Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study.

BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.

Gamma Knife Surgery versus Linac for Brain Metastasis: Which Technique for Which Patient? Analysis of an Historical Cohort of 63 Consecutive Patients Harboring 130 Lesions

Objectives: We present the retrospective analysis of a single-institution experience for radiosurgery (RS) in brain metastasis (BM) with Gamma Knife (GK) and Linac. Methods: From July 2010 to July 2012, 28 patients (with 83 lesions) had RS with GK and 35 patients (with 47 lesions) with Linac. The primary outcome was the local progression-free survival (LPFS). The secondary outcome was the overall survival (OS). Apart a standard statistical analysis, we included a Cox regression model with shared frailty, to modulate the within-patient correlation (preliminary evaluation showed a significant frailty effect, meaning that the correlation within patient could be ignored). Results: The mean follow-up period was 11.7 months (median 7.9, 1.7-22.7) for GK and 18.1 (median 17, 7.5-28.7) for Linac. The median number of lesions per patient was 2.5 (1-9) in GK compared with 1 (1-3) in Linac. There were more radioresistant lesions (melanoma) and more lesions located in functional areas for the GK group. The median dose was 24 Gy (GK) compared with 20 Gy (Linac). The LPFS actuarial rate was as follows: for GK at 3, 6, 9, 12, and 17 months: 96.96, 96.96, 96.96, 88.1, and 81.5%, and remained stable till 32 months; for Linac at 3, 6, 12, 17, 24, and 33 months, it was 91.5, 91.5, 91.5, 79.9, 55.5, and 17.1%, respectively (p = 0.03, chi-square test). After the Cox regression analysis with shared frailty, the p-value was not statistically significant between groups. The median overall survival was 9.7 months for GK and 23.6 months for Linac group. Uni- and multivariate analysis showed a lower GPA score and noncontrolled systemic status were associated with lower OS. Cox regression analysis adjusting for these two parameters showed comparable OS rate. Conclusions: In this comparative report between GK and Linac, preliminary analysis showed that more difficult cases are treated by GK, with patients harboring more lesions, radioresistant tumors, and highly functional located. The groups look, in this sense, very heterogeneous at baseline. After a Cox frailty model, the LPFS rates seemed very similar (p < 0.05). The OS was similar, after adjusting for systemic status and GPA score (p < 0.05). The technical reasons for choosing GK instead of Linac were the anatomical location related to highly functional areas, histology, technical limitations of Linac movements, especially lower posterior fossa locations, or closeness of multiple lesions to highly functional areas optimal dosimetry with Linac

Comportamento da dose glandular versus contraste do objeto em mamografia: determinação de formalismo semi-empírico para diferentes combinações alvo-filtro

OBJETIVO: Verificar o efeito da mudança no contraste do objeto, tempo de exposição e dose de radiação quando diferentes espessuras de filtração de molibdênio (Mo) e ródio (Rh) são empregadas em mamógrafos. MATERIAIS E MÉTODOS: Realizaram-se medidas da exposição na entrada da pele com uma câmara de ionização para diferentes espessuras para os filtros de Mo e Rh. Para determinar a dose glandular média foi utilizado simulador de BR12 (50% tecido adiposo e 50% tecido glandular) de diferentes espessuras (4 cm e 8 cm). Energias na faixa de 24 kVp a 34 kVp foram empregadas e filmes Kodak MinR 2000 foram utilizados. RESULTADOS: Os resultados evidenciaram dados de contraste do objeto, dose glandular e tempo de exposição para diferentes espessuras de filtros adicionais e diferentes tensões. Esses dados indicaram aumento nos valores de contraste do objeto e tempo de exposição, com o aumento da espessura dos filtros. A dose glandular apresentou comportamento com diferentes tendências para cada caso analisado. Equações foram definidas para possibilitar a estimativa do contraste do objeto, dose glandular e tempo de exposição para os casos estudados. CONCLUSÃO: Os resultados possibilitaram a estimativa de equações que auxiliam na verificação do comportamento do contraste do objeto e da dose glandular para simuladores com espessura de 4 cm e 8 cm e para os filtros de Rh e Mo. Dessa forma, torna-se possível estimar a figura de mérito (razão entre o contraste do objeto e a dose glandular), podendo auxiliar na análise da relação risco-benefício dos casos estudados.

Análisis de la Fisioterapia Domiciliaria Versus la Fisioterapia Ambulatoria en las zonas básicas de salud de Burgete, Salazar e Isaba de Navarra.

