[Evaluation of factors associated with major hemorrhage in patients undergoing primary total hip arthroplasty]. / Evaluación de factores asociados a hemorragia mayor en pacientes sometidos a artroplastía total de cadera primaria.

INTRODUCTION: the use of blood transfusions leads to increased hospital costs and an increased risk of medical complications and death. Therefore, it is necessary to study the incidence of major bleeding events and the factors associated with these outcomes in patients undergoing primary total hip arthroplasty (THA). MATERIAL AND METHODS: observational, longitudinal and prospective study, carried out at the High Specialty Medical Unit of Traumatology and Orthopedics of Lomas Verdes of the Mexican Institute of Social Security, in the Joint Replacement Service, in the period from March 1, 2020 to July 1, 2020. RESULTS: the incidence of major bleeding in patients undergoing primary THA was 84.8%, when considering two criteria: a decrease in hemoglobin 2 g/dl and the need for transfusion 2 units of red blood cells. This figure increased to 87.1% when also including trans-surgical bleeding at its 75th percentile, equivalent to 500 ml. Transfusion of at least one unit of red blood cells during surgery was performed in 68% of patients. Trans-surgical bleeding reached a maximum of 1,900 ml, with a 75th percentile of 500 ml. Unlike other studies, in our institution, female gender did not prove to be a significant risk factor for major bleeding. CONCLUSION: it is advisable to analyze the procedures and particularities of THA surgery that may be associated with a lower risk of bleeding in older patients.

INTRODUCCIÓN: el uso de transfusiones sanguíneas conlleva aumentos en los costos hospitalarios y un mayor riesgo de complicaciones médicas y fallecimientos; por lo que es necesario el estudio de la incidencia de eventos de hemorragia mayor y de los factores que se asocien a estos desenlaces en los pacientes que se someten a una artroplastía total de cadera (ATC) primaria. MATERIAL Y MÉTODOS: estudio observacional, longitudinal y prospectivo, llevado a cabo en la Unidad Médica de Alta Especialidad de Traumatología y Ortopedia de Lomas Verdes del Instituto Mexicano del Seguro Social, en el Servicio de Reemplazo Articular, en el período comprendido entre el 01 Marzo 2020 al 01 Julio 2020. RESULTADOS: la incidencia de hemorragia mayor en pacientes sometidos a ATC primaria fue de 84.8%, al considerarse dos criterios: una disminución de hemoglobina 2 g/dl y la necesidad de transfusión 2 unidades de glóbulos rojos. Esta cifra aumentó a 87.1% al incluir también el sangrado transquirúrgico en su percentil 75, equivalente a 500 ml. La transfusión de al menos una unidad de glóbulos rojos durante la cirugía se realizó en 68% de los pacientes. El sangrado transquirúrgico alcanzó un máximo de 1,900 ml, con un percentil 75 de 500 ml. A diferencia de otros estudios, en nuestra institución, el género femenino no demostró ser un factor de riesgo significativo para la hemorragia mayor. CONCLUSIÓN: es aconsejable analizar los procedimientos y las particularidades de la cirugía de ATC que puedan estar asociados con un menor riesgo de hemorragia en los pacientes mayores.

Resident physician duty hours, resting times and European Working Time Directive compliance in Spain: a cross-sectional study.

BACKGROUND: There is a growing interest in understanding the impact of duty hours and resting times on training outcomes and the well-being of resident physicians. However, to this date no state-wide analysis exists in any European country. OBJECTIVES: Our aim is to describe the shift work scheduling and to detail the degree of compliance with the Spanish legislation and the European Working Time Directive (EWTD) of Spanish resident physicians, focusing on territorial and specialty distribution. MATERIAL AND METHODS: A descriptive cross-sectional analytical study was designed through an online survey adapted from the existing literature. RESULTS: Out of the 2035 surveyed resident physicians undergoing PGT in Spain, 80.49% exceeded the 48 h per week limit set by the EWTD and 13% of them did not rest after a 24-h on-call shift. The mean number of on-call shifts in the last 3 months was 15.03, with the highest mean reported in Asturias, La Rioja, and Extremadura. 51.6% of respondents had a day-off after a Saturday on-call shift. Significant differences are observed by region and type of specialty. CONCLUSION: Resident physicians in Spain greatly exceed the established 48 h/week EWTD limit. Likewise, non-compliance with labor regulations regarding mandatory rest after on-call duty and minimum weekly rest periods are observed.

