Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients.

BACKGROUND: Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600mut melanoma. High plasma concentration of D (PCD) is weakly associated with adverse events (AE). We investigated the relationship between PCD/T and tumour control or AE. METHODS: We analysed PCD/T in patients treated with D+T for metastatic melanoma. We collected data of tumour response (RECIST 1.1) and AE (CTCAE 4.0) blinded to PCD/T results. RESULTS: We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0ng/mL; interquartile range (IQR) [4-945]) and of PCT (median: 8.6ng/mL; IQR [5-39]) was observed. We found a weak relationship between PCD and progression-free survival, taking follow-up time into account (hazard ratio 0.991; 95%CI, 0.981 to 1.000; P=0.06). However, no difference was observed between mean PCD/T of progressing patients (n=21; 125±183ng/mL and 9.3±3.6ng/mL, respectively) and responders (complete, partial or stable response) (n=13; 159±225ng/mL, P=0.58 and 10.6±24.4ng/mL, P=0.29, respectively). No significant relationship was found between PCD/T and most common AEs (fever, lymphopenia, CPK increase, and hepatic cytolysis), body mass index, or age. Mean CPT (n=16) was significantly higher for female subjects (n=18; 11.5±4.8ng/mL) than for male subjects (8.8ng/mL±2.9, P=0.01), but no difference was observed between sex and CPD (P=0.32). CONCLUSION: Our study showed a weak relationship between PCD and progression-free survival, but no relationship between PCD/T and AE was found. Monitoring PCD and PCT alone is unlikely to be useful in assessing response to treatment.

Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

BACKGROUND: Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). OBJECTIVE: We sought to better describe adult IEN and understand the aetiology. METHODS: This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. RESULTS: IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. CONCLUSIONS: IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

AIM: Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA1c . This study explores the relationship between HbA1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. METHODS: Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA1c and FPG was assessed using a Kappa index. RESULTS: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. CONCLUSION: The relationship between HbA1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA1c to diagnose diabetes mellitus in this setting.

Characterisation of genetic structure of the Mayan population in Guatemala by autosomal STR analysis.

BACKGROUND: Currently, the Guatemalan population comprises genetically isolated groups due to geographic, linguistic and cultural factors. For example, Mayan groups within the Guatemala population have preserved their own language, culture and religion. These practices have limited genetic admixture and have maintained the genetic identity of Mayan populations. AIM: This study is designed to define the genetic structure of the Mayan-Guatemalan groups Kaqchiquel, K'iche', Mam and Q'eqchi' through autosomal short tandem repeat (STR) polymorphisms and to analyse the genetic relationships between them and with other Mayan groups. SUBJECTS AND METHODS: Fifteen STR polymorphisms were analysed in 200 unrelated donors belonging to the Kaqchiquel (n = 50), K'iche' (n = 50), Mam (n = 50) and Q'eqchi' (n = 50) groups living in Guatemala. Genetic distance, non-metric MDS and AMOVA were used to analyse the genetic relationships between population groups. RESULTS: Within the Mayan population, the STRs D18S51 and FGA were the most informative markers and TH01 was the least informative. AMOVA and genetic distance analyses showed that the Guatemalan-Native American populations are highly similar to Mayan populations living in Mexico. CONCLUSIONS: The Mayan populations from Guatemala and other Native American groups display high genetic homogeneity. Genetic relationships between these groups are more affected by cultural and linguistic factors than geographical and local flow. This study represents one of the first steps in understanding Mayan-Guatemalan populations, the associations between their sub-populations and differences in gene diversity with other populations. This article also demonstrates that the Mestizo population shares most of its ancestral genetic components with the Guatemala Mayan populations.

[Injection of Lipotransplants for Wound Healing Complications after Radiotherapy]. / Injektion von Bauchfett bei radiogenen Wundheilungsstörungen.

Wound healing complications in irradiated tissues represent a major clinical challenge. Fistula or even major vessel rupture may occur. The injection of adipose tissue derived stem cells seem to be a promising therapeutical strategy. The article describes the clinical case of a patient suffering from a pharyngo-cutaneous fistula after laryngectomy and radiotherapy. The patient was successfully treated by the injection of fat tissue.

