Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and Vomiting: A Randomized Controlled Trial.

BACKGROUND Evidence suggests that cannabinoids can prevent chemotherapy-induced nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been suggested for the prevention of postoperative nausea and vomiting (PONV), but evidence is very limited and inconclusive. To evaluate the effectiveness of IV THC in the prevention of PONV, we performed this double-blind, randomized, placebo-controlled trial with patient stratification according to the risk of PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25% compared with placebo. METHODS With IRB approval and written informed consent, 40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo at the end of surgery before emergence from anesthesia. The primary outcome parameter was PONV during the first 24 hours after emergence. Secondary outcome parameters included early and late nausea, emetic episodes and PONV, and side effects such as sedation or psychotropic alterations. RESULTS The relative risk reduction of overall PONV in the THC group was 12% (95% confidence interval, -37% to 43%), potentially less than the clinically significant 25% relative risk reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of the effect of treatment group on overall PONV by logistic regression adjusted for anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to 4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and mainly consisted of sedation and confusion that were not tampered by the effects of anesthesia. The study was discontinued after 40 patients because of the inefficacy of THC against PONV and the finding of clinically unacceptable side effects that would impede the use of THC in the studied setting. CONCLUSIONS Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high-risk patients.

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

BPA qualtitative and quantitative assessment associated with orthodontic bonding in vivo

OBJECTIVE To assess the in vivo amount of BPA released from a visible light-cured orthodontic adhesive, immediately after bracket bonding. METHODS 20 orthodontic patients were recruited after obtaining informed consent. All patients received 24 orthodontic brackets in both dental arches. In Group A (11 patients), 25 ml of tap water were used for mouth rinsing, whereas in Group B (9 patients) a simulated mouth rinse formulation was used: a mixture of 20 ml de-ionized water plus 5 ml absolute ethanol. Rinsing solutions were collected before, immediately after placing the orthodontic appliances and after washing out the oral cavity and were then stored in glass tubes. Rinsing was performed in a single phase for 60s with the entire volume of each liquid. The BPA analysis was performed by gas chromatography-mass spectrometry. RESULTS An increase in BPA concentration immediately after the 1st post-bonding rinse was observed, for both rinsing media, which was reduced after the 2nd post-bonding rinse. Water exhibited higher levels of BPA concentration than water/ethanol after 1st and 2nd post-bonding rinses. Two-way mixed Repeated Measures ANOVA showed that the primary null hypothesis declaring mean BPA concentration to be equal across rinsing medium and rinsing status was rejected (p-value <0.001). The main effects of the rinsing medium and status, as well as their interaction were found to be statistically significant (p-values 0.048, <0.001 and 0.011 respectively). SIGNIFICANCE A significant pattern of increase of BPA concentration, followed by a decrease that reached the initial values was observed. The amount of BPA was relatively low and far below the reference limits of tolerable daily intake.

Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters

OBJECTIVE To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. MATERIALS AND METHODS Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19-52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. RESULTS The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. CONCLUSIONS One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Intravenous Iodinated Contrast Agents Amplify DNA Radiation Damage at CT

PURPOSE To determine the effect of the use of iodinated contrast agents on the formation of DNA double-strand breaks during chest computed tomography (CT). MATERIALS AND METHODS This study was approved by the institutional review board, and written informed consent was obtained from all patients. This single-center study was performed at a university hospital. A total of 179 patients underwent contrast material-enhanced CT, and 66 patients underwent unenhanced CT. Blood samples were taken from these patients prior to and immediately after CT. In these blood samples, the average number of phosphorylated histone H2AX (γH2AX) foci per lymphocyte was determined with fluorescence microscopy. Significant differences between the number of foci that developed in both the presence and the absence of the contrast agent were tested by using an independent sample t test. RESULTS γH2AX foci levels were increased in both groups after CT. Patients who underwent contrast-enhanced CT had an increased amount of DNA radiation damage (mean increase ± standard error of the mean, 0.056 foci per cell ± 0.009). This increase was 107% ± 19 higher than that in patients who underwent unenhanced CT (mean increase, 0.027 foci per cell ± 0.014). CONCLUSION The application of iodinated contrast agents during diagnostic x-ray procedures, such as chest CT, leads to a clear increase in the level of radiation-induced DNA damage as assessed with γH2AX foci formation.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014.

Renal Blood Oxygenation Level-dependent Imaging in Longitudinal Follow-up of Donated and Remaining Kidneys

Purpose To determine renal oxygenation changes associated with uninephrectomy and transplantation in both native donor kidneys and transplanted kidneys by using blood oxygenation level-dependent (BOLD) MR imaging. Materials and Methods The study protocol was approved by the local ethics committee. Thirteen healthy kidney donors and their corresponding recipients underwent kidney BOLD MR imaging with a 3-T imager. Written informed consent was obtained from each subject. BOLD MR imaging was performed in donors before uninephrectomy and in donors and recipients 8 days, 3 months, and 12 months after transplantation. R2* values, which are inversely related to tissue partial pressure of oxygen, were determined in the cortex and medulla. Longitudinal R2* changes were statistically analyzed by using repeated measures one-way analysis of variance with post hoc pair-wise comparisons. Results R2* values in the remaining kidneys significantly decreased early after uninephrectomy in both the medulla and cortex (P < .003), from 28.9 sec(-1) ± 2.3 to 26.4 sec(-1) ± 2.5 in the medulla and from 18.3 sec(-1) ± 1.5 to 16.3 sec(-1) ± 1.0 in the cortex, indicating increased oxygen content. In donors, R2* remained significantly decreased in both the medulla and cortex at 3 (P < .01) and 12 (P < .01) months. In transplanted kidneys, R2* remained stable during the first year after transplantation, with no significant change. Among donors, cortical R2* was found to be negatively correlated with estimated glomerular filtration rate (R = -0.47, P < .001). Conclusion The results suggest that BOLD MR imaging may potentially be used to monitor renal functional changes in both remaining and corresponding transplanted kidneys. (©) RSNA, 2016.

