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Background and Objectives Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. Methods An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. Results A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. Conclusions We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

There is a paucity of data on the incidence and severity of tram tracks related cycling injuries. The aim of this study is to get insight into the incidence, severity and characteristics of tram tracks related cycling injuries, potentially defining significant 'hotspots' in the Ghent city area.A one-year, multicenter, prospective, observational study was conducted. Patients presenting to the emergency departments of all 4 Ghent hospitals with tram tracks related cycling injury, were included. Data on patient demographics, circumstances of the accident and type of injury were collected.149 patients were included, with a median age of 31 years. 42 patients had fractures, 39 patients required wound sutures, 79 and 49 patients suffered from bruising and abrasions respectively. Only 5 patients required admission. No patients died or suffered life-threatening injuries. Women (65.1%) presented more frequently than men (34.9%). Forty-tree percent of all accidents happened in autumn (Tram tracks are potentially dangerous and may lead to clinically important injuries and significant number of days off work.

Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen.An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets.A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets.We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

Objectives: Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. Material and methods: Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing. Results: Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. Conclusions: A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. Clinical relevance: Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

Background Despite the effectiveness of Participatory Action Research (PAR) in reducing the gap between evidence and practice, its use to improve care integration is rare. The aim is to analyze the factors influencing the implementation of PAR interventions to improve clinical coordination in public health services networks of Brazil, Chile, Colombia, Mexico and Uruguay. Methods A qualitative, descriptive-interpretative study was conducted in participating healthcare networks of each country. Focus groups and individual semi-structured interviews were conducted to a criteria sample of participants: members of Local Steering Committee (LSC)(29), professionals’ platform (PP)(28), other professionals (49) and managers(28). Thematic content analysis was performed, segmented by country and themes. Results Findings reveal that contextual factors, the PAR process and interventions’ content were determinants in the implementation, interacting over time, and differing among experiences. On the one hand, institutional support (providing the necessary resources) together with the interest of professionals and managers in participating, emerged as influencing factors influenced by other factors related to: the system (alignment with policies; electoral cycle), networks (lack of time due to work overload; precarious employment conditions) and individuals (limited mutual knowledge and mistrust). On the other, some characteristics of the PAR process facilitated institutional support and motivation: professionals’ participation in all activities, design flexibility and shared decision-making - also present when interventions were based on mutual adjustment - the LSC’s leadership and the facilitating role of the research team. Conclusions Evidence is provided that when some contextual elements converge the implementation of interventions through PAR processes can turn into a factor of motivation and cohesion, determinant for the adoption of clinical coordination interventions. Key messages Contributes to fill the knowledge gap in factors influencing the implementation of PAR interventions in healthcare. Provides a framework for analysis and recommendations for their implementation.

Toxic exposure to caustics and respiratory irritants. Toxic emergencies for which the ENT physician is con- sulted mainly involve toxic exposure of the upper airway and digestive tract to caustics and respiratory irritants. The ENT physician may, however, also be involved as a first responder in the case of poisoned patients. This article therefore aims to provide a comprehensive general approach to patients with suspected poisoning and to present a more elaborate discussion on the diagnosis and management of patients following exposure to caustics and respiratory irritants. This survey, however, does not intend to be a substitute for the need for consultation with an emergency physician and a clinical toxicologist qualified in the diagnosis and treatment of poisoned patients.

Detailed geological and geochemical characterization is crucial to support soil studies in such geologically and topographically complex systems as the Gilgel Gibe catchment in southwestern Ethiopia. Field studies, as well as mineralogical, petrological and geochemical analyses on selected rock samples and their weathering products revealed that the catchment is dominantly underlain by rhyolites and trachytes, which occur as both lava flows and pyroclastic associations. Most of the lavas have a trachytic texture, while few others are massive or show spherulitic or perlitic texture. The rocks have a SiO 2 -content ranging from about 62 to 73 wt% (intermediate to felsic composition, on an anhydrous base) and a relatively high Na 2 O + K 2 O content ranging from about 9 to 12 wt% (anhydrous base). The dominant phenocrysts present in the rocks are plagioclase, sanidine and Fe–Ti oxide minerals. Alkali-rich amphiboles and quartz occur in most of them, while hornblende, titanite and clinopyroxene are rare. The amount of phenocrysts varies from less than 1 vol.% to about 30 vol.%. The pyroclastic associations are discontinuously scattered within the study area. They all have a glassy matrix (vitrophyric texture) and are composed of a mixture of lithics, crystals and glass. In comparison with the lava samples, the pyroclastic samples exhibit a more variable chemistry. In contrast, the X-ray diffractograms of the pyroclastic deposits and the lavas show little difference. The Chemical Index of Alteration values for the studied samples vary from 53 to 99 indicating moderate to high intensity of weathering. Samples from lava flows have shown less degree of weathering than samples of the pyroclastic associations.