Plasma vemurafenib concentrations in advanced BRAFV600mut melanoma patients: impact on tumour response and tolerance.

BACKGROUND: Vemurafenib improves survival in advanced BRAFV600(mut) melanoma patients, but tolerance is often poor and resistance frequently occurs, without predictive factor. Our aim was to investigate for the first time a relationship between plasma vemurafenib concentration (PVC) and efficacy or tolerance. METHODS: Plasma samples from unresectable metastatic BRAFV600(mut) melanoma patients treated with vemurafenib monotherapy were prospectively collected at each tumour response evaluation (RECIST 1.1) or when adverse event occurred (CTCAE 4.0). PVC was measured with liquid chromatography-tandem mass spectrometry. Herein, we report on PVC at steady state (≥14 days after vemurafenib introduction or dose modification). Samples collected after first melanoma progression were excluded from the response analysis. All samples were analysed in the tolerance analysis. We kept the closest collected sample from the onset of each adverse effect or the one with the highest PVC in the absence of this adverse effect. Comparisons of means (Student's t-tests and Wilcoxon rank sum tests) and of frequencies (χ(2) tests) were carried out. A logistic regression analysis identified predictors of progression. RESULTS: We included 105 plasma samples in 23 patients (10M/13F). Initial vemurafenib dose was 960 mg b.i.d., reduced by 25% (8 patients) or 50% (2 patients) for intolerance in 10 patients (44%). PVC displayed high inter-individual variability (13.0-109.8 µg/ml, median 54.0). Mean PVC was lower at time of first progression (38.8 ± 19.7 µg/ml) than mean PVC found when tumour was stable or in partial or complete response (56.4 ± 21.0 µg/ml, P = 0.013, 21 patients). Logistic regression revealed that having a low PVC (P = 0.01) or brain metastasis (P = 0.01) were both significantly and independently associated with tumour progression. High PVC was not statistically significantly associated with the occurrence of adverse effects. CONCLUSION: PVC at steady state is highly variable and low PVC was associated with tumour progression, suggesting a new path to melanoma resistance to vemurafenib.

Aerobic fitness and performance in elite female futsal players.

Despite its growing popularity, few studies have investigated specific physiological demands for elite female futsal. The aim of this study was to determine aerobic fitness in elite female futsal players using laboratory and field testing. Fourteen female futsal players from the Venezuelan National team (age =21.2±4.0 years; body mass =58.6±5.6 kg; height =161±5.0 cm) performed a progressive maximal treadmill test under laboratory conditions. Players also performed a progressive intermittent futsal-specific field test for endurance, the Futsal Intermittent Endurance Test (FIET), until volitional fatigue. Outcome variables were exercise heart rate (HR), VO2, post-exercise blood lactate concentrations ([La]b) and running speeds (km · h-1). During the treadmill test, VO2max, maximal aerobic speed (MAS), HR and peak [La]b were 45.3±5.6 ml · kg-1 · min-1, 12.5±1.77 km · h-1, 197±8 beats · min-1 and 11.3±1.4 mmol · l-1, respectively. The FIET total distance, peak running velocity, peak HR and [La]b were 1125.0±121.0 m, 15.2±0.5 km · h-1, 199±8 beats · min-1 and 12.5±2.2 mmol · l-1, respectively. The FIET distance and peak speed were strongly associated (r= 0.85-87, p < 0.0001) with VO2max and MAS, respectively. Peak HR and [La]b were not significantly different between tests. Elite female futsal players possess moderate aerobic fitness. Furthermore, the FIET can be considered as a valid field test to determine aerobic fitness in elite level female futsal players.

Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Interest in antifibrinolytic tranexamic acid (TA) has grown since the widespread removal of aprotinin, but its dosing during cardiac surgery is still debated. The objectives of this study were to investigate the population pharmacokinetics (PK) of TA given with either low- or high-dose continuous infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass (CPB). METHODS: Patients were randomized to receive either low-dose (10 mg kg(-1) followed by an infusion of 1 mg kg(-1) h(-1) throughout the operation, and 1 mg kg(-1) into the CPB) or high-dose (30 mg kg(-1), then 16 mg kg(-1) h(-1), and 2 mg kg(-1) into the CPB) TA. Serum TA concentrations were measured in 61 patients and the data were modelled using Monolix. RESULTS: TA concentrations were 28-55 µg ml(-1) in the low-dose group and 114-209 µg ml(-1) in the high-dose group throughout surgery. TA PK was best described by a two-compartment open model. The main covariate effect was bodyweight, whereas the CPB did not influence the PK. Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h(-1) for clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h(-1) for the diffusional clearance, and the peripheral volume of distribution was 10.8 litre. CONCLUSIONS: The PK of TA was satisfactorily described by an open two-compartmental model, which was used to propose a dosing scheme suitable for obtaining and maintaining the desired plasma concentration in a stable and narrow range in cardiac surgery patients.

Seasonal changes in physical performance and heart rate variability in high level futsal players.

The aim of this study was to determine the changes in physical performance and resting heart rate variability (HRV) in professional futsal players during the pre-season and in-season training periods. 11 athletes took part in the study (age=24.3±2.9 years; height=176.3±5.2 cm; weight=76.1±6.3 kg), and performed a repeated-sprint ability (RSA) test [6×40 m (20+20 m with a 180° change of direction) sprints separated by 20 s of passive recovery] and Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1) at 3 different moments (M1=beginning of pre-season; M2=end of pre-season; M3=mid in-season). The HRV indices were assessed at the same moments. After the short pre-season (3-week), mean RSA time (RSAmean) (M1=7.43±0.2 s; M2=7.24±0.2 s; P=0.003), decrement in RSA performance (RSAdecrement) (M1=6.7±0.3%; M2=5.0±0.9%; P=0.001), and Yo-Yo IR1 distance (M1=1.244±298 m; M2=1.491±396 m; P=0.002) were significantly improved (P<0.05). During the in-season (i. e., M3), performance in Yo-Yo IR1 and RSAmean were maintained. In contrast, RSAbest (M2=6.89±0.2 to M3=6.69±0.3; P=0.001) was improved and RSAdecrement (M2=5.0±0.9% to M3=6.6±0.9%; P=0.001) was impaired. At M2, there was an increase in HRV vagal-related indices compared with M1 that was maintained at M3. In conclusion, after a short pre-season, futsal players improved their RSA and Yo-Yo IR1 performance with concomitant improvements in HRV. These indices were maintained during the in-season period while RSAbest was improved and RSAdecrement impaired. Frequent monitoring of these performances and HRV indices may assist with identification of individual training adaptations and/or early signs of maladaption.

First Report of Powdery Mildew (Pseudoidium anacardii) of Mango Trees in Sinaloa, Mexico.