B-esterase measurements and other blood related biomarkers in loggerhead sea turtles (Caretta caretta) as indicators of health status.

The loggerhead sea turtle (Caretta caretta) has been selected as sentinel species by the Marine Strategy Framework Directive (MSFD) descriptor 10 in relation to marine litter. In this, and other protected species, there is a need to develop conservative pollution biomarkers equally informative of chemical exposures to those traditionally carried out in metabolic organs, such as the liver. With this aim, plasma from turtles undergoing rehabilitation at the Fundació Oceanogràfic rescue centre (Arca del Mar) were selected and tested for B-esterase measurements. Hydrolysis rates of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterases (CEs) using four commercial substrates were undertaken on 191 plasma samples. Results indicated that acetylthiocholine was the most adequate substrate of cholinesterases and butyrate esters for CE measures. The correlation of these parameters with well-established blood biochemistry measurements was analysed. B-esterase measures in wild specimens were discussed in relation to age group, pathology on admission to the rescue centre and season; moreover, contrasts with long-term resident turtles were also made. Although this study provides baseline data on B-esterase measures in a large sample size for this species, more complementary information is still needed in terms of population genetics, chemical exposures, and in relation to other biochemical parameters before they can be confidently applied in wild specimens within the regulatory MSFD.

Bottlenose dolphins (Tursiops truncatus) aggressive behavior towards other cetacean species in the western Mediterranean.

Aggressive behavior of bottlenose dolphins (Tursiops truncatus) towards conspecifics is widely described, but they have also often been reported attacking and killing harbour porpoises (Phocoena phocoena) around the world. However, very few reports exist of aggressive interactions between bottlenose dolphins and other cetacean species. Here, we provide the first evidence that bottlenose dolphins in the western Mediterranean exhibit aggressive behavior towards both striped dolphins (Stenella coeruleoalba) and Risso's dolphins (Grampus griseus). Necropsies and visual examination of stranded striped (14) and Risso's (2) dolphins showed numerous lesions (external rake marks and different bone fractures or internal organ damage by blunt trauma). Indicatively, these lessons matched the inter-tooth distance and features of bottlenose dolphins. In all instances, these traumatic interactions were presumed to be the leading cause of the death. We discuss how habitat changes, dietary shifts, and/or human colonization of marine areas may be promoting these interactions.

[Vaccine against COVID-19]. / Vacuna frente al COVID-19.

The COVID-19 pandemic has produced a huge health, economic and psychological collapse in our society. Health workers have had to face one of the greatest challenges in history, trying to show the population how to deal with this disease. We have learned that vaccines are the great instrument for the fight against infectious diseases and a large number of them began to appear, not as a product of chance but as a product of the enormous progress experienced in recent years with vaccines against new infectious diseases, against other diseases such as Alzheimer's and especially against cancer. All this knowledge has been applied to this disease. Practitioners lamented the little information available to them when asked questions from patients. This document wanted to be a response to these concerns, with a scientific desire, with evidence that put aside unverified data and hoaxes. Faced with an avalanche of information, most of it without the appropriate "peer review" as indicated in the introduction, any publication becomes obsolete at the time of publication, and we opted for an "online" publication, with the incorporation of versions. This online publication has been published in the documents of Spanish Society of Chemotherapy, at https://seq.es/vacunacion-covid-19.

On-board study of gas embolism in marine turtles caught in bottom trawl fisheries in the Atlantic Ocean.