Focal Epilepsy: MR Imaging of Nonhemodynamic Field Effects by Using a Phase-cycled Stimulus-induced Rotary Saturation Approach with Spin-Lock Preparation.

Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC-SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. (©) RSNA, 2016 Online supplemental material is available for this article.

Salud e interculturalidad : un estudio en una población migrante en Mendoza

Los objetivos propuestos en la investigación han posibilitado identificar y documentar las barreras de acceso y los factores de riesgo en los cuidados de salud en ginecología y obstetricia y evaluar la situación sociofamiliar en la población migrante instrumentando acciones de inclusión en el sistema de salud de la provincia en aquellas pacientes que requirieron una atención de mayor complejidad. La experiencia de trabajo interdisciplinario en una comunidad ha posibilitado estudiar a 99 mujeres en edad fértil, en un 45% de origen boliviano, con alta vulnerabilidad social que habitan en el Distrito Belgrano de Guaymallén. Se realizó un estudio protocolizado, descriptivo y observacional con entrevistas semiestructuradas y control ginecológico, con toma de muestras para Papanicolaou y colposcopía en un consultorio que se instaló en el jardín maternal. Se aplicó un consentimiento informado a todas las mujeres antes de la realización de los estudios. La lectura de las muestras y los estudios específicos incluyeron mamografías y ecografías que se realizaron en los servicios de anatomía patológica y rayos del Hospital Universitario. El equipo del Hospital Universitario que concurrió a terreno estuvo formado por ginecólogos, trabajadores sociales, enfermeros y alumnos de las carreras de grado.

Estudio de distribución y frecuencia de caries en preescolares de alto riesgo social

Objetivos: El presente trabajo establece en el escenario local, un patrón de distribución y severidad de caries en una población de riesgo social de niños preescolares, datos necesarios para la programación de recursos en programas de salud bucal Método: estudio descriptivo, correlacional y transversal sobre muestra intencionada de 150 niños preescolares de 4 y 5 años de edad, de ambos sexos, con actividad de caries, pertenecientes a escuelas públicas, del ámbito urbano-marginal-Distrito Pedro Molina-Mendoza. Rep. Argentina, cuyos padres hubieron firmado el consentimiento informado. Se registraron las lesiones de caries según diente y sitio, y la severidad según ICDAS II (Pitts, 2004). Se establecieron distribución de frecuencias para las variables diente, sitio y categoría de ICDAS II. Para establecer asociaciones entre variables se aplicó prueba de chi cuadrado, con un nivel de significación de 0.05. Resultados: 1º y 2º molares temporarios son los más afectados, principalmente 75 y 85. El valor 6 de ICDAS II es el más frecuente, seguido por valores 3 y 5. El 84 presenta mayor frecuencia de valores grado 6. La superficie oclusal es la más afectada (42.6%). Existe asociación entre diente y categoría de ICDAS II y entre diente y sitio de la lesión para 55, 52, 51, 61, 62, 63 y 64, 84 y 75. Conclusiones: la distribución y severidad de caries en denticióntemporaria de los niños estudiados evidencia una alta frecuencia de lesiones de caries en molares, y una necesidad de tratamiento complejo involucrando para su resolución niveles de atención sanitaria II y III que deberá encontrar como contraparte un sistema sanitario preparado para su resolución.

Consentimiento informado

La profesión de odontólogo se ejerce a través de numerosos actos que requieren de la responsabilidad del profesional, relacionado con distintos problemas que ocurren en el quehacer diario en relación a la aprobación por parte del paciente. El consentimiento informado constituye un acto jurídico que debe reunir características propias.

Quien puede querer, quiso? El consentimiento sexual como problema en el tratamiento judicial de los delitos sexuales, Bs. As. 1863-1921

En los últimos años, los delitos sexuales se han convertido en objeto de preocupación para la sociedad; esto se vio reforzado por las nuevas formas de pensar y vivir las relaciones humanas inter e intra-género-s y especialmente las elecciones sexuales. En este trabajo propongo volver a poner en debate algunas cuestiones que hacen al problema de la definición jurídico-social y a la comprensión del "consentimiento" en el contexto específico de los expedientes seguidos por delitos sexuales en el ámbito de la provincia de Buenos Aires, entre 1863 y 1921, teniendo en cuenta la importancia que este concepto tiene para la definición de los delitos sexuales como tales. También se tomarán en cuenta algunos escritos de la época que permiten conocer la circulación de ideas en el ámbito específico del derecho y la medicina legal. Al mismo tiempo, pretendo poner en tensión las ideas sociales y culturales que aparezcan reflejadas en las fuentes respecto de qué es, cómo se otorga y cuándo puede hablarse de un efectivo consentimiento, así como de su contrario. Poniendo en juego las subjetividades propias de los participantes en el proceso. Resaltando la centralidad de esta cuestión en el mismo tanto para la definición de una víctima como para la caracterización de los acusados

Quien puede querer, quiso? El consentimiento sexual como problema en el tratamiento judicial de los delitos sexuales, Bs. As. 1863-1921

En los últimos años, los delitos sexuales se han convertido en objeto de preocupación para la sociedad; esto se vio reforzado por las nuevas formas de pensar y vivir las relaciones humanas inter e intra-género-s y especialmente las elecciones sexuales. En este trabajo propongo volver a poner en