Prescripción enfermera en el entorno de las urgencias y emergencias. Marco conceptual vs entorno legislado en España

The prescription, widely discussed and defined conceptually in recent years in an environment of widening the spectrum of responsibilities nurse, has capacity for integration and definition in the area of accident and emergency care and carried out over the patient urgently, about emergencies and life-long commitment. Be necessary to frame throughout the legal framework, following the amendment of the Twelfth Additional Provision of Law 29/2006 of guarantees and rational use of drugs and medical devices, can be waived and implementation required, provided under model and through the nursing process and method and as an exponent and endorsementn of science and advanced clinical practice, to join the idea of interdisciplinary professional consensus that the law posed by the preparation and implementation of standardized protocols, algorithms and / or clinical practice guidelines in the context of what has come to be called "collaborative standard prescription": Prescription to the nurse in certain clinical situations in terms of a performance protocol, agreed with multidisciplinary team care health of the population (Group Protocols), which can be considered an intermediate step in the evolution towards independent nurse prescribing, providing nurses experience of a prescription under these protocols and demonstrating their capabilities.

Loco-regional administration of anticancer agents : isolated lung perfusion with doxorubicin hypoxic abdominal stop-flow perfusion with gemcitabine

SUMMARY Regional drug delivery is an approach designed to improve the selectivity of anticancer chemotherapy. The advantage of regional treatments lies in increasing the drug concentration in the affected organ, while the rest of the organism is spared, thus improving efficacy and limiting treatment toxicity. The goal of this thesis was to assess the distribution throughout the body and the disposition (pharmacokinetics) of two anticancer agents, doxorubicin and gemcitabine, administered by two different regional administration modalities: isolated lung perfusion (ILP) for pulmonary metastases from soft tissue sarcomas and abdominal stop-flow hypoxic perfusion for advanced pancreatic cancers, respectively. For this purpose, two high-performance liquid chromatography methods were developed and validated. The first enabled the determination of doxorubicin in four different biological matrices: serum, reconstituted effluent, tissues with low levels of doxorubicin and tissues with high levels of doxorubicin. The second allows the analysis of gemcitabine and its principal metabolite dFdU in plasma. The administration of doxorubicin by ILP was studied in three preclinical studies (one on pigs and two on rats). It was first shown that, regardless of the administration mode, doxorubicin was not homogeneously distributed throughout the lung and that some regions remained out of reach. Secondly, it was demonstrated that doxorubicin did not adequately reach the tumours despite very high levels found in the lung. Finally, an attempt to enhance the doxorubicin tumoural uptake by pharmacologic modulation using two P-glycoprotein inhibitors, cyclosporin and valspodar, was unsuccessful. The last part of this work involves the administration of gemcitabine by abdominal stop-flow as a part of a phase I clinical trial in patients with advanced pancreatic disease or resistant malignant ascites. The study has demonstrated that the regional exposure to gemcitabine was increased while the exposure of the entire organism was similar to standard intravenous administrations. From a toxicological perspective, the procedure was rather well tolerated. However, even if no clinical response is expected from a phase I study, no hints of clinical responses were unfortunately observed. In conclusion, even if loco-regional therapies may afford the pharmacological advantage of increasing anticancer drug levels at the tumour site, further studies of these investigational treatment modalities are warranted to ascertain whether they can provide a significant improvement of the cancer therapy for patients, in terms of treatment tolerability, improved responses and survival rates. RÉSUMÉ L'administration locorégionale d'agents anticancéreux est une approche destinée à augmenter la sélectivité du traitement. L'avantage des traitements régionaux repose sur le fait que la concentration du médicament cytostatique est augmentée dans l'organe où est localisée la tumeur, alors que le reste de l'organisme est épargné, améliorant ainsi en théorie l'efficacité du traitement et en limitant sa toxicité. Le but de ce travail de thèse avait pour objectif de préciser, la pharmacocinétique au sein de l'organisme de deux agents anticancéreux, la doxorubicine et la gemcitabine, administrés par deux types de perfusions loco-régionales: la perfusion isolée du poumon (ILP) pour les métastases pulmonaires de sarcomes des tissus mous, et la perfusion hypoxique (stop-flow) abdominale pour les cancers avancés du pancréas. Dans cette optique, deux méthodes de chromatographie liquide à haute performance ont été développées et validées. La première permet le dosage de la doxorubicine dans quatre milieux biologiques: le sérum, l'effluent reconstitué, ainsi que des tissus contenant des concentrations faibles et élevées en doxorubicine. La seconde méthode permet le dosage dans le plasma de la gemcitabine et de son principal métabolite, le dFdU. L'administration de doxorubicine par ILP a été étudiée dans trois études précliniques (une chez le porc et deux chez le rat). Il a été montré, dans un premier temps, que la doxorubicine n'était pas distribuée de façon homogène au sein du poumon, quel que soit son mode d'administration. Dans un deuxième temps, il a été démontré que le médicament n'atteignait pas les tumeurs de façon adéquate, malgré des concentrations très élevées au sein du tissu pulmonaire. Finalement, une tentative d'augmenter la pénétration tumorale de la doxorubicine par une modulation pharmacologique de la P-glycoprotéine en utilisant la cyclosporine et le valspodar n'a pas abouti. La dernière partie de ce travail concernait l'administration de gemcitabine par stop-flow abdominal dans le cadre d'une étude clinique de phase I menée auprès de patients atteints de cancers avancés du pancréas ou d'ascites malignes réfractaires. Cette étude a démontré que l'exposition régionale à la gemcitabine était augmentée, alors que l'exposition de l'organisme était similaire à une administration de dose standard par voie intraveineuse. D'un point de vue toxicologique la procédure fut relativement bien tolérée. Cependant, même s'il n'est pas attendu de réponses cliniques dans une étude de phase I, aucun signe de réponse au traitement n'a pu être malheureusement observé. En conclusion, même si les thérapies loco-régionales présentent -en théorie- l'avantage pharmacologique d'augmenter les taux du médicaments anticancéreux sur le site de la tumeur, d'autres études précliniques et cliniques sont nécessaires pour démontrer que ces nouvelles modalités de traitement, de nature investigationelle à présent, apportent une réelle amélioration pour la prise en charge des patients cancéreux, en terme de tolérance au traitement et de l'augmentation des taux de réponses et de survie.