Decompression sickness (DCS) was first diagnosed in marine turtles in 2014. After capture in net fisheries, animals typically start showing clinical evidence of DCS hours after being hauled on-board, often dying if untreated. These turtles are normally immediately released without any understanding of subsequent clinical problems or outcome. The objectives of this study were to describe early occurrence and severity of gaseous embolism (GE) and DCS in marine turtles after incidental capture in trawl gear, and to provide estimates of on-board and post-release mortality. Twenty-eight marine turtles were examined on-board fishing vessels. All 20 turtles assessed by ultrasound and/or post-mortem examination developed GE, independent of season, depth and duration of trawl and ascent speed. Gas emboli were obvious by ultrasound within 15 minutes after surfacing and worsened over the course of 2 hours. Blood data were consistent with extreme lactic acidosis, reduced glomerular filtration, and stress. Twelve of 28 (43%) animals died on-board, and 3 of 15 (20%) active turtles released with satellite tags died within 6 days. This is the first empirically-based estimate of on-board and post-release mortality of bycaught marine turtles that has until now been unaccounted for in trawl fisheries not equipped with turtle excluder devices.

Efficacy of nintedanib and docetaxel in patients with advanced lung adenocarcinoma treated with first-line chemotherapy and second-line immunotherapy in the nintedanib NPU program.

PURPOSE: Both nintedanib/docetaxel and anti-PD-1/PD-L1 immunotherapies have demonstrated efficacy as second-line treatment of patients with advanced lung adenocarcinoma. This is the first report on the efficacy of the nintedanib/docetaxel combination following first-line platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. METHODS/PATIENTS: From May 2014 to December 2015, 390 patients in 108 Spanish centres enrolled in the nintedanib named patient use program. Inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. The objective was to evaluate the efficacy of the nintedanib/docetaxel combination in patients who also received immunotherapy. RESULTS: Eleven patients met the inclusion criteria; with a median age of 67 years. PD-L1 expression was positive in six patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (95% CI 1.9-4.6). Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) or nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (95% CI 0-6.1). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. Median PFS of nintedanib/docetaxel was 3.2 months (95% CI 1.9-4.5). Best response was partial response in four patients (36%), stable disease in five patients (46%), and progressive disease in two patients (18%), for an ORR of 36% and a DCR of 82%. CONCLUSION: Our experience suggests an encouraging efficacy of nintedanib/docetaxel in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy, reinforcing the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma.

Improvement of appropriate pharmacological prophylaxis in hospitalised cancer patients with a multiscreen e-alert system: a single-centre experience.

PURPOSE: Thromboprophylaxis use among medical inpatients, including cancer patients, is suboptimal. We aimed to evaluate the impact of a novel multiscreen version (v2.0) of an e-alert system for VTE prevention in hospitalised cancer medical patients compared to the original software. METHODS: Prospective study including 989 consecutive adult cancer patients with high-risk of VTE. Patients were followed-up 30 days post-discharge. Two periods were defined, according to the operative software. RESULTS: E-alert v2.0 was associated with an increase in the use of LMWH prophylaxis (65.5% vs. 72.0%); risk difference (95% CI) 0.064 (0.0043-0.12). Only 16% of patients in whom LMWH prophylaxis was not prescribed lacked a contraindication. No significant differences in the rates of VTE (2.9% vs. 3.2%) and major bleeding (2.7% vs. 4.0%) were observed. CONCLUSIONS: E-alert v2.0 further increased the use of appropriate thromboprophylaxis in hospitalised cancer patients, although was not associated with a reduction in VTE incidence.

Targeted DNA sequencing for assessing clonality in multiple lung tumors: A new approach to an old dilemma.