Powdery mildew of mango is an important disease in Mexico's northern Sinaloa state. Identification of the causal fungal agent has been hindered by the absence of information regarding its teleomorph, as well as a detailed morphometric analysis of the anamorph and molecular characterization. The first symptoms of the disease appear in mango inflorescences of early February, and it subsequently affects young fruits. The disease progresses during March and early April, causing significant fruit abortion and a scabby appearance in a high percentage of fruits that remain attached to the trees. We observed the disease on inflorescences but not in leaves during our sampling period. Powdery mildew specimens were collected during 2011 and 2012 and included Kent and Keith varieties from commercial orchards, and creole materials from backyards of private residences in the Ahome and Fuerte Counties of northern Sinaloa, Mexico. Symptomatic inflorescences were analyzed morphologically. Conidiophores and conidia were prepared by touching the whitish lesions with clear adhesive tape, which was then placed over microscope slides with a drop of distilled water and observed under a compound microscope. The anamorph structures of the pathogen were measured. The mycelium was septate and ramified on the surface of the host, forming a dense coat of branching hyphae. The mycelium had a diameter of 2.5 to 8.7 µm; conidiophores (Pseudoidium type) emerged from the superficial mycelium, were unbranched, and consisted of 1 to 3 cells with conidia forming singly from the apex. The length of the conidiophores varied from 30.0 to 77.5 µm; the foot cell of the conidiophores was straight, 10.0 to 47.5 µm long and with a diameter of 5.0 to 15.5 µm across its midpoint. Conidia without fibrosin bodies were borne singly, and were ellipsoid/ovoid, 22.5 to 46.2 µm long and 15.0 to 27.5 µm wide. Eighty percent of the germ tubes were forked (lobed); the rest were simple, emerged from the end, and were occasionally on the side of the conidia. Germ tubes ranged from 2.0 to 7.2 µm at the midpoint. The surface of the conidia appeared smooth under the scanning electron microscope, and elliptical conidia appeared constricted at their ends; this, however, was not observed in the ovoid conidia. In both cases, the terminal end of the conidia was smooth. The teleomorph was not found. Molecular and phylogenetic analysis of the ITS rDNA (2) region showed that samples are closely related to specimens of Pseudoidium anacardii (1) (teleomorph: Erysiphe quercicola [4]) collected from mango trees in diverse countries. Measurements of somatic and asexual structures are in agreement with descriptions of P. anachardii (formerly known as Oidium mangiferae) from India (3). The nucleotide sequences derived from this research were deposited in GenBank (Accession Nos. JX893951 to JX893957). To our knowledge, this is the first report of P. anacardii associated to mango inflorescences in Sinaloa, Mexico. Due to the economic importance of powdery mildew of mango trees in Sinaloa, future research directions should focus on finding the teleomorph of the fungus to support its identity. References: (1) U. Braun and R. T. A. Cook CBS Biodiversity Series No. 11, 2012. (2) S. Limkaisang et al. Mycoscience 47:327, 2006. (3) O. Prakash and K. C. Srivastava. Mango diseases and their management. A World Review Today and Tomorrow Publishers. New Delhi, India, 1987. (4) S. Takamatsu et al. Mycol. Res. 111:809, 2007.

Retention of Escherichia coli, Giardia lamblia cysts and Ascaris lumbricoides eggs in agricultural soils irrigated by untreated wastewater.

In central Mexico, agricultural irrigation reusing Mexico City's municipal wastewater has been occurring for the last century, resulting in the recharge of the local aquifer. However, groundwater of this zone is of good quality, indicating that the microorganisms contained in wastewater are retained by soil after infiltration. This study aims to assess the capacity of three agricultural soils to retain three microorganisms frequently found in wastewater, namely Escherichia coli (E. coli), Giardia lamblia (G. lamblia) cysts and Ascaris lumbricoides (A. lumbricoides) eggs, through batch sorption-desorption assays. The tested soils were: an organic-clayey soil (C-OM), a clayey soil (C-om) and a sandy soil (c-om). For the three soils, sorption equilibrium of E. coli was reached before 1 h, while for G. lamblia cysts and A. lumbricoides eggs, sorption equilibrium took 2.5 h. Sorption of E. coli was better described by the Freundlich model than by the Langmuir one. Higher retention of bacteria was observed in the C-om soil (KF = 4340) than in the C-OM and c-om ones (KF = 1821 and 0.01, respectively). Regarding G. lamblia cysts and A. lumbricoides eggs, data could not be fitted to the tested sorption models. For both organisms, retention was lower in the C-OM soil than in the C-om and c-om ones. In the desorption tests, a sudden liberation of E. coli from soils was observed, probably due to bacterial re-growth. Desorption of G. lamblia was higher in the sandy soil than in the clayey ones; desorption was not increased when a surfactant was applied to the soil, suggesting that hydrophobic interactions are not necessarily responsible for retention of the cysts onto the tested soils. For A. lumbricoides eggs, desorption using NaOCl solution suggested that retention was caused by interactions between the mineral fraction of the soil and the external walls of eggs. This study showed that the three target microorganisms are retained by the tested soils and that mineral domain of soil has an important role in such retention.

Validation of a short useful questionnaire in Spanish for the epidemiological screening of epilepsy in Spain. EPIBERIA Questionnaire.