We present the case of a 27-year-old immunocompetent man who progressively developed a generalized lymphadenopathy and B symptoms. Results of Epstein-Barr virus (EBV) serology were suggestive for a past infection, but the EBV viral load in whole blood was high. Also, core needle biopsy of the largest lymph node showed an image which could fit an EBV-driven reactive lymphoproliferation. Despite the absence of an immune disorder, all medical evidence points to an EBV-driven lymphoproliferative proces. In immunocompetent patients, it seems extremely uncommon to detect a high EBV viral load in the absence of serological evidence of an acute EBV infection or reactivation. We reviewed literature on this topic and on the selection of the appropriate sample type for EBV PCR, as this is known to be a critical point. Serological testing for the diagnosis of EBV infection is the gold standard in immunocompetent patients. Measuring EBV viral load is only recommended when dealing with immunocompromised patients. Although extremely rare, this case report shows that there is a place for EBV PCR in certain situations in immunocompetent patients. Besides, there is still no consensus regarding the specimen of choice for the determination of the EBV viral load. The preferred specimen type seems to depend on the patient's underlying condition.

BackgroundResearch regarding the optimal amikacin (AMI) dosing regimen in critically ill children is scarce.1 Optimal AMI efficacy has been observed with plasma peak over minimal inhibitory concentration of the suspected pathogen (peak/MIC) ratios of 8 to 10. Plasma trough levels (Cmin) >5mcg/ml are related to its toxicity.The objectives of this pilot study were to: (1) evaluate target attainment rate and occurrence of supratherapeutic concentrations in early and assumed steady-state dose conditions, and (2) investigate the correlation between AMI clearance and estimated glomerular filtration (eGFR).MethodsChildren admitted to the ICU receiving intravenous AMI (20 mg/kg once daily) were included. Serial blood samples were obtained from early (1st/2nd) and assumed steady-state (SS) doses. The evaluated target peak concentration range was 54–64 mcg/ml, assuming a Pseudomonas aeruginosa infection with Eucast MIC breakpoint of 8 mg/L, and a Cmin threshold of 5 mcg/L. eGFR was estimated using the modified Schwartz formula. AMI clearance was calculated using noncompartmental PK analysis. Correlation was assessed by means of a scatter plot and Pearson Correlation Coefficient (r).ResultsTwenty-one patients (median age1,5 years; range:0,5 months-14 year, median eGFR 162 ml/min/1,73m2 (range:107–475 ml/min/1,73m2) were included. In early dose conditions, 69% of patients had therapeutic peak concentrations (median: 60 mcg/ml; range:26–73 mcg/ml). In SS conditions, 60% of patients had therapeutic peak concentrations (median: 59 mcg/ml; range:35–83 mcg/ml). Only one supratherapeutic Cmin was observed. AMI clearance (median 0.08L/h/kg; range: 0.05–0.91 L/h/kg) was comparable to what has been previously reported but showed no correlation with eGFR (r=0.1; p=0,66) [1].ConclusionThis pilot study suggest that the current AMI dosing regimen may lead to subtherapeutic concentrations in patients infected with less susceptible pathogens. Supratherapeutic Cmin were far less of a concern. Dose adjustments of renally cleared drugs based on eGFR may not be reliable in this patient population.ReferencesIllamola SM, Sherwin CM, van Hasselt JGC. Clinical Pharmacokinetics of Amikacin in Pediatric Patients: A Comprehensive review of Population Pharmacokinetic Analysis. Clin Pharmacokinet ( 2018) 57:1217.Disclosure(s)Nothing to disclose

BackgroundThe past years augmented renal clearance (ARC), observed in the critically ill paediatric population, has received an increased attention by researchers due to its major impact on drug exposure.1 Since a recent report demonstrated that the maturation of the glomerular filtration rate (GFR) in juvenile pigs is comparable to children, pigs may be a potential animal model to investigate the impact and mechanisms of ARC on drug pharmacokinetics (PK) in children.2In this pilot study, the contribution of intravenous (IV) fluid administration on the development of ARC was investigated in piglets.MethodsEight seven-week-old pigs underwent an experiment without fluid therapy and two consecutive fluid treatments as CRI of a 0.9% NaCl solution (3 mL/kg/h and 6 mL/kg/h) over 36 hours, each time combined with IV administration of a cocktail of renal markers after 4 and 24 h of fluid administration. This cocktail consisted of iohexol (64.7 mg/kg body weight (BW), Omnipaque 300®, marker for GFR) and para-aminohippuric acid (10 mg/kg BW, marker for effective renal plasma flow). To assess the impact of ARC on the PK of antimicrobials, amikacin (7,5 mg/kg BW, Amukin®) was administered after 24 h of fluid therapy. PK modelling was performed with Phoenix® WinNonlin®.ResultsGenerally, an increase in GFR was observed after fluid administration when compared to the GFR values observed without fluid administration. 4 and 2 out of 7 pigs demonstrated ARC after 4 h of a CRI at 3 mL/kg/h and 6 mL/kg/h, respectively. 4 out of 7 pigs displayed ARC after 24 h of a CRI at 3 mL/kg/h and 6 mL/kg/h. Similar results were obtained for amikacin clearance.ConclusionAn important effect of fluid therapy on the development of ARC was observed in juvenile pigs. Further research is necessary to confirm this results in critically ill children.ReferencesDhont E, et al. Augmented renal clearance in pediatric intensive care: are we undertreating our sickest patients? Pediatric Nephrology 2018.Gasthuys E, et al. Postnatal Maturation of the Glomerular Filtration Rate in Conventional Growing Piglets As Potential Juvenile Animal Model for Preclinical Pharmaceutical Research. Frontiers in Pharmacology 2017;8.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).