BACKGROUND: The differential diagnosis between multiple primary lung cancer (MPLC) and advanced lung cancer has traditionally relied on conventional radiology and pathology. However, the outcomes of traditional diagnostic workup are often limited, and staging is uncertain. Increasing evidence suggests that next-generation sequencing (NGS) techniques offer the possibility of comparing multiple tumors on a genomic level. OBJECTIVES: The objective of this study is to assess the clinical impact utility of targeted sequencing in patients presenting with multiple synchronous or metachronous lung tumors. MATERIALS AND METHODS: We describe the diagnostic workup conducted in a patient with three lung tumors, where we used a targeted 50-gene DNA sequencing panel (Ion AmpliSeq TM Cancer Hotspot Panel v2) to assess clonality and establish an accurate lung adenocarcinoma stage. Positive results were confirmed by pyrosequencing or Sanger sequencing. RESULTS: Three surgically resected lung tumors were submitted for targeted sequencing. The tumor from the upper right lobe was positive for a TP53 c.659A > G mutation and native for KRAS. The tumor from the upper left lobe was positive for TP53 c.725G > T and KRAS c.35G > T mutations. The tumor from the lower left lobe was positive for TP53 c.1024C > T and KRAS C.34G > T mutations. Results and reviewed literature in the field support the diagnosis of MPLC instead of a single advanced lung cancer. CONCLUSION: Targeted DNA sequencing significantly increases diagnostic accuracy in patients with multiple lung tumors. NGS panels should be available for patients presenting with multiple lung tumors.

Tromboelastometría como guía de administración de hemoderivados en cirugía cardiaca / Thromboelastometry as guidance for blood management in patients undergoing cardiac surgery

Objetivo. La tromboelastometría evalúa la coagulación analizando la viscoelasticidad de una muestra de sangre. Nuestro objetivo principal fue evaluar los resultados de su uso como guía de administración de hemoderivados en cirugía cardiaca y, secundariamente, las complicaciones postoperatorias y el tiempo de hospitalización en UCI. Material y método. Estudio analítico, de intervención, cuasiexperimental, comparativo, no aleatorizado, prospectivo, con un grupo control retrospectivo. Se incluyeron 80 pacientes reintervenidos de cualquier cirugía cardiaca, o cirugías por endocarditis o del arco aórtico. En 31 pacientes los hemoderivados intraoperatorios se administraron según pautas clínicas tradicionales (grupo A). Los 49 pacientes restantes recibieron hemoderivados siguiendo algoritmos basados en el análisis tromboelastométrico (grupo B). El objetivo principal fue la administración de hemoderivados y los objetivos secundarios fueron: estancia en UCI y complicaciones postoperatorias. Resultados. Hubo una importante disminución en la administración de plasma fresco congelado en el grupo B respecto al A (p<0,001), así como una disminución en la transfusión intraoperatoria de sangre: 3,9 concentrados de hematíes de media por paciente en el grupo A frente a 2,67 en el grupo B (p=0,125). Se incrementó la administración de fibrinógeno, con una p<0,019. Se encontró una menor tasa de complicaciones respiratorias (p=0,019) en el grupo B y una reducción significativa de las estancias mayores de 7 días en el grupo B respecto al A (p=0,031). Conclusiones. La tromboelastometría condujo a una importante disminución en la utilización de plasma fresco congelado, contribuyendo muy probablemente al descenso en la incidencia de complicaciones respiratorias y en la menor estancia en UCI (AU)

Objective. Thromboelastometry is a viscoelastometric method for haemostasis testing in a whole blood sample. The aim of this study was to assess the results of using thromboelastometry as guidance for blood management in cardiac surgery, postoperative adverse events and ICU stay. Material and method. Analytical and comparative non-randomised quasi-experimental prospective study with a retrospective control group. The inclusion criteria for the 80 patients were: patients undergoing cardiac surgery who had had prior cardiac surgery, endocarditis surgery or aortic arch surgery. Thirty-one patients were treated following routine transfusion practice during surgery (group A). The other 49 patients were treated with thromboelastometrically guided transfusion algorithms (group B). The main objective was blood products transfused, and postoperative adverse events and ICU stay were the secondary objectives. Results. Statistical analysis showed lower transfusion rates of fresh-frozen plasma in group B compared to group A (P<.001), as well as red blood cell transfusion during surgery with an average transfusion rate of 3.9 units in group A in comparison to 2.67 units in group B (P=.125). Moreover, fibrinogen infusion was increased in group B compared to group A (P=.019). In addition, a lower rate of respiratory adverse events was found in group B (P=.019). There was a significant decrease in ICU stays over 7 days in group B compared to group A (P=.031). Conclusions. Using thromboelastometry guidance for blood management led to a meaningful reduction of fresh frozen plasma transfusion during surgery. This probably resulted in a reduction in respiratory adverse events after surgery and length of ICU stay in our patients (AU)

Thromboelastometry as guidance for blood management in patients undergoing cardiac surgery. / Tromboelastometría como guía de administración de hemoderivados en cirugía cardiaca.

