment adherence, which increases the likelihood of onward transmission. We evaluated the effectiveness of medication event reminder monitoring (MERM) upon treatment adherence in a high TB burden setting.METHODS: We conducted an open-label parallel group randomised controlled trial among pulmonary TB adults. Participants were provided with a MERM device to store their medications. In the intervention arm, the devices were set to provide daily medication intake reminders. Primary outcome was the proportion of patient-months in which at least 6/30 doses were missed. Secondary outcomes included 1) the proportion of patient-months in which at least 14/30 doses were missed, and 2) the proportion of doses missed.RESULTS: Of 2,142 patients screened, 798 (37.3%) met the inclusion criteria and 250 participants were enrolled. The mean ratio (MR) for poor adherence between the intervention and control groups was 0.72 (95% CI 0.55-0.86). The intervention was also associated with a reduction in the proportion of patients missing at least 14/30 doses (MR 0.61, 95% CI 0.54-0.68) and the percentage of total doses missed (MR 0.75, 95% CI 0.68-0.80).CONCLUSION: MERM is effective in improving TB treatment adherence in a resource-limited environment.
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Cumplimiento de la Medicación , Tuberculosis Pulmonar , Adulto , Humanos , Sistemas Recordatorios , Tuberculosis Pulmonar/tratamiento farmacológico , Monitoreo de DrogasRESUMEN
PURPOSE: Point-of-care ultrasonography (POCUS) is an established tool in the management of hypotensive patients in the emergency department (ED). We compared the diagnostic accuracy of a POCUS protocol versus standard assessment without POCUS in patients with undifferentiated hypotension. METHODS: This was an international, multicenter randomized controlled trial included three EDs in North America and three in South Africa from September 2012 to December 2016. Hypotensive patients were randomized to early POCUS protocol plus standard care (POCUS group) or standard care without POCUS (control group). Initial and secondary diagnoses were recorded at 0 and 60 min. The main outcome was measures of diagnostic accuracy of a POCUS protocol in differentiating between cardiogenic and non-cardiogenic shock. Secondary outcomes were diagnostic performance for shock sub-types, as well as changes in perceived category of shock and overall diagnosis. RESULTS: Follow-up was completed for 270 of 273 patients. For cardiogenic shock, the POCUS-based diagnostic approach (POCUS) performed similarly to the non-POCUS approach (control) for specificity [95.5% (89.9-98.5) vs.93.8% (87.7-97.5)]; positive likelihood ratio (17.92 vs 14.80); negative likelihood ratio (0.21 vs 0.09) and diagnostic odds ratio (85.6 vs 166.57), with a similar overall diagnostic accuracy between the two approaches [93.7% (88-97.2) vs 93.6% (87.8-97.2)]. Diagnostic performance measures were similar across sub-categories of shock. CONCLUSION: This is the first randomized controlled trial to compare diagnostic performance of a POCUS protocol to standard care without POCUS in undifferentiated hypotensive ED patients. POCUS performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test; however, performance did not differ meaningfully from standard assessment.