Introducción: La población de Navarra tiene una tendencia hacia una población más anciana y con un aumento de patologías crónicas. Esto hace que aumente el número de discapacitados y como consecuencia incremente la demanda asistencial tanto de cuidadores como de profesionales y aumente el gasto sanitario. Por estos motivos el servicio de fisioterapia a domicilio puede ser una buena alternativa de trabajo, ya que con este servicio ayudaremos a disminuir la carga asistencial de los cuidadores, ayudándoles a manejar la situación, disminuiremos la carga asistencial de los profesionales y los gastos sanitario evitando reingresos. A su vez el realizar el tratamiento de Fisioterapia en el domicilio del paciente, es decir en su entorno, mejorara la adherencia al tratamiento y, por lo tanto, su implicación en alcanzar los objetivos terapéuticos planteados. Hipótesis: la fisioterapia domiciliaria (FD) mejora los resultados del tratamiento, la calidad de vida de los pacientes y cuidadores y estos resultados son similares o mejores en comparación con la rehabilitación ambulatoria y hospitalaria en los pacientes con accidente cerebrovascular (ICTUS), prótesis de cadera (PD) y prótesis de rodilla (PR) y con enfermedad pulmonar obstructiva crónica (EPOC). Los objetivos planteados son los siguientes: Objetivo principal: valorar si es factible introducir la rehabilitación domiciliaria en Navarra. Objetivos secundarios: a) Valorar si la FD mejora más la calidad de vida de los pacientes comparando con la rehabilitación en el Hospital Virgen del Camino (HVC) y de la Clínica Ubarmin de Navarra (CU). b) Comprobar si se reducirían costes sanitarios con el Programa Piloto de Fisioterapia Domiciliaria. c) Evaluar la carga del cuidador. d) Comprobar el número de reingresos hospitalarios realizando la Fisioterapia Domiciliaria. e) Valorar la autonomía en la capacidad de realizar las actividades básicas de la vida diaria (AVBD) con la FD en comparación con la rehabilitación en el HVC y la CU. f) Valorar si los pacientes con ICTUS consiguen mejores resultados cognitivos realizando la FD en vez de la rehabilitación en el HVC y la CU. g) Estimar si los pacientes con ICTUS y con PD o PR consiguen un mejor equilibrio y autonomía para realizar la marcha, cambiando el lugar de tratamiento del HVC y la CU a su domicilio. h) Valorar si el realizar la FD hace que los pacientes con EPOC disminuyan en el índice de BODE en comparación con los que realizan la rehabilitación en el HVC y la CU. i) Comparar la media de sesiones al alta del Proceso de Atención en Fisioterapia. Metodología: el estudio de investigación implica la confección de dos grupos donde el grupo control llevará a cabo un tratamiento de fisioterapia ambulatoria u hospitalaria, mientras que el grupo experimental hará tratamiento en ámbito domiciliario. La evaluación se llevará a cabo mediante diferentes escalas validadas, (Barthel, Tinetti, Minni mental test, índice de BODE, Escala de Sobrecarga del Cuidador de Zarit y SF-36) al inicio del estudio, a los 15 días, al mes, a los 3 meses y a los 6 meses. El lugar de estudio serán las zonas básicas de salud de Burguete, Salazar e Isaba. Criterios de inclusión: pacientes con ICTUS, PD y PR o con EPOC, mayores de 65 años, independientemente del sexo. Limitación para desplazarse a un centro de salud y un buen soporte socio-familiar. Criterios de exclusión: afectación cognitiva, enfermedades o complicaciones que impida la realización de la FD. Pacientes con EPOC, fumadores y con peligro de broncoespasmo. Falta de colaboración por parte del paciente. Análisis estadístico: Para el análisis estadístico se utilizara el programa estadístico SPSS (versión 20). Para obtener las conclusiones se realizaran las relaciones oportunas entre las diferentes variables explicadas anteriormente. En el caso de la relación entre variables cuantitativas se utilizará el coeficiente de correlación lineal de Pearson. En la relación entre variables cualitativas el Test chi-cuadrado de Pearson. Por último en la relación entre diferentes modalidades de variables se hará la comparación de medias, Z t-test o t- test.

Reinforcement versus Fluidization in Cytoskeletal Mechanoresponsiveness

Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

Regulation of Port Charges in Spain: Global versus Local Competition

This article examines the determinants of traffic volumes and the revenues per tonne generated by Spain’s port authorities. The interest of the study lies on the strong differences between port authorities in a context of strict regulation but that provides some scope for price competition. We find that port charges influence the amount of traffic that a port is able to generate. Furthermore, we find clear evidence of local price competition and report mixed results for global competition. Revenues per tonne are higher in ports operating more international regular lines and with multinational terminal operators, while they are lower in ports with nearby competing facilities and where the market share of the dominant shipping firm is high.

Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified.

AIMS: To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS: Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS: A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P>0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION: The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.

Effect of Antecolic versus Retrocolic Gastroenteric Reconstruction after Pancreaticoduodenectomy on Delayed Gastric Emptying: A Meta-Analysis of Six Randomized Controlled Trials.

BACKGROUND: One of the most frequent complications of pancreaticoduodenectomy (PD) is delayed gastric emptying (DGE). The study aim was to evaluate the impact of the type of gastro/duodenojejunal reconstruction (antecolic vs. retrocolic) after PD on DGE incidence. METHODS: A systematic review was made according to the PRISMA guidelines. Randomized controlled trials (RCTs) comparing antecolic vs. retrocolic reconstruction were included irrespective of the PD techniques. A meta-analysis was then performed. RESULTS: Six RCTs were included for a total of 588 patients. The overall quality was good. General risk of bias was low. DGE was not statistically significantly different between the antecolic and retrocolic group (OR 0.6, 95% CI 0.31-1.16, p = 0.13). The other main surgery-related complications (pancreatic fistula, hemorrhage, intra-abdominal abscess, bile leak and wound infection) were not dependent on the reconstruction route (OR 0.84, 95% CI 0.41-1.70, p = 0.63). No statistically significant difference in terms of length of hospital stay was found between the 2 groups. There was also no difference of DGE incidence if only pylorus-preserving PD was considered and between the DGE grades A, B or C. CONCLUSION: This meta-analysis shows that antecolic reconstruction after PD is not superior to retrocolic reconstruction in terms of DGE.

Air services on thin routes : Regional versus low-cost airlines

An examination of the impact in the US and EU markets of two major innovations in the provision of air services on thin routes - regional jet technology and the low-cost business model - reveals significant differences. In the US, regional airlines monopolize a high proportion of thin routes, whereas low-cost carriers are dominant on these routes in Europe. Our results have different implications for business and leisure travelers, given that regional services provide a higher frequency of flights (at the expense of higher fares), while low-cost services offer lower fares (at the expense of lower flight frequencies).

Fat oxidation over a range of exercise intensities: fitness versus fatness.

Maximal fat oxidation (MFO), as well as the exercise intensity at which it occurs (Fatmax), have been reported as lower in sedentary overweight individuals but have not been studied in trained overweight individuals. The aim of this study was to compare Fatmax and MFO in lean and overweight recreationally trained males matched for cardiorespiratory fitness (CRF) and to study the relationships between these variables, anthropometric characteristics, and CRF. Twelve recreationally trained overweight (high fatness (HiFat) group, 30.0% ± 5.3% body fat) and 12 lean males (low fatness (LoFat), 17.2% ± 5.7% body fat) matched for CRF (maximal oxygen consumption (V̇O2max) 39.0 ± 5.5 vs. 41.4 ± 7.6 mL·kg(-1)·min(-1), p = 0.31) and age (p = 0.93) performed a graded exercise test on a cycle ergometer. V̇O2max and fat and carbohydrate oxidation rates were determined using indirect calorimetry; Fatmax and MFO were determined with a mathematical model (SIN); and % body fat was assessed by air displacement plethysmography. MFO (0.38 ± 0.19 vs. 0.42 ± 0.16 g·min(-1), p = 0.58), Fatmax (46.7% ± 8.6% vs. 45.4% ± 7.2% V̇O2max, p = 0.71), and fat oxidation rates over a wide range of exercise intensities were not significantly different (p > 0.05) between HiFat and LoFat groups. In the overall cohort (n = 24), MFO and Fatmax were correlated with V̇O2max (r = 0.46, p = 0.02; r = 0.61, p = 0.002) but not with % body fat or body mass index (p > 0.05). Fat oxidation during exercise was similar in recreationally trained overweight and lean males matched for CRF. Consistently, substrate oxidation rates during exercise were not related to adiposity (% body fat) but were related to CRF. The benefits of high CRF independent of body weight and % body fat should be further highlighted in the management of obesity.

Sociolingüística versus política y planificación lingüísticas: distinciones entre los campos y nociones integradoras

En el marc de la visió del fenomen lingüístic com a complex més que no pas com a «objecte», l"aproximació sociolingüística se centra en la llengua i els seus contextos eco-socio-cognitius. Així, la perspectiva sociolingüística es constitueix ineluctablement de forma inter- i transdisciplinària, i se situa clarament en una cruïlla de camins i perspectives que ha d"interrelacionar. No obstant, avui dia la sociolingüística és encara una àrea fragmentada i amb moltes línies d"estudi poc integrades i comunicades, i per tant el seu repte actual i de cara al futur immediat és construir un marc teòric integrador propi en el qual puguin convergir els diferents angles i plans d"estudi. En aquesta recerca d"elements generals unificadors sobresurt una noció que podria actuar si més no d"element cohesionador, i és la que es refereix al fenomen de la sociosignificació extragramàtica relacionat amb la diversitat de «com diem les coses» els humans. Així en societats amb presència de llengües distintes, dir alguna cosa fent-ne servir una o altra pot ser considerat com a significatiu per als interlocutors, tal com pot succeir en el cas de la concurrència de distintes varietats geodialectals o sociodialectals, que poden ser valorades de diferent manera pels parlants. Així mateix, més en el pla interpersonal, la selecció de formes lingüístiques i paralingüístiques adequades és crucial si, per exemple, volem indicar enuig o bé alegria i actitud festiva. Aquesta perspectiva se situa més a prop del «gir cognitivista» en les ciències socioculturals, ja que postula la centralitat del cervell-ment en el control de la conducta humana i, per tant, del comportament lingüístic.