BackgroundAccurate assessment of renal function is crucial in intensive care to guide therapy. Both acute kidney injury and augmented renal clearance (ARC) may compromise outcome. Common formulas to estimate glomerular filtration rate (GFR) are unreliable in critically ill adults.1 A comparison of a gold standard technique to assess GFR with these formula-based estimations has never been reported in pediatric intensive care (PICU) patients. Our aim was to evaluate the feasibility of measuring plasma iohexol clearance (CLIOHEX) for GFR assessment in critically ill children and to compare CLIOHEX with estimated GFR using the modified Schwartz formula (eGFRSchwartz).MethodsA prospective, interventional study was conducted at the PICU of the Ghent University Hospital, Belgium. Critically ill children without chronic kidney disease were included. After injection of a weight-dependent bolus of iohexol, serial blood samples (n=6) were taken over a 6-hours interval. CLIOHEX was compared to eGFRSchwartz. Correlation between both methods was assessed by a Pearson´s correlation coefficient (r).Bland-Altman plots were evaluated to assess bias and limits of agreement (LOA). ARC was defined as a GFR exceeding normal values for age plus two standard deviations.Results40 patients, median age 16 months (range 15 days -13,6 years), 72,5% males, were included. No adverse effects related to iohexol were observed. Median CLIOHEX was 121 ml/min/1.73m2 (range: 43–221 ml/min/1.73m2). ARC was present in 20 patients based on CLIOHEX. Median eGFRSchwartz was 81 ml/min/1.73m2 (range: 31–131 ml/min/1.73m2). Only 1 patient was identified with ARC by eGFRSchwartz. eGFRSchwartz was systematically lower than CLIOHEX. There was a good correlation between CLIOHEX and eGFRSchwartz (r = 0,69; p< 0,01). Bias was 34 ml/min/1.73m2 with LOA (-24,5; 93 ml/min/1.73m2)ConclusionCLIOHEX was safely used to measure true GFR in critically ill children. eGFRSchwartz systematically underestimates GFR, especially in patients with ARC and seems not reliable in this patient population.ReferenceBaptista JP, Neves M, Rodrigues L, Teixeira L, Pinho J, Pimentel J ( 2014) Accuracy of the estimation of glomerular filtration rate within a population of critically ill patients. J Nephrol. 27:403–410.Disclosure(s)Nothing to disclose

BackgroundOver the years pigs were promoted as potential animal model for humans due to their high degree of anatomical and physiological similarities with humans. Gasthuys et al. demonstrated that the maturation of the kidney function in terms of the glomerular filtration rate (GFR) in growing pigs was comparable to humans, but no data are currently available on renal plasma flow, renal tubular secretion and reabsorption.1 The aim of this pilot study was to unravel the contribution of distinct renal elimination processes in juvenile pigs and to compare with reported human values.MethodsEight seven-week-old pigs were intravenously administered a single bolus of a cocktail of following renal markers: iohexol (64.7 mg/kg body weight (BW), GFR), para-aminohippuric acid (PAH, 10 mg/kg BW, effective renal plasma flow (ERPF) and anion secretion), pindolol (0.05 mg/kg BW, cation secretion) and fluconazole (0.5 mg/kg, tubular reabsorption). Plasma and urinary concentrations were determined for PAH, pindolol and fluconazole at several time points. Only plasma concentrations were assessed for iohexol. PK modelling was performed with Phoenix® WinNonlin®.ResultsThe clearance of iohexol was 97.9 ± 16.1 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 9.5 ± 2.1 ml/min/kg. These GFR and ERPF values are approximately a factor 1.3 higher than the values observed in humans, namely 63.5–75.0 mL/min/m² and 6.5 ± 2.0 mL/min/kg.2,3 The net tubular secretion of PAH was 5.4 ± 1.8 mL/min/kg, which was comparable with the values obtained in humans (5.0 ± 1.8 mL/min/kg).3 Results for cation secretion and tubular reabsorption are not yet available (to be presented at the congress).ConclusionThe net tubular secretion of PAH was comparable between the juvenile pigs and humans. The GFR and ERPF were generally a factor 1.3 higher in juvenile pigs compared to humans.ReferencesGasthuys E., et al., Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. Frontiers in Pharmacology 2017. 8.Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatric Nephrology 2007;22(11):1839–1848.Gross AS, et al., Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol. British Journal of Clinical Pharmacology 2001. 51(6):547–555.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).

Background Transition between different healthcare settings is a risk factor for medication discrepancies in the patient’s medication list. A large number of discrepancies has the potential to cause adverse drug events. Purpose Obtaining a complete medication list of a patient is very important to avoid unintentional medication discrepancies and medication related problems at admission. We aimed to evaluate the added value of a structured medication review in the emergency department by a pharmacy technician. Material and methods Well trained pharmacy technicians performed a medication review of patients admitted to the emergency department by using a structured form and different sources (patient, family, medication list, family doctor, etc). The physician acquired medication list was compared with that acquired by the technician to identify unintentional discrepancies (any difference between the two medication lists). The clinical impact was evaluated by a multidisciplinary team of pharmacists and pharmacologists. Results From February to April 2016, 279 (74.9%) medication discrepancies were identified in 113 medication lists. The most common discrepancies were omission of a drug (43.7%), omission of frequency (17.2%) and omission of dose (14.7%). Drugs belonging to the class of analgesics (21.1%) and obstructive airway disease (18%) were associated with the highest discrepancy rates. There was a positive association between the number of discrepancies and the number of drugs (p=0.002) and information sources (p=0.026) and the time needed to perform the reconciliation (p=0.001). 6.5% were evaluated as having a potentially very significant impact on the patient’s health; 30.6% were evaluated as having the potential to cause moderate clinical impact and 2.2% as potentially having a minor or no impact. Conclusion This study provides evidence that structured medication review is useful to obtain a complete medication history, to avoid medication related problems and to guarantee the patient’s safety. References and/or acknowledgements Mueller SK, et al. Arch Intern Med2012;172:1057–69. No conflict of interest