Management of bleeding and coagulopathy following major trauma: an updated European guideline.

INTRODUCTION: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. METHODS: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

Nutrición enteral en el paciente neurológico: ¿es suficiente el contenido en vitamina D en las fórmulas de uso habitual?

INTRODUCTION Vitamin D deficiency produces inadequate bone mineralization, proximal muscle weakness, abnormal gait and increased risk of falls and fractures. Moreover, in epidemiological studies, has been associated with increased risk of cancer, autoimmune diseases, type 1 and 2 diabetes, rheumatoid arthritis, multiple sclerosis, infectious diseases, cardiovascular diseases and depression. When synthesis through the skin by sun exposure is not possible and the patient can not eat by mouth, as in the advanced stages of various neurological diseases, the supply of vitamin D has to be done by enteral nutrition. OBJECTIVES The aim of this study is to review the role of vitamin D in a common group of neurological conditions that often require artificial nutrition and analyze whether the vitamin D of different enteral nutrition formulas is adequate to meet the needs of this group of patients. RESULTS Numerous studies have shown the association between vitamin D deficiency and increased incidence of dementia, stroke and other neurodegenerative diseases. Interventions aimed to increase levels of vit. D and its effects on functional (falls, pain, quality of life) and cardiovascular goals (cardiovascular death, stroke, myocardial infarction, cardiovascular risk factors) have obtained as highlight data a clear reduction of falls and fractures, while the evidence for the other parameters studied is still limited and inconsistent. The content of calcium and vitamin D of enteral formulas is legislated in our country. The total amount of vitamin D for a daily intake of 1,500-2,000 kcal ranges between 300 and 1,600 IU/d (mean ± SD: 32.9 ± 8.5 mg/100 kcal) in the complete formulas for enteral nutrition most commonly used. 50% of the diets studied, for an intake of 2,000 kcal/d, and 90% for an intake of 1,500 kcal/d, provide less than 600 IU/d of vitamin D. DISCUSSION Some revised recently guidelines published recommendations of daily intake of vitamin D. The document published by the U.S. Institute of Medicine recommended for adults between 19 and 70 years, 600 IU/d and up from 70, proposes 800 IU/d of vitamin D. These amounts are deemed insufficient by other scientific societies to state that to achieve blood levels of 25 (OH) D equal or greater than 30 ng/ml may be required a daily intake of 1,500-2,000 IU and a number two or three times higher if previous deficiency exists. CONCLUSIONS Further controlled studies are needed to ascertain which is the appropriate dose of vitamin D in advanced stages of neurological disease, where sun exposure is difficult and unlikely. We suggest that the vitamin D content should probably be reconsidered in enteral nutrition formulas, which, in light of recent publications appear as clearly insufficient for standard energy intakes (1,500-2,000 kcal).

