Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Predictive Factors for Anxiety during Blood Sampling and Insertion of Peripheral Intravenous Catheters in Paediatric Patients in Spain.

INTRODUCTION: Invasive procedures for diagnosis purposes such as venepuncture and peripheral venous catheter insertion are painful procedures that cause great stress for paediatric patients. The objective of this study is to find out the factors that have an impact on the level of anxiety experienced by children undertaken these procedures. DESIGN AND METHODS: Prospective study, 359 children between 2 and 15 years old were included, treated in a tertiary reference hospital in the region of Navarra (Spain). The impact of the variables recorded was analysed using a regressive analysis, the Wong-Baker and FLACC scales were used to measure the level of pain and the PACBIS scale to measure the level of stress and anxiety. RESULTS: The average age of the participants was 7.93 years (SD: 4.04), with 51.8% (n = 186) boys and 48.2% (n = 173) girls. The mean value of pain recorded was 4.43 (SD:3.10). 45.7% (n = 123) of the venepuncture techniques was associated with minimum level of anxiety, including 11.1% of intravenous catheterization. Variables determining the anxiety has been detected such as age, sex, level of pain, parental conduct and time spent on the procedure. CONCLUSIONS: Paediatric patients experience high levels of anxiety when undergoing painful procedures which are conditioned by multifactorial reasons. The increase in stress is directly related to the older age (>6 years old) of the patient, and statistically significant by the female gender, the longer duration of the technique and the parental block. PRACTICE IMPLICATIONS: Healthcare professionals should work on some of the variables and apply measures aimed to mitigate anxiety levels. For example, reducing the duration of the procedure, training parents, and distracting techniques.

Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains.

One of the serious threats facing the administration of antiretroviral therapy to human immunodeficiency virus (HIV-1) infected patients is the reported increasing prevalence of transmitted drug resistance. However, given that HIV-1 drug-resistant strains are often less fit than the wild-type strains, it is expected that drug-resistant strains that are present during the primary phase of the HIV-1 infection are replaced by the fitter wild-type strains. This replacement of HIV-1 resistant mutations involves the emergence of wild-type strains by a process of backward mutation. How quickly the replacement happens is dependent on the class of HIV-1 mutation group. We estimate the backward mutation rates and relative fitness of various mutational groups known to confer HIV-1 drug resistance. We do this by fitting a stochastic model to data for individuals who were originally infected by an HIV-1 strain carrying any one of the known drug resistance-conferring mutations and observed over a period of time to see whether the resistant strain is replaced. To do this, we seek a distribution, generated from simulations of the stochastic model, that best describes the observed (clinical data) replacement times of a given mutation. We found that Lamivudine/Emtricitabine-associated mutations have a distinctly higher, backward mutation rate and low relative fitness compared to the other classes (as has been reported before) while protease inhibitors-associated mutations have a slower backward mutation rate and high relative fitness. For the other mutation classes, we found more uncertainty in their estimates.

Neoplasia curada. Un seguimiento que debe durar años / Cured malignancy: a follow-up that should last for years

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Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization.

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Th1-type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

Evolución clínica de la forma hiperaguda de la encefalomielitis aguda desmielinizante / Clinical outcome of the hyperacute form of acute disseminated encephalomyelitis

Introducción: La encefalomielitis aguda desmielinizante (EMAD) es una enfermedad inflamatoria mutifocal y monofásica del sistema nervioso central (SNC) que afecta a la sustancia blanca. La evolución suele ser favorable. Presentamos nuestra experiencia en el manejo de la EMAD de curso clínico hiperagudo. Pacientes y métodos: Revisión de 5 casos de EMAD que se encontraban en coma en el momento del ingreso en la Unidad de Cuidados Intensivos Pediátricos (UCIP). Se describen los resultados epidemiológicos, clínicos, microbiológicos y los hallazgos de resonancia magnética (RM), así como el tratamiento y la evolución de dichos pacientes. Resultados: La edad media fue de 5,2 años (100% varones). Ningún caso presentó criterios de leucoencefalitis aguda hemorrágica. Todos los pacientes ingresaron en coma y precisaron ventilación mecánica controlada. Todos presentaron fiebre previamente al ingreso. El intervalo entre el primer síntoma de afectación neurológica y el coma fue ≤ 24 h. En 3 casos se objetivó alteración bioquímica del LCR. El estudio inmunológico del LCR detectó bandas oligoclonales en un paciente. En la primera RM, la sustancia blanca supratentorial y núcleos basales se mostraron afectados en todos los casos y 3 presentaron afectación medular. Todos recibieron tratamiento con metilprednisolona a dosis altas. Cuatro recibieron tratamiento con inmunoglobulina G a dosis altas y uno, plasmaféresis. Dos pacientes fallecieron durante su estancia en UCIP. Las lesiones radiológicas de sustancia blanca persistieron al alta. A los 9 meses, los 3 supervivientes presentaban un Glasgow Outcome Scale de 5 puntos y no habían presentado recaídas. Conclusiones: Existen formas hiperagudas de EMAD que se acompañan de una mortalidad elevada. A corto plazo, la mejoría clínica no se acompaña de una regresión paralela de las lesiones detectables en la RM(AU)

Introduction: Acute disseminated encephalomyelitis (ADEM) is an inflammatory disease that damages the white matter of the central nervous system. Its clinical course is monophasic and multifocal. The outcome is usually favourable. We report our experience in the management of the hyperacute form of ADEM. Patients and methods: A retrospective chart review was performed on five patients admitted in coma with a diagnosis of ADEM in the Paediatric Intensive Care Unit (PICU). We describe their epidemiological, clinical, microbiological, magnetic resonance imaging features and their treatment and outcomes. Results: The mean age was 5.2 years and all were male. None of them fulfilled radiologic criteria for acute haemorrhagic leukoencephalitis. At admission all patients were in a coma, and all were on controlled mechanical ventilation support. Before their admission all patients had fever. In all cases the time between the first neurological symptom and coma was ≤ 24hours. The cerebrospinal fluid examination was abnormal in three patients, and in one case, oligoclonal bands were detected. The first brain magnetic resonance imaging (MRI) showed white matter and basal ganglia lesions in all patients, and in three cases the spinal medulla was affected by demyelination. All patients were treated with a course of high-dose methylprednisolone. Four patients were also treated with high-dose immunoglobulins, and one of them received plasmapheresis. Two patients died, and one patient had severe sequelae at discharge from the PICU. At discharge the lesions in the white matter were still present in the MRI. After nine months the three survivors had a Glasgow Outcome Scale score of five and no one relapsed. Conclusions: There is a hyperacute clinical form of ADEM which has a high mortality rate. In the short term, the clinical improvement of hyperacute ADEM is not accompanied by a decrease of severity of the brain MRI(AU)

[Clinical outcome of the hyperacute form of acute disseminated encephalomyelitis]. / Evolución clínica de la forma hiperaguda de la encefalomielitis aguda desmielinizante.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is an inflammatory disease that damages the white matter of the central nervous system. Its clinical course is monophasic and multifocal. The outcome is usually favourable. We report our experience in the management of the hyperacute form of ADEM. PATIENTS AND METHODS: A retrospective chart review was performed on five patients admitted in coma with a diagnosis of ADEM in the Paediatric Intensive Care Unit (PICU). We describe their epidemiological, clinical, microbiological, magnetic resonance imaging features and their treatment and outcomes. RESULTS: The mean age was 5.2 years and all were male. None of them fulfilled radiologic criteria for acute haemorrhagic leukoencephalitis. At admission all patients were in a coma, and all were on controlled mechanical ventilation support. Before their admission all patients had fever. In all cases the time between the first neurological symptom and coma was ≤ 24hours. The cerebrospinal fluid examination was abnormal in three patients, and in one case, oligoclonal bands were detected. The first brain magnetic resonance imaging (MRI) showed white matter and basal ganglia lesions in all patients, and in three cases the spinal medulla was affected by demyelination. All patients were treated with a course of high-dose methylprednisolone. Four patients were also treated with high-dose immunoglobulins, and one of them received plasmapheresis. Two patients died, and one patient had severe sequelae at discharge from the PICU. At discharge the lesions in the white matter were still present in the MRI. After nine months the three survivors had a Glasgow Outcome Scale score of five and no one relapsed. CONCLUSIONS: There is a hyperacute clinical form of ADEM which has a high mortality rate. In the short term, the clinical improvement of hyperacute ADEM is not accompanied by a decrease of severity of the brain MRI.

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

Measuring social networks in British primary schools through scientific engagement.

Primary schools constitute a key risk group for the transmission of infectious diseases, concentrating great numbers of immunologically naive individuals at high densities. Despite this, very little is known about the social patterns of mixing within a school, which are likely to contribute to disease transmission. In this study, we present a novel approach where scientific engagement was used as a tool to access school populations and measure social networks between young (4-11 years) children. By embedding our research project within enrichment activities to older secondary school (13-15) children, we could exploit the existing links between schools to achieve a high response rate for our study population (around 90% in most schools). Social contacts of primary school children were measured through self-reporting based on a questionnaire design, and analysed using the techniques of social network analysis. We find evidence of marked social structure and gender assortativity within and between classrooms in the same school. These patterns have been previously reported in smaller studies, but to our knowledge no study has attempted to exhaustively sample entire school populations. Our innovative approach facilitates access to a vitally important (but difficult to sample) epidemiological sub-group. It provides a model whereby scientific communication can be used to enhance, rather than merely complement, the outcomes of research.

HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen.

There is a need for new adjuvants that will induce immune responses to subunit vaccines. We show that a short peptide, named Hp91, whose sequence corresponds to an area within the endogenous molecule high mobility group box (HMGB1) protein 1 potentiates cellular immune responses to peptide antigen and cellular and humoral immune responses to protein antigen in vivo. Hp91 promoted the in vivo production of the immunomodulatory cytokines, IFN-γ, TNF-α, IL-6, and IL-12 (p70), as well as antigen-specific activation of CD8+ T cells. These results demonstrate the ability of a short immunostimulatory peptide to serve as an adjuvant for subunit vaccines.

[An unusual cause of failure of weaning from mechanical ventilation in an infant]. / Una causa inusual de fracaso del destete de la ventilación mecánica en un lactante.

The weaning process is a critical phase in patients undergoing mechanical ventilation. This process can be hampered by numerous causes, such as neuromuscular diseases and spinal muscular atrophy (SMA). We present a 6-month-old boy with respiratory distress, fever, marked hypotonia without motor developmental milestones, and areflexia. The patient showed progressive respiratory distress requiring mechanical ventilation. Definitive weaning was not achieved and the boy died from respiratory failure. Partial autopsy was performed with a diagnosis of SMA and genetic study of the parents. Neuromuscular diseases are an infrequent cause of respiratory insufficiency in suckling infants. The differential diagnosis is made between axonal and motor neuron diseases. The diagnosis was confirmed by muscular biopsy and genetic study.

Una causa inusual de fracaso del destete de la ventilación mecánica en un lactante / An unusual cause of failure of weaning from mechanical ventilation in an infant

El proceso de destete es una fase crítica del paciente tratado con soporte ventilatorio que puede verse dificultada por numerosas causas entre las que se encuentran las enfermedades neuromusculares, como la atrofia muscular espinal (AME). Lactante de 6 meses que presenta dificultad respiratoria y fiebre llamando la atención una marcada hipotonía generalizada sin logros motrices y arreflexia rotuliana. El niño sufre deterioro respiratorio con necesidad de asistencia ventilatoria mecánica sin lograrse un destete definitivo. Fallece por fallo respiratorio, realizándose necropsia parcial con diagnóstico de AME y estudio genético de progenitores. Las enfermedades neuromusculares son una causa poco frecuente de insuficiencia respiratoria en lactantes. Se realiza un diagnóstico diferencial entre las enfermedades de motoneurona, enfermedades axonales y enfermedades de placa motora. El diagnóstico fue confirmado por la biopsia muscular y el estudio genético

The weaning process is a critical phase in patients undergoing mechanical ventilation. This process can be hampered by numerous causes, such as neuromuscular diseases and spinal muscular atrophy (SMA). We present a 6-month-old boy with respiratory distress, fever, marked hypotonia without motor developmental milestones, and areflexia. The patient showed progressive respiratory distress requiring mechanical ventilation. Definitive weaning was not achieved and the boy died from respiratory failure. Partial autopsy was performed with a diagnosis of SMA and genetic study of the parents. Neuromuscular diseases are an infrequent cause of respiratory insufficiency in suckling infants. The differential diagnosis is made between axonal and motor neuron diseases. The diagnosis was confirmed by muscular biopsy and genetic study

Colangiocarcinoma infectado / Infected cholangiocarcinoma

Los colangiocarcinomas son tumores poco frecuentes y de crecimiento lento originados en el arbol biliar. Se localizan en tres regiones: intrahepáticos, extrahepáticos proximales, y extrahepáticos distales. La etiologia de la mayoría de los tumores biliares permanece indeterminada, aunque se han sugerido algunos factores de riesgo, como la litiasis, que puedan favorecer la transformación maligna. El pronóstico y las manifestaciones clínicas dependen de la localización anatómica, puediendo presentarse con sintomatología confusa o por medio de complicaciones como la sepsis. Presentamos un caso de colangiocarcinoma que debutó con colestasis y sepsis en una paciente colecistectomizada, tras colecistitis litiásica de laga evolución

Cholangiocarcinomas are malignancies of the biliary duct system. They are encountered in 3 geographic regions: intrahepatic, proximal extrahepatic, and distal extrahepatic. The etiology of most bile duct cancers remains undetermined but some risk factors, like gallstone, have been suggested to play a role by inducing malignant transformation. The prognosis and clinical manifestations depend on the anatomical location and clinical presentation may be confuses or by means of complications like sepsis. We present a case of cholangiocarcinoma which made debut with cholestasis and sepsis in a cholecystectomiced pacient, who had a long standing lithiasic cholecystitis