Defibrillation within the first minutes after sudden cardiac arrest can save many quality-adjusted life years. Yet, despite enormous investments, 'healthcare' is still unable to provide this for the majority of patients. Emergency Medical Services often have a too long mean response time and many issues surround Public Access Defibrillation programs. In this article we argument that AED-equipped drones could be the 'magic bullet'. They are easily deployed and fast, and have a relatively low operational cost. As such they could rapidly bring an AED next to the victim, irrespective of most geographical circumstances, give visual feedback and situational awareness to the EMS dispatcher and thus assist a bystander to provide better CPR. Although there are many real-life barriers to actual deployment, we argument these might all get solved once we have solved the described technological issues.

A multimethod approach using petrography and strontium (Sr) isotopic analysis was applied to determine the geological source of 17 marble artefacts from the Roman town of Ammaia (Portugal). All samples are calcitic, with dolomite, quartz and muscovite as accessory minerals. The marbles are characteristically medium-grained with a maximum grain size (MGS) between 0.98 mm and 1.82 mm, have a heteroblastic texture, and have curved to embayed calcite grain boundaries. 87Sr/86Sr values of marble leachates range from 0.708488 to 0.708639. Comparison with Hispanic and Mediterranean marbles suggests the Estremoz Anticline as the most likely source for the Ammaia marble, especially for architectural marble. This hypothesis is supported by the geographical proximity of the Estremoz marble district and the long and expensive overland transport required for other marbles to reach Ammaia.

Healthcare-associated pneumonia (HCAP) is considered to represent a category of disease distinct from community-acquired pneumonia (CAP). We describe the incidence and characteristics of HCAP compared with CAP in patients hospitalised through the emergency department (ED). Pneumonia diagnosed at the ED of Ghent University Hospital from 1 November 2006 to 31 October 2007 was retrospectively categorised as CAP or HCAP according to the definition of the American Thoracic Society/Infectious Diseases Society of America. We categorised 287 episodes of pneumonia, diagnosed in 269 patients, as CAP [159 (55%)] or HCAP [128 (45%)]. Patients with HCAP were older [75 years (range: 64-83) vs 68 (41-78); P < 0.001], had more comorbidity, and had more severe pneumonia [CURB-65: 2 (1-3) vs 1 (0-2); P < 0.001] in comparison to patients with CAP. Patients with HCAP had more frequently an unfavourable clinical course (27% vs 15%; P < 0.01) and a longer hospital stay (12 days vs 9 days; P

When sampling white marble for INAA, using a diamond core drill and circular saw the inevitable contamination can be removed by etching the samples with HNO3 (1N). Samples are etched for five minutes, first immediately after extraction and a second time after irradiation. For cooling the drill and saw, distilled water must be used whereas pro analysi acid is shown to be sufficiently pure to prepare the etchant with.

Good quality basic life support (BLS) results in better survival. BLS is a core competence of nurses but despite regular refresher training, the quality of BLS is often poor and the reasons for this are not well known. We therefore investigated the relation between BLS quality and some of its potential determinants.During a BLS refresher course, 296 nurses from non-critical care wards completed a questionnaire including demographic data and a "self-confidence" score. Subsequently, they performed a BLS test on a manikin connected to a PC using Skillreporting System software (Laerdal, Norway). The following variables were recorded: number of ventilations/min, tidal volume, number of compressions/min, compression rate, compression depth, "good ventilation" (nor=4 min(-1) and tidal volume=700-1000 ml) and "good compression" (nor=40 min(-1) and rate=80-120 min(-1) and compression depth=40-50mm). To detect independent determinants of BLS quality, associations between the demographic data and the objective variables of BLS quality were examined.Forty-three percent of the nurses rated their confidence as good or very good. Male gender was associated with good compression (P0.001). Greater self-confidence was also associated with good ventilation (P0.03) and with good compression (P0.001). A short time since last BLS training was associated with a higher number of ventilations/min (P=0.01). A short time since last experience of CPR was associated with a higher number of compressions (P0.01).Male gender, greater self-confidence, recent BLS training and recent CPR were associated with better quality of BLS.