OBJECTIVE: Thromboelastometry is a viscoelastometric method for haemostasis testing in a whole blood sample. The aim of this study was to assess the results of using thromboelastometry as guidance for blood management in cardiac surgery, postoperative adverse events and ICU stay. MATERIAL AND METHOD: Analytical and comparative non-randomised quasi-experimental prospective study with a retrospective control group. The inclusion criteria for the 80 patients were: patients undergoing cardiac surgery who had had prior cardiac surgery, endocarditis surgery or aortic arch surgery. Thirty-one patients were treated following routine transfusion practice during surgery (group A). The other 49 patients were treated with thromboelastometrically guided transfusion algorithms (group B). The main objective was blood products transfused, and postoperative adverse events and ICU stay were the secondary objectives. RESULTS: Statistical analysis showed lower transfusion rates of fresh-frozen plasma in group B compared to group A (P<.001), as well as red blood cell transfusion during surgery with an average transfusion rate of 3.9 units in group A in comparison to 2.67 units in group B (P=.125). Moreover, fibrinogen infusion was increased in group B compared to group A (P=.019). In addition, a lower rate of respiratory adverse events was found in group B (P=.019). There was a significant decrease in ICU stays over 7 days in group B compared to group A (P=.031). CONCLUSIONS: Using thromboelastometry guidance for blood management led to a meaningful reduction of fresh frozen plasma transfusion during surgery. This probably resulted in a reduction in respiratory adverse events after surgery and length of ICU stay in our patients.

Perceived quality in a dementia unit: patients' caregivers as information providers. / Calidad percibida en una unidad de demencias: el portavoz del paciente como proveedor de información.

INTRODUCTION: Dementia units (DU) provide comprehensive and specialised care to patients with dementia. However, assessment in these units normally focuses on patient management. The aim of this study was to determine satisfaction of the caregivers of patients managed in a DU and how they rated DU care. METHODS: We created a self-administered questionnaire which was completed by 236 caregivers visiting the DU in 2015. The questionnaire included 6 dimensions (accessibility, organisation, professionalism, relationship with staff, information, and facilities); data were analysed using problem rates. RESULTS: A total of 53.4% caregivers completed the questionnaire; most were women, patients' spouses, or first-degree relatives. The overall problem rates was 15.0% (95% CI, 13.9-16.1), with sizeable differences between dimensions: from 0.1% (95% CI, 0.0-0.4) for 'relationship with staff' and 'professionalism' to 49.3% (95% CI, 45.4-53.2) for 'information'. Waiting times over 30minutes were perceived as excessive. Information problems were not directly related to patient management. Satisfaction was scored 8.29/10 (median 8; SD 1.45); 77.3% (95% CI, 69.8-74.8) of respondents were highly satisfied. Ninety-nine percent of the caregivers stated that they would recommend the DU. CONCLUSIONS: This questionnaire provides interesting data on care quality as perceived by patients' caregivers. Our results have allowed us to identify problems and implement corrective actions. Our questionnaire has proved to be a useful tool for evaluating and improving care quality in DUs.

Parasitic outbreak of the copepod Balaenophilus manatorum in neonate loggerhead sea turtles (Caretta caretta) from a head-starting program.