INTRODUCTION: There is a major gap in knowledge about the epidemiology of epilepsy in Mediterranean countries. The EPIBERIA group was formed with the aim of promoting the conducting of epidemiological studies in this region in order to improve this situation. This paper deals with the validation of a brief questionnaire for screening patients with epilepsy in the general population. METHODS: We selected an English-language questionnaire previously validated by the Ottman group. It was translated, modified to suit the characteristics of the Spanish population, and administered to a sample of 200 patients (93 epileptics and 107 non-epileptic patient controls) sampled consecutively from 5 epilepsy units in different cities in Spain. Both groups were homogeneous in demographic variables and the control group was representative of the general population. RESULTS: We obtained a sensitivity of 100% and a specificity of 74.77% for the least rigorous correction model for the questionnaire, with a sensitivity of 94.62% and a specificity of 99.07% for the most stringent correction model. The PPV ranged from 7.48% for the first case to 69.49% in the second, assuming an epilepsy prevalence of 2%. CONCLUSIONS: The questionnaire EPIBERIA is a valid Spanish tool for epilepsy screening in the general population in Spain.

The duration of ketamine detection in hair after treatment cessation: Case study and review of the literature in forensic and clinical casework.

The disappearance of drug from hair does not occur immediately after abstinence because dormant hair may contribute to the positivity of freshly grown hair. The aim of this study was to assess ketamine disappearance from hair after treatment cessation and to review the literature data. A 22-year-old female received three intravenous doses of ketamine (171 mg) for major depression treatment. Seventeen weeks later, a 26 cm lock of hair was sampled, and ketamine was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) on seven segments: A (proximal, 0-2 cm), B (2-4 cm), C (4-6 cm, period of ketamine therapy), and D to G (4 × 5 cm). Ketamine concentration was 58 pg/mg in Segment C and remained detectable over 4 months after treatment cessation at 67 pg/mg in Segment B and 2 pg/mg in Segment A, representing a 97% drop from the initial concentration. Ketamine elimination half-life in hair was estimated at 0.88 month, implying that indetectable concentration should be expected 7 months after cessation. Axial diffusion was excluded as ketamine was not detected in Segments D-G. Given the low ketamine concentrations, norketamine was not detected. While no data on ketamine disappearance from hair have been published to date, previous studies have shown that discontinuation resulted in negative hair results after 3 months for heroin, 3-4 months for cocaine and tramadol, 6 months for amphetamine and methamphetamine, and 6-7 months for THC-COOH. This study provides useful findings for ketamine hair concentration interpretation, which should be validated by more consistent and comprehensive investigations.

Photoelectron Spectroscopy of Oppositely Charged Molecular Switches in the Aqueous Phase: Theory and Experiment.

XUV photoelectron spectroscopy (XPS) is a powerful method for investigating the electronic structures of molecules. However, the correct interpretation of results in the condensed phase requires theoretical models that account for solvation. Here we present experimental aqueous-phase XPS of two organic biomimetic molecular switches, NAIP and p-HDIOP. These switches are structurally similar, but have opposite charges and thus present a stringent benchmark for solvation models which need to reproduce the observed ΔeBE = 1.1 eV difference in electron binding energy compared to the 8 eV difference predicted in the gas phase. We present calculations using implicit and explicit solvent models. The latter employs the average solvent electrostatic configuration and free energy gradient (ASEC-FEG) approach. Both nonequilibrium polarizable continuum models and ASEC-FEG calculations give vertical binding energies in good agreement with the experiment for three different computational protocols. Counterions, explicitly accounted for in ASEC-FEG, contribute to the stabilization of molecular states and reduction of ΔeBE upon solvation.

Genetic identification of missing persons: DNA analysis of human remains and compromised samples.

Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers.

Drug-resistant epilepsy: current recommendations for diagnosis and treatment in Spain.

INTRODUCTION: Drug-resistant epilepsy (DRE) is a top-priority social health problem which requires early individual treatment due to its dramatic repercussions for the patient and society. DEVELOPMENT: The International League Against Epilepsy (ILAE) has recently defined DRE as that in which the seizures are not controlled after having correctly taken two appropriate and well tolerated anti-epileptic drugs, with lack of control being understood as the appearance of seizures within one year or in a period less than three times the inter-seizure interval before starting treatment. This International Society recommends a rapid and detailed assessment of all patients in an Epilepsy Unit. A Clinical Epilepsy Unit (CEU) is understood as a group of professionals who, acting in collaboration, have the diagnosis and treatment of the patient with epilepsy as their primary objective. CEUs in Spain may be stratified into different levels depending on the activity carried out in each of them. The specific epilepsy clinic is considered the fundamental type of CEU and includes the necessary figure of an expert in epilepsy. Prolonged video-monitoring is performed in medical CEUs. In medical-surgical CEUs epilepsy surgery with varying degrees of difficulty is also performed. CONCLUSIONS: All CEUs must cooperate with consensus protocols, and there must be a two-way flow between them. Stratification of CEUs increases efficacy and efficiency, due to there being a sufficient number of them to ensure easy access by all patients with epilepsy.

Consensus-recommended diagnostic and therapeutic guidelines for drug-resistant epilepsy in Spain (Consenso RATE-España).

OBJECTIVE: To ascertain the opinions of an Epilepsy Expert Group and prepare a consensus document on the definition of drug-resistant epilepsy (DRE) according to the International League Against Epilepsy (ILAE) and the different healthcare levels for the patient with epilepsy in Spain. MATERIAL AND METHODS: The study was conducted using the Delphi method, by means of successive rounds of questionnaires. A scientific committee prepared a preliminary document and fourteen associated questions, which were sent by e-mail to the panel of experts. They included items related to the concept of DRE, health care levels and the route between these levels for patients with DRE. RESULTS: A total of 41 experts answered the questionnaire. They agreed regarding the necessity and applicability of the DRE definition according to the ILAE, the need for an expert panel on epilepsy, specialist epilepsy clinics, and clinical epilepsy units stratified depending on the level of activities they carried out. There was moderate consensus on the resources and activity of the clinical units of reference and there was no consensus on the referral of patients who have suffered an epileptic seizure to an epilepsy clinic. CONCLUSIONS: The expert panel agreed with the definition of DRE according to the ILAE and on referring patients with DRE for a detailed study in an epilepsy clinic or epilepsy clinical unit. They highlighted the need for video-EEG monitoring in the study of patients with DRE and the need to propose other forms of treatment in selected patients.

[Improve of efficiency of patients management admitted in an Intermediate Respiratory Care Unit by means of an integrated delivery of health care]. / Mejora en la eficiencia del manejo del paciente ingresado en una unidad de cuidados respiratorios intermedios tras la introducción de un proceso asistencial integrado.

INTRODUCTION: Patients admitted to Intermediate Respiratory Care Units are common sharpeners. We describe their overall improvement by the introduction of an Integrated Care Process. METHODS: We conducted an observational descriptive study based on an Intermediate Respiratory Care Unit during 2015-2017. We considered 2 groups: those in-patients during 2016-2017, who took profit from the Integrated Care Process (group A), and those other ones admitted before 2015 when the Integrated Care Process didn't exist yet (group B). We collected sociodemographic variables, clinical ones, those related to care process and economic index. We described them according their type and distribution. RESULTS: The readmission rate within B was 23.65% vs 10.20% within A. These last ones had a mean length of hospital stay of 7.19 days (0.12-14.08), a rate reduction of face-to-face specialized consultations of 45.8% and 28.8% at Emergency Department admissions when compared to B. Prior to the introduction of the Integrated Care Process, 64.9% would have been admitted to the Intensive Care Unit (according to Global Diagnostics Group). We saved 735.1 days of stay at the Intensive Care Unit and therefore over 135,118.204 and 214,649 euros. CONCLUSION: The Integrated Care Process for severe respiratory patients allows a direct and safe relationship with them at home through the Primary Care Teams, so we can save readmissions at hospital, face-to-face consultations at the Emergency Departments and Specialized Consultations and we save money.