Antecedentes La continuidad de la atencion (CC) es el grado en que el paciente experimenta la atencion con el tiempo como coherente y vinculada. Se identifican tres tipos de CC: relacional, informativo y gerencial. El objetivo es determinar el grado de continuidad de la atencion entre la atencion primaria (PC) y la atencion secundaria (SC) e identificar los factores asociados en Brasil y Colombia, paises con diferentes sistemas de salud. Metodos Estudio transversal mediante una encuesta de poblacion en Brasil (Pernambuco, n = 465) y Colombia (Bogota, n = 609) en 2011. Se analizaron los usuarios de los servicios de salud de los sistemas de salud publica de cada pais. Variables de resultado: indices sinteticos en CC relacional, informativo y gerencial. Variables explicativas: caracteristicas sociodemograficas y salud. Se realizaron analisis descriptivos y modelos de regresion logistica multivariante. Resultados El CC relacional fue mayor en Brasil que en Colombia tanto para los medicos de PC (82.2 y 72.9%, respectivamente) como para los medicos de SC (82.4 y 70.1%, respectivamente), pero la percepcion de una buena transferencia de informacion (CC informativo) es menor (56.3 y 67.6%, respectivamente). No se encontraron diferencias en la percepcion de consistencia de la atencion (CC gerencial) (alrededor del 70%). Entre los factores asociados con CC, se destacan los siguientes: en Brasil, la edad (ancianos) y el area (Caruaru, ciudad remota) se asociaron con cualquier tipo de CC. En ambos paises, la mala salud autoevaluada se asocio con niveles mas bajos de CC relacional y en Colombia, tambien, con el control clinico CC. Ademas, en Colombia, Conclusiones El nivel de continuidad relacional y gerencial percibida es alto, y de continuidad informativa, baja. Los factores asociados con la percepcion de la continuidad de la atencion difieren segun el pais y el tipo de continuidad de la atencion. Mensajes clave Es el primer intento de evaluar los tres tipos de continuidad de la atencion en areas de Colombia y Brasil. La comprension de los factores asociados con la continuidad de la atencion revelara que aspectos del sistema de salud publica podrian mejorarse.

"Introduccion Aunque la fragmentacion en la provision de atencion medica se considera un obstaculo importante para una atencion efectiva, la evidencia sobre las mejores practicas en la coordinacion de la atencion en America Latina es escasa. El objetivo del proyecto Equity-LA financiado por el 7PM es evaluar la efectividad de diferentes estrategias de integracion de la atencion para mejorar la coordinacion entre los niveles de atencion y la calidad de la atencion relacionada en seis sistemas de atencion medica: Argentina, Brasil, Chile, Colombia, Mexico y Uruguay. Metodos y analisis: Un estudio cuasi experimental controlado antes y despues que toma un enfoque de investigacion de accion participativa. En cada pais, se seleccionaron dos redes sanitarias comparables (intervencion y control). El estudio consta de cuatro fases: 1) Estudio de linea de base para establecer el desempeno de la red en la coordinacion y continuidad de la atencion, utilizando a) metodos cualitativos: entrevistas semiestructuradas y grupos focales de administradores de salud, profesionales y usuarios; yb) metodos cuantitativos: dos encuestas por cuestionario con muestras de 173 medicos de atencion primaria y secundaria y 392 usuarios con afecciones cronicas por red; tamano de muestra calculado para detectar una diferencia de proporcion de 15% y 10%, antes y despues de la intervencion (? = 0.05; ? = 0.2 en una prueba de dos lados); 2) Seleccion participativa ascendente, diseno e implementacion de estrategias de atencion compartida, un proceso dirigido por el comite directivo local; 3) Evaluacion de la efectividad de las intervenciones que aplican el mismo diseno que en el estudio de linea de base y los factores asociados; 4) Analisis comparativo entre paises. Resultados y relevancia El proyecto generara evidencia para informar la formulacion de politicas sobre las mejores practicas de integracion entre la atencion primaria y secundaria en diferentes tipos de sistemas de salud en America Latina, con especial referencia a las enfermedades cronicas, y sobre el efecto de los nuevos enfoques organizacionales en la calidad de la atencion, en diferentes contextos de asistencia sanitaria tambien relevantes para los sistemas sanitarios europeos. Mensajes clave Existe poca evidencia sobre las mejores practicas en coordinacion de la atencion en America Latina Los resultados sobre la coordinacion de la atencion pueden depender del factor contextual y del proceso. The Author 2015. Publicado por Oxford University Press en nombre de la Asociacion Europea de Salud Publica. Todos los derechos reservados."

Alcohol abuse is a major health concern. The aim of this retrospective study was to analyse the alcohol-related emergency department (ED) admissions among adolescents in all hospitals of distinct areas during a 1-year period. In each hospital, all ED patients with a blood alcohol concentration (BAC) of at least 0.5 g/l were surveyed in a standardised way. Of the 3918 included patients, only 146 (3.7%) were

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization ( FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.

This review addresses the pharmacotherapy of antidepressants in the elderly. We performed a search based on Medline and the Cochrane Library. In addition to a meta-analysis of 17 randomised controlled studies, 36 randomised controlled trials of patients over the age of 60 published between 1980 and 2005 in English met the selection criteria and were included. Existing evidence suggests that no one class of antidepressant drugs has been found to be more effective than another in the treatment of depression in the elderly. Although newer antidepressants are not more effective than older ones, they are better tolerated and are safe especially in overdose. The adverse effect data suggest modest superiority of selective serotonin reuptake inhibitors over tricyclic antidepressants. The evidence available indicates that antidepressant treatment of four weeks has a beneficial effect compared to placebo. As to prevention of relapse and recurrence, antidepressants should be continued for at least six months after good initial response. In patients with high risk of relapse, treatment should be continued for at least two years. Long-term efficacy has been shown for dosulepin, nortriptyline and citalopram. In patients with dementia with persistent and significant symptoms antidepressant treatment may be indicated. At present, clomipramine, citalopram and sertraline have been reported as being superior to placebo. There is a paucity of data on the use of antidepressants in very elderly individuals, patients with significant comorbidity and patients with dementia. More data on the effect of antidepressants in the elderly, especially in the over 80-age group are needed.