Navigator-gated coronary magnetic resonance angiography using steady-state-free-precession: comparison to standard T2-prepared gradient-echo and spiral imaging.

RATIONALE AND OBJECTIVES: Recent developments of magnetic resonance imaging enabled free-breathing coronary MRA (cMRA) using steady-state-free-precession (SSFP) for endogenous contrast. The purpose of this study was a systematic comparison of SSFP cMRA with standard T2-prepared gradient-echo and spiral cMRA. METHODS: Navigator-gated free-breathing T2-prepared SSFP-, T2-prepared gradient-echo- and T2-prepared spiral cMRA was performed in 18 healthy swine (45-68 kg body-weight). Image quality was investigated subjectively and signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and vessel sharpness were compared. RESULTS: SSFP cMRA allowed for high quality cMRA during free breathing with substantial improvements in SNR, CNR and vessel sharpness when compared with standard T2-prepared gradient-echo imaging. Spiral imaging demonstrated the highest SNR while image quality score and vessel definition was best for SSFP imaging. CONCLUSION: Navigator-gated free-breathing T2-prepared SSFP cMRA is a promising new imaging approach for high signal and high contrast imaging of the coronary arteries with improved vessel border definition.

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours.

BACKGROUND Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. METHODS Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5-12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. RESULTS Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in Cmax and AUC0-t were dose proportional for the 6-12 mg/m2 doses. CONCLUSION The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. TRIAL REGISTRATION The study was registered with ClinicalTrials.gov as NCT01755390.

Rationale and design of a randomized, double-blind, placebo controlled multicenter trial to study efficacy, security, and long term effects of intermittent repeated levosimendan administration in patients with advanced heart failure: LAICA study.

BACKGROUND Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation. METHODS The LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 μg/kg/min dose, without a loading dose, every 30 days, or placebo. RESULTS The main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events. CONCLUSIONS The LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Improving integrated care in chronic kidney failure patients with a standard-based interoperability framework.

This paper introduces the evaluation report after fostering a Standard-based Interoperability Framework (SIF) between the Virgen del Rocío University Hospital (VRUH) Haemodialysis (HD) Unit and 5 outsourced HD centres in order to improve integrated care by automatically sharing patients' Electronic Health Record (EHR) and lab test reports. A pre-post study was conducted during fourteen months. The number of lab test reports of both emergency and routine nature regarding to 379 outpatients was computed before and after the integration of the SIF. Before fostering SIF, 19.38 lab tests per patient were shared between VRUH and HD centres, 5.52 of them were of emergency nature while 13.85 were routine. After integrating SIF, 17.98 lab tests per patient were shared, 3.82 of them were of emergency nature while 14.16 were routine. The inclusion of a SIF in the HD Integrated Care Process has led to an average reduction of 1.39 (p=0.775) lab test requests per patient, including a reduction of 1.70 (p=0.084) in those of emergency nature, whereas an increase of 0.31 (p=0.062) was observed in routine lab tests. Fostering this strategy has led to the reduction in emergency lab test requests, which implies a potential improvement of the integrated care.

Correlation between TH1 response standard cytokines as biomarkers in patients with the delta virus in the western Brazilian Amazon

Hepatitis D virus (HDV) is endemic in the Amazon Region and its pathophysiology is the most severe among viral hepatitis. Treatment is performed with pegylated interferon and the immune response appears to be important for infection control. HDV patients were studied: untreated and polymerase chain reaction (PCR) positive (n = 9), anti-HDV positive and PCR negative (n = 8), and responders to treatment (n = 12). The cytokines, interleukin (IL)-2 (p = 0.0008) and IL-12 (p = 0.02) were differentially expressed among the groups and were also correlated (p = 0.0143). Future studies will be conducted with patients at different stages of treatment, associating the viral load with serum cytokines produced, thereby attempting to establish a prognostic indicator of the infection.

Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

Affymetrix Whole-Transcript Human Gene 1.0 ST array is highly concordant with standard 3' expression arrays.