BACKGROUND: Diseases associated to external parasitosis are scarcely reported in sea turtles. During the last decades several organism have been documented as a part of normal epibiont community connected to sea turtles. The copepod Balaenophilus manatorum has been cited as a part of epibiont fauna with some concern about its parasitic capacity. This study serves three purposes, i.e. (i) it sheds light on the type of life style that B. manatorum has developed with its hosts, particularly turtles; (ii) it makes a cautionary note of the potential health risks associated with B. manatorum in sea turtles under captivity conditions and in the wild, and (iii) it provides data on effective treatments against B. manatorum. RESULTS: We report for the first time a massive infestation of the copepod B. manatorum and subsequent acute mortality in a group of loggerhead sea turtle hatchlings. Four-month-old turtles from a head-starting program started exhibiting excitatory and fin rubbing behavior preceding an acute onset of lethargy, skin ulceration and death in some animals. All the individuals (n = 57) were affected by severe copepod load and presented different degrees of external macroscopic skin lesions. The ventral area of front flippers, axillar and pericloacal skin were mostly affected, and were the main parasite distribution regions. Copepods were also detected on plastron and carapace sutures. The gut contents of B. manatorum reacted positively for cytokeratin, indicating consumption of turtle skin. Severe ulcerative necrotic dermatitis and large amount of bacteria presence were the major histopathological findings. CONCLUSIONS: Individual fresh water immersion for 10 min and lufenuron administration (0.1 ppm) to the water system every 2 weeks proved effective for removing turtle parasites and to control re-infestation, respectively. The results from our study clearly indicated that B. manatorum individuals consume turtle skin. The pathological effects of this agent and the potential implications in sea turtle conservation and management are discussed.

[Effectiveness of an intervention to improve safety culture. Less is more?] / Efectividad de una intervención para mejorar la cultura de seguridad. ¿Menos es más?

OBJECTIVE: To assess the impact of a long-term initiative to improve safety culture among professionals working in a Health Area, and to know their perceived usefulness. MATERIAL AND METHODS: An uncontrolled intervention study was designed in a public health care organization including a 3rd level hospital and 5,000 professionals. To measure the impact, the AHRQ Survey was conducted by telephone. A total of 7 dimensions of culture were measured, before starting the project (2012, n=100) and 3 years later (2015, n=207). Variations between 2012 and the respondents aware of the project in 2015 (RAP) were compared, as also between this last group and the rest of respondents (RNAP). The utility was assessed using a 5-item Likert scale, defining higher utility by medians 4 or higher. RESULTS: The response rates were above 80%. In 2015, the 41.5% of respondents were RAP (95%CI: 34.8-48.3), which was perceived as of high utility. Negative variations were detected in "sense of security" (-9.9%, P<.01, vs. 2012, and -4.2% between 2015 groups) and "feedback and communication errors" (-10.0% vs. 2012, and -8.9% between 2015 groups, P<.05). There was a not-significant positive variation in "openness in communication" (1.3% vs. 2012, and 6.9% between 2015 groups). The "management support" showed a not-significant improve in 2015 (37.0%, 95%CI: 30.9-43.1, in RAP; and 38.3%, 95%CI: 33.1-43.4, in RANP) in comparison to 2012 (31.4%, 95%CI: 28.4-39.7). CONCLUSIONS: A paradoxical worsening is detected in several dimensions, this probably due to immaturity of the organization and the instrument used. Thus, tools explicitly considering the degree of maturity may be more appropriate to measure cultural changes, although more studies are needed.

[Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update]. / Consenso sobre la vacunación anti-neumocócica en el adulto por riesgo de edad y patología de base. Actualización 2017.

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved.

Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value.

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.

[Can anybody understand the informed consent documents? A proposal to make it easier]. / ¿Pero alguien entiende los consentimientos informados? Una propuesta para facilitar su comprensión.