RéSUMé: OBJECTIF: L'échographie au point d'intervention (POCUS) est un outil bien établi dans la gestion des patients hypotendus dans le service des urgences. Nous avons comparé la précision diagnostique d'un protocole POCUS par rapport à une évaluation standard sans POCUS chez des patients présentant une hypotension indifférenciée. MéTHODES: Il s'agissait d'un essai contrôlé randomisé international multicentrique incluant 3 services d'urgence en Amérique du Nord et 3 en Afrique du Sud de septembre 2012 à décembre 2016. Les patients hypotenseurs ont été répartis par randomisation selon le protocole POCUS précoce plus les soins standard (groupe POCUS) ou les soins standard sans POCUS (groupe témoin). Les diagnostics initiaux et secondaires ont été enregistrés à 0 et 60 minutes. Le principal résultat était la mesure de la précision diagnostique d'un protocole POCUS pour différencier le choc cardiogénique du choc non cardiogénique. Les résultats secondaires étaient la performance diagnostique pour les sous-types de chocs, ainsi que les changements dans la perception de la catégorie de choc et du diagnostic global. RéSULTATS: Le suivi a été complété pour 270 des 273 patients. Pour le choc cardiogénique, l'approche diagnostique basée sur le POCUS (POCUS) a donné des résultats similaires à l'approche non-POCUS (Contrôle) pour la spécificité (95,5 % (89,998,5) vs 93,8 % (87,797,5)) ; Rapport de vraisemblance positif (17,92 vs 14,80) ; Le rapport de vraisemblance négatif (0,21 vs 0,09) et le rapport de cotes diagnostiques (85,6 vs 166,57), avec une précision diagnostique globale similaire entre les deux approches (93,7 % (8897,2) vs 93,6 % (87,897,2). Les mesures de performance diagnostique étaient similaires dans toutes les sous-catégories de choc. CONCLUSION: Il s'agit du premier essai contrôlé randomisé visant à comparer la performance diagnostique d'un protocole POCUS aux soins standard sans POCUS chez des patients hypotendus indifférenciés aux urgences. La POCUS a donné de bons résultats diagnostiques chez les patients hypotendus indifférenciés, surtout en tant que test de référence ; cependant, les performances ne diffèrent pas de manière significative de l'évaluation standard.
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Hipotensión , Choque , Humanos , Sistemas de Atención de Punto , Ultrasonografía/métodos , Hipotensión/diagnóstico por imagen , Choque/diagnóstico por imagen , Servicio de Urgencia en Hospital , Choque CardiogénicoRESUMEN
OBJECTIVES: H2-receptor antagonists (H2RA) have been shown to reduce stress-related mucosal bleeding (SRMB), yet randomized controlled trials assessing proton pump inhibitors (PPIs) have yielded conflicting results. The objective of this study was to evaluate the efficacy of PPIs vs. H2RAs in the prophylaxis of SRMB in critically ill adults with risk factors for bleeding. METHODS: Tailored literature searches of the past four decades were conducted. Outcomes measured were the decreases in rates of clinically significant bleeding (B, primary outcome of the meta-analysis), nosocomial pneumonia (P), and mortality (M) (secondary outcomes). Study heterogeneity was sought and quantified. Results are reported as odd ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Eight fully published randomized controlled trials and five abstracts met the inclusion criteria. Prophylactic PPI administration significantly decreased the incidence of bleeding (N = 1,587 patients, OR = 0.30; 95% CI: 0.17-0.54), number needed to treat = 39; 95% CI: 21-303 with no observed statistical heterogeneity among the relevant comparisons (P = 0.93, I2 = 0.0%). No statistical differences were noted for the development of nosocomial pneumonia (n = 7, N = 1,017 patients, OR = 1.05; 95% CI: 0.69-1.62) or mortality (n = 8, N = 1,260 patients, OR = 1.19; 95% CI: 0.84-1.68) or (and no heterogeneity was found for either: P = 0.85, I2 = 0.0%, and P = 0.96, I2 = 0%, respectively). CONCLUSIONS: In critically ill patients at risk for the development of SRMB, PPI prophylaxis significantly decreased rates of clinically significant bleeding compared with H2RA, without affecting the development of nosocomial pneumonia or mortality rates. The magnitude of the beneficial effect, and its clinical relevance, now requires further characterization using cost-effectiveness analysis considering the incidence of stress-related mucosal disease-related bleeding.