New petrographical and geochemical evidence of tourmalinite pebbles from two Lower and three Middle Devonian formations from Belgium is presented. Petrography, REE, transition metal and microprobe data of the studied rocks suggest it are (meta)sediment-derived tourmalinites formed by boron metasomatism (and hydrothermal brecciation) in an intrusive setting. Tourmaline mineralizations within eastern Avalonia are known in south-east Ireland, the English Lake District and East Anglia. Based on previously suggested relations between Early Palaeozoic igneous activity in last two mentioned regions and the Brabant Massif, it is presumed that the Brabant Massif also underwent granite-related tourmalinization and that this was the source of the studied pebbles. Petrologie differences between pebbles found in Middle Devonian formations and pebbles from Lower Devonian formations, suggest that fluid circulation occurred on a regional scale, possibly extending into the Stavelot massif.

OBJECTIVE: To compare the use of different healthcare levels, and its determinants, in two different health systems, the General System of Social Security in Health (GSSSH) and the Unified Health System (UHS) in municipalities in Colombia and Brazil. METHODS: A cross-sectional study was carried out, based on a population survey in two municipalities in Colombia (n=2163) and two in Brazil (n=2155). Outcome variables consisted of the use of primary care services, outpatient secondary care services, and emergency care in the previous 3 months. Explanatory variables were need and predisposing and enabling factors. Bivariate and multivariate logistic regression analyses were performed by healthcare level and country. RESULTS: The determinants of use differed by healthcare level and country: having a chronic disease was associated with a greater use of primary and outpatient secondary care in Colombia, and was also associated with the use of emergency care in Brazil. In Colombia, persons enrolled in the contributory scheme more frequently used the services of the GSSSH than persons enrolled with subsidized contributions in primary and outpatient secondary care and more than persons without insurance in any healthcare level. In Brazil, the low-income population and those without private insurance more frequently used the UHS at any level. In both countries, the use of primary care was increased when persons knew the healthcare center to which they were assigned and if they had a regular source of care. Knowledge of the referral hospital increased the use of outpatient secondary care and emergency care. CONCLUSIONS: In both countries, the influence of the determinants of use differed according to the level of care used, emphasizing the need to analyze healthcare use by disaggregating it by level of care.

"Introduccion: el cuestionario CCAENA evalua los tres tipos de continuidad de la atencion (relacional, informativa, gerencial) en todos los niveles de atencion desde la perspectiva del paciente. Habia sido validado para el contexto sanitario espanol. Objetivo: evaluar las propiedades psicometricas de la version abreviada de la escala CCAENA en el contexto colombiano y brasileno. Metodos: Estudio transversal mediante encuesta de poblacion en municipios de Colombia (n = 2,163) y Brasil (n = 2,167). Los datos se recopilaron en 2011 mediante un cuestionario que incluia 14 items de la escala CCAENA adaptados a ambos contextos (y traducidos). Se evaluaron la validez de constructo (analisis factorial exploratorio), la consistencia interna (alfa de Cronbach) y la multidimensionalidad (coeficientes de correlacion de Spearman). Resultados: Como en la version original, el analisis factorial mostro que los items se agruparon en tres factores: continuidad entre los niveles de atencion y la relacion entre el proveedor de atencion primaria y el proveedor de atencion secundaria. El alfa de Cronbach indico una buena consistencia interna (Colombia: 0.87, 0.91, 0.87; Brasil: 0.86, 0.89, 0.86). Los coeficientes de correlacion sugieren que los tres factores pueden interpretarse como escalas separadas (

Background: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN. Objectives: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident. Methods: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire. Results: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function. Discussion and conclusion: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population. (C) 2014. Published by Elsevier Ireland Ltd.

As drug instability and redistribution are factors known to affect the interpretation of post-mortem blood levels, we questioned whether post-mortem vitreous humour concentrations could be useful as predictors for the MDMA load at the time of death. In a first series of in vivo experiments using rabbits, 3,4-methylenedioxy-methamphetamine (MDMA) concentrations in plasma, blood and vitreous humour were studied as a function of time after intravenous (iv) administration of MDMA. Equilibration between the vascular compartment and vitreous humour was attained about 1 h after iv MDMA administration. In a second series of experiments, the post-mortem stability of MDMA in vitreous humour in relation to ambient temperature was investigated. Post-mortem MDMA concentrations in vitreous humour were closer to the ante-mortem blood levels when compared to cardiac blood samples. These preliminary investigations in the rabbit model indicate that measurements of vitreous humour concentrations could also be of interest for predicting the blood concentration at the time of death in humans.

Characteristic features of in situ diamonds can be used to retrace diamond formation during ultrahigh pressure (UHP) metamorphism of the Kokchetav Massif, Kazakhstan. These features include the nitrogen aggregation state in diamond, dissolution features observed on diamond surfaces, and the carbon and nitrogen isotopic composition of the diamonds. The minerals in which the diamonds are included provide additional information and support the view that at least some of the Kokchetav microdiamonds are the products of prograde or peak UHP metamorphism. The coexistence of diamond and graphite is evaluated within this framework.

The influence of hemorrhagic shock (removal of 30% of the blood volume) on the pharmacokinetics and the analgesic effect of morphine was investigated in conscious rats. Plasma concentrations of morphine after a bolus injection (5 mg/kg) are higher in the shock animals, which is attributed to a small decrease in clearance (-22%; P0.05) and a significant decrease in distribution volume (-33%; P0.05) of the drug. The areas under the plasma concentration-time curve of the metabolite morphine-3-glucuronide (M3G) are significantly higher (+237%; P0.01) in the shock rats, which is probably explained by a decreased distribution and renal excretion. The analgesic effect of morphine was evaluated using the tail-flick test during a continuous infusion (10 mg/kg/h) with measurement of the plasma concentrations of morphine and M3G. Data from these experiments show higher plasma concentrations of morphine (+33%; P0.05) and M3G (+66%; P0.05) during shock, and a significantly increased analgesic effect (+43%; P0.05). Our data suggest that the increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations.

Introduction Most studies examining inequities in access to health care in Colombia and Brazil consider the country as a whole, despite the existing internal inequalities; moreover, they do not distinguish between levels of the continuum of care. The aim is to analyze, in a comparative way, the degree of inequity in access to the different levels of the continuum of care in Colombia and Brazil. Methods Cross-sectional study by means of a questionnaire among people who have had at …

Purpose: The aim of this study was to prospectively evaluate drug interactions and adverse drug reactions (ADRs) in the older patients admitted to the emergency department (ED) and to characterize risk factors. Methods: In 80 patients aged 65 years and older medication history and ED drug administration were-analysed. Medical records were analysed for ADRs by an expert panel which also evaluated their avoidability and causality. An interaction program was used to search for potential drug interactions followed by assessment for clinical significance. Data were analysed using a logistic regression model. The significance level was set at alpha=0.05. Results: Eighty seven ADRs were identified in 37 patients; 18 were the result of an interaction (15 patients). Causality was assessed as definite (n = 1 ), probable (n = 62) and possible (n = 24). The reason for admission was definitely and probably related to an ADR in 6 and 18 patients respectively. Only 17 (20%) of the ADRs were assessed as unavoidable, while 23 (26%) and 47 (54%) were classified as definitely and possibly avoidable, respectively. ADRs were related with female gender (p = 0.023) and number of drugs (p = 0.004), but not with high age, (p = 0.151.). Clinically relevant interactions were related with older age (p = 0.032) and number of drugs (p = 0.003), but not with gender (p = 0.380). None of the interactions with ED initiated medications were considered unjustified. Conclusions: ADRs frequently occur in the older patients admitted to the ED and are an important cause of hospital admissions with a substantial contribution of adverse drug interactions.

Introduction: In many countries out of hours (OOH);,care is offered by different :health care services. General; practitioners (GP); tend to offer services in competition with emergency departments (ED). Patients behaviour : depends on a number of factors. In this study, we highlight the knowledge and ideas of patients concerning the co-payment system. Methods: We used a mixed methods design, combining quantitative-and qualitative research. During two week-ends in January 2005 all patients using the ED or the GP OOH service, were invited for an interview with a structured questionnaire. A-stratified random sample of patients participated; in a semi-structured interview. Both methods add-complementary data to answer the research-questions. Results:, Most Mentioned reasons-for seeking help at the ED are: accessibility (15.0%), proximity (64%) and; competence of the Staff (5.6%). Reasons for choosing the GP are; GP: is easy to find; Minor medical problem or anxiety and confidence in the GP The Odds of not knowing the. co-payment system are significantly higher in patients visiting the ED (OR 1:783; 95% CI: 1.493-2.129). Mostly GP users recognize the problem of ED overuse. They suggested especially to provide clear information about the tasks of the different:services and about the payment system, to reduce ED overuse, Conclusion and discussion; When intending to. shift from;ED to GP services for Minor medical problems, aiming at just one measure is no option. Information campaigns. aiming to :address the entire population; Can clarify the role of each player in Out-of-hours care.

Improving pain management in the ED might be attained by adequate teaching of medical students. We assessed the skills in pain treatment of ED physicians who teach the students.All physicians working in an ED who provide elective training to undergraduate medical students from the Ghent University were asked to complete a questionnaire consisting of vignette patient cases concerning acute pain management of abdominal colic pain, and non-traumatic abdominal pain.Thirty two physicians completed the cases. In the renal colic case 91% of the respondents proposed a NSAID as first line treatment. Butylhyoscine was still suggested by 18%. After initial failure of analgesia 31% administered a strong opioid. In biliary colic pain NSAIDs and butylhyoscine were proposed as first line analgesics by 59% and 31% respectively. In second line, butylhyoscine would be given by 22%. The patient case with right fossa abdominal pain would initially be treated with acetaminophen by 81%. Thirteen % of the respondents would not give further analgesia if the first line treatment was insufficient.Our results indicate that adherence by teachers to evidence based guidelines of acute pain management is insufficient. Therefore improving knowledge and skills in pain management of the teachers should receive more attention.

In order to investigate the influence of weathering on the isotopic composition of marble, surface crusts of naturally weathered marble samples from different ancient quarries were studied using stable isotope mass spectrometry. Isotopic analysis shows that there is a progressive increase in the abundance of the isotopes C-12 and O-16 from the interior marble to the weathered crust. The same technique was also used for the analysis of marble cores taken from authentic ancient artefacts. Analogous results were obtained. Although stable isotope analysis can be a valuable help for the authentication of ancient marble sculptures, it can not provide indisputable evidence, since patina layers on sculptures and weathered stones are very different, depending on the specific weathering conditions and conservation history of the artefact.

Primary granulocytic sarcoma is an uncommon entity that rarely presents in the breast. It is frequently misdiagnosed as carcinoma or lymphoma and a broad panel of immunohistochemical markers including epithelial and haematological markers are essential for an accurate diagnosis. We reviewed all the cases of granulocytic sarcoma reported in the English literature since 1970 and present a new case of granulocytic sarcoma of the breast. Systemic chemotherapy for acute myeloid leukemia (AML) appears to be superior to surgery or radiotherapy. Granulocytic sarcoma should be in the pathologic differential diagnosis of a breast mass.

The ECG analysis algorithm of automated external defibrillators (AEDs) shows reduced sensitivity and specificity in the presence of external artifacts. Therefore, ECG analyses are preceded by voice prompts. We investigated if advanced life support (ALS) providers follow these prompts, and the consequences if they do not.In a two-tiered EMS system all 510 ECG analyses from 135 resuscitation attempts with a Laerdal FR2 AED (applied by emergency medical technicians [EMTs] and subsequently used by ALS providers) were prospectively evaluated. The ALS data were compared with data before arrival of ALS providers (EMT data) using Mc Nemar test.In the presence of ALS providers, 286 ECG rhythm analyses were performed. In the 96 analyses with shockable rhythms, artifacts were detected in 35 (36%), leading to a wrongful no shock decision in 19 (20%). Corresponding EMT data were 67 analyses with shockable rhythms, with artifacts in 18 (27%; p0.001) but a wrongful no shock decision in only 3 (4%; p0.001). ALS providers also failed to deliver the AED shock in 7 of the 77 analyses with an appropriate shock decision (9%). This was never found in the EMT data. In the 190 analyses of a non-shockable rhythm in the presence of ALS providers, artifacts were detected in 120 (63%) leading to one spurious shock (0.5%). Corresponding EMT data were 157 analyses, with artifacts in 87 (55%; p=0.20) but no spurious shocks.External artifacts were frequently found, sometimes leading to important errors. Consequently, more training is needed, especially for ALS providers.

Alcohol and illicit drug abuse are major health care problems frequently leading to emergency department admission. The aims of this survey were (1) to determine for the Ghent University Hospital how frequently substance abuse contributed to emergency department admissions, (2) to describe the most important clinical features of these patients and (3) to determine how frequently these patients were referred to appropriate psychiatric services. All 1,941 patients attending the emergency department during the month of September 2003 were registered by the attending emergency department personnel. After exclusion of 8 cases, 1,933 patients were included: 198 (10%) with substance abuse leading to the emergency department admission (= INTOX group) and 1,735 (90%) in the NON-INTOX group. Males and the 21-50 years age group were overrepresented in the INTOX group. Patients with substance abuse were also overrepresented during the night, but not during the weekend. Among the patients from the INTOX group the most frequent reason for the emergency department visit was a psychiatric problem (102/198; 51%). Traumatic lesions related to a fight (n= 19), to a traffic accident (n= 17) and to leisure time activities (n=30) were also frequent. In most patients, only alcohol was abused (144/198; 73%), most frequently chronically (102/144; 71%). In 13% (26/198), there was only illicit drug use, and in 14% (28/198) alcohol abuse was combined with illicit drug use. Among the 54 patients with illicit drug use (with or without alcohol abuse) the most frequently reported drugs were cannabis (54%), cocaine (41%), amphetamines (39%) and opiates (39%). With regard to referral to appropriate psychosocial services it was striking that 53% (19/36) of trauma patients with chronic substance abuse were not offered that type of help. We conclude that abuse of alcohol--and to a much lesser degree illicit drugs--is a frequent cause of emergency department admissions. Our data may help to convince and/or reinforce health care policy makers, emergency department medical directors and the public that alcohol consumption (much more than illicit drugs) is responsible for avoidable morbidity and mortality, and that well-co-ordinated strategies against unhealthy alcohol use are urgently needed. In this respect, the importance of detection and referral of emergency department patients with unhealthy alcohol use should be stressed.

Diffuse large B-cell lymphoma (DLBCL) as defined by the World Health Organization (WHO) classification is clinically, morphologically and genetically a heterogeneous group of malignant proliferations of large lymphoid B cells. Over the last 6 years, several studies have been published improving our understanding of these lymphomas. These studies analyzed DLBCL by their gene expression profile, provided further information on some of the variants of DLBCL listed in the WHO classification and stressed the impact of the site of origin of these tumors. This review summarizes these recent data and explores their impact on the recognition of new clinicopathological lymphoma entities.