The recently released Affymetrix Human Gene 1.0 ST array has two major differences compared with standard 3' based arrays: (i) it interrogates the entire mRNA transcript, and (ii) it uses DNA targets. To assess the impact of these differences on array performance, we performed a series of comparative hybridizations between the Human Gene 1.0 ST and the Affymetrix HG-U133 Plus 2.0 and the Illumina HumanRef-8 BeadChip arrays. Additionally, both RNA and DNA targets were hybridized on HG-U133 Plus 2.0 arrays. The results show that the overall reproducibility of the Gene 1.0 ST array is best. When looking only at the high intensity probes, the reproducibility of the Gene 1.0 ST array and the Illumina BeadChip array is equally good. Concordance of array results was assessed using different inter-platform mappings. Agreements are best between the two labeling protocols using HG-U133 Plus 2.0 array. The Gene 1.0 ST array is most concordant with the HG-U133 array hybridized with cDNA targets. This may reflect the impact of the target type. Overall, the high degree of correspondence provides strong evidence for the reliability of the Gene 1.0 ST array.

Combined modality treatment with full-dose chemotherapy and concomitant boost radiotherapy for advanced head and neck carcinoma

Résumé Le but de cette étude est d'évaluer la faisabilité et l'efficacité d'un traitement des carcinomes pharyngo-laryngés avancés par combinaison de chimiothérapie intensive associé à une radiothérapie accélérée. Vingt-trois patients ont été inclus (age médian 54 ans, entre 35 et 70 ans). Les localisations tumorales étaient l'hypopharynx (n=7), base de langue (n=10), nasopharynx (n=2) ou l'oesophage proximal (n.1), ou sans porte d'entrée (n=3). Le traitement comprend trois cycles de chimiothérapie (cisplatin 100mg/m2 à J1 ; 5-FU 1000mg/m2 par jour pendant 5 jours en perfusion continue, précédé par de l'amifostine 910mg/m2 ; répété toutes les trois semaines). La radiothérapie concomitante, accélérée (dose totale de 70Gy en 6 semaines) a été débuté au premier jour du deuxième cycle de chimiothérapie. Vingt et un patients ont pu achever la radiothérapie. Dix-huit patients étaient en rémission complète à la fin du traitement. Avec un suivi médian de 45 mois, le taux de survie globale atteint 56% (95% Cl, 32-79%). Le contrôle loco-régional était de 71% (95% CI, 52-91%). La toxicité associée au traitement consistait en une insuffisance rénale réversible (≥grade II) chez 9 patients (43%) et une agranulocytose fébrile chez 9 patients (43%). Tous les patients ont présenté une mucite modérée à sévère (grade II/III) et 19 patients ont montré une toxicité cutanée de grade III. En conclusion, le traitement combiné de radiothérapie accélérée avec une chimiothérapie concomitante à base de Cisplatin/5-FU full-dose avec amifostine est faisable. La toxicité est importante mais reste maîtrisable dans le cadre d'un centre multidisciplinaire. Le taux de survie globale à 4 ans est prometteur, la recherche en vue de traitements moins toxiques doit se poursuivre. Abstract The purpose of this study was to evaluate the feasibility and efficacy of a treatment concept combining three cycles of full-dose chemotherapy (CT) with concomitant accelerated uninterrupted radiotherapy (RI). Twenty- three patients (median age: 54 years, range: 35-70) with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were included. The primary tumor involved the hypopharynx (n=7), base of the tongue (n=10), nasopharynx (n=2) or upper esophagus (n=1) or its location was unknown (n=3). Treatment consisted of three cycles of chemotherapy (cisplatin 100 mg/m2 on day 1; 5-FU 1,000 mg/m2 per day for 5 days as a continuous infusion, preceded by amifostine 910 mg/m2). repeated every 3 weeks. Uninterrupted concomitant boost-accelerated RI (total dose of 70 Gy in 6 weeks) started together on day 1 of the second cycle. All but two patients received the full course of RT. Eighteen patients achieved complete remission (78%). At a median follow-up of 45 months the overall survival was 56% (95% c.i. 32-79%) and the loco-regional control 71% (95% c.i. 52-91%). Toxicity involved reversible renal insufficiency of grade II in 9 patients (39%) and neutropenic fever in 9 patients (39%). All patients suffered from moderate to severe mucositis (grade HMI), and 19 patients presented cutaneous toxicity grade III. Concomitant boost-accelerated RI combined with concurrent full-dose cisplatin/5-FU chemotherapy and amifostine is feasible with manageable, although substantial, toxicity. The overall survival of 4 years is promising. Newer regimens causing less acute mucosal and skin toxicity are needed.