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Enfermedad Crítica , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Estrés Psicológico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: The phosphoinositide 3-kinase (PI3K) signaling pathway is an interesting target in cancer treatment. The awareness of the proarrhythmic risk of PI3K inhibitors was raised because PI3K is also involved in regulating signaling toward cardiac ion channels. Canine cardiomyocytes treated with PI3K inhibitors show an increased action potential duration and reduced cardiac repolarizing currents. Now, the potential proarrhythmic effect of chronic treatment of PI3K/mTOR inhibitor GSK2126458 (omipalisib) was investigated in the atrioventricular (AV) block dog model. Methods: Purpose-bred Mongrel dogs received complete AV block by ablation of the bundle of His and their hearts were paced in the right ventricular apex at VDD-mode (RVA-VDD). In this way, sinus rhythm was maintained for 15 ± 1 days and thereby bradycardia-induced cardiac remodeling was prevented. Dogs received 1 mg/kg omipalisib once (n = 3) or twice (n = 10) a day via oral administration for 7 days. Under standardized conditions (anesthesia, bradycardia at 60 beats/min, and a dofetilide challenge), potential proarrhythmic effects of omipalisib were investigated. Results: Twice daily dosing of omipalisib increased accumulative plasma levels compared to once daily dosing accompanied with adverse events. Omipalisib prolonged the QT interval at baseline and more strongly after the dofetilide challenge (490 ± 37 to 607 ± 48 ms). The arrhythmic outcome after omipalisib resulted in single ectopic beats in 30% of dogs perpetuating in multiple ectopic beats and TdP arrhythmia in 20% of dogs. Isolated ventricular cardiomyocytes from omipalisib-treated dogs showed a diminished IKs current density. Conclusion: Chronic treatment of PI3K/mTOR inhibitor omipalisib prolonged the QT interval in a preclinical model under standardized proarrhythmic conditions. Furthermore, this study showed that electrical remodeling induced by omipalisib had a mild proarrhythmic outcome.
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BACKGROUND: Due to the corona pandemic and also to the new competence-oriented catalogue of learning objectives in medicine and the master plan for medical studies 2020, the development of digital and practical teaching concepts has experienced a great increase in importance. AIM OF THE WORK: As a result of this development, it was an important task to establish this combination and incorporate it into the curricular teaching process. MATERIAL AND METHODS: The "Toolkit dermatology" was established, which was sent to a total of more than 650 students at German university dermatology clinics. Using educational films, the students were able to practice their skills. In a further development, the toolkit was combined with classroom lectures and the students were asked to evaluate the toolkit online. RESULTS: The vast majority of students (95-100%) clearly stated that the toolkit helped them to develop their practical skills. Some of them were in fact motivated to complete a clinical traineeship/practical tertial year in dermatology (21-88%). The combination of toolkit and subsequent classroom teaching was also rated very positively (82.2%), as this hybrid mode of teaching provided a better understanding. DISCUSSION: Digital teaching formats as part of the concept of blended learning, i.e. the combination of virtual and analogue teaching formats, are becoming increasingly more important. Solutions for the disadvantages, such as the lack of real interaction and suitable examination formats, still remain to be found; however, the toolkit project demonstrates that hands-on and digital teaching can lead to high student motivation as well as a high educational standard.
Asunto(s)
Dermatología , Estudiantes de Medicina , Humanos , Dermatología/educación , Aprendizaje , MotivaciónRESUMEN
Density functional tight binding (DFTB) is an attractive method for accelerated quantum simulations of condensed matter due to its enhanced computational efficiency over standard density functional theory (DFT) approaches. However, DFTB models can be challenging to determine for individual systems of interest, especially for metallic and interfacial systems where different bonding arrangements can lead to significant changes in electronic states. In this regard, we have created a rapid-screening approach for determining systematically improvable DFTB interaction potentials that can yield transferable models for a variety of conditions. Our method leverages a recent reactive molecular dynamics force field where many-body interactions are represented by linear combinations of Chebyshev polynomials. This allows for the efficient creation of multi-center representations with relative ease, requiring only a small investment in initial DFT calculations. We have focused our workflow on TiH2 as a model system and show that a relatively small training set based on unit-cell-sized calculations yields a model accurate for both bulk and surface properties. Our approach is easy to implement and can yield reliable DFTB models over a broad range of thermodynamic conditions, where physical and chemical properties can be difficult to interrogate directly and there is historically a significant reliance on theoretical approaches for interpretation and validation of experimental results.