OBJECTIVE: To assess the readability of informed consent documents as written by doctors, by analysing the results and the differences between the sections of the document and services, with the aim of helping to improve them. MATERIAL AND METHODS: Descriptive study of the texts from 359 documents sent for accreditation in the Arrixaca Hospital (Murcia, Spain). Both length and readability are assessed. Length is measured in words (adequate up to 470, excessive over 940), and readability in INFLESZ points (suitable if over 55). RESULTS: Length ranged from 73 to 1018 words (mean 360, standard error 8.8, adequate length OR 3.66±0.81). The larger sections were "risks" and "nature of the procedure", and the shorter ones, "alternatives" and "contraindications", P<.0001. The INFLESZ value ranged from 18.1 to 86.4 points (mean 45.8, standard error 0.45), and was better in non-surgical services. Only 12.5% of the documents achieved an INFLESZ value over 55 (OR 0.12±0.03), with 70% in non-surgical procedures, P<.0001. The better readability sections were the "nature" and the "risks", and the worst ones, were "contraindications" and "alternatives", P<.0001. CONCLUSIONS: The length of proposed documents is adequate, but they are not sufficiently readable, especially if they come from surgical services. The section length is unbalanced, with "contraindications" and "alternatives" being shorter and more difficult to understand. It is essential to check the readability before using an informed consent document. For this purpose, tools like that proposed could be useful.

[Introduction of an accreditation system for hospital informed consent forms]. / Introducción de un sistema de acreditación para los documentos de consentimiento informado hospitalario.

OBJECTIVE: To describe an accreditation system for informed consent forms (ICF) in a tertiary hospital, as an intervention to improve their quality, and to check the improvements achieved. MATERIAL AND METHODS: Following an external evaluation of the ICF quality in a public hospital in Murcia (Spain), an accreditation committee set the ICF requirements and associated procedures. Effectiveness is assessed by comparing two external evaluations carried out by the EMCA Program (2011 and 2013) and based on 19 criteria and a sample of 60 ICF for every public hospital in Murcia Region. RESULTS: To be accredited, every ICF must meet the 19 external criteria plus 5 based on legibility, readability and scientific and technical validity. A form to fill in the contents of every ICF was agreed, which would be reviewed, approved and validated for five years. Before the implementation, 8.2 defects/ICF were detected. The accreditation system obtained an 89% improvement (0.9 defects/ICF) and achieved significant improvements in 18 criteria, 16 of which are benchmarked. DISCUSSION: The accreditation system achieved a substantial improvement in the ICF (obtaining a better result in external evaluations) and guarantees their contents, legibility and readability. This system needs to be extended to other hospitals, since it is not clear whether common ICFs would be suitable. However, this improvement is structural and does not guarantee that the overall information/consent procedure is done properly, thus complementary strategies for measurement and improvement are required.

Comparison of NITAG policies and working processes in selected developed countries.

BACKGROUND: Vaccines are specific medicines characterized by two country-specific market access processes: (1) a recommendation by National Immunization Technical Advisory Group (NITAG), and (2) a funding policy decision. OBJECTIVES: The objective of this study was to compare and analyze NITAGs of 13 developed countries by describing vaccination committees' bodies and working processes. METHODS: Information about NITAGs bodies and working processes was searched from official sources from June 2011 to November 2012. Retrieved information was completed from relevant articles identified through a systematic literature review and by information provided by direct contact with NITAGs or parent organizations. An expert panel was also conducted to discuss, validate, and provide additional input on obtained results. RESULTS: While complete information, defined as 100%, was retrieved only for the UK, at least 80% of data was retrieved for 9 countries out of the 13 selected countries. Terms of references were identified in 7 countries, and the main mission for all NITAGs was to provide advice for National immunization programs. However, these terms of references did not fully encompass all the actual missions of the NITAGs. Decision analysis frameworks were identified for 10 out of the 13, and all NITAGs considered at least four criteria for decision-making: disease burden, efficacy/effectiveness, safety and cost-effectiveness. Advices were published by most NITAGs, but few NITAGs published meeting agendas and minutes. Only the United States had open meetings. CONCLUSIONS: This study supports previous findings about the disparities in NITAGs processes which could potentially explain the disparity in access to vaccinations and immunization programs across Europe. With NITAGs recommendations being used by policy decision makers for implementation and funding of vaccine programs, guidances should be well-informed and transparent to ensure National Immunization Programs' (NIP) credibility among the public and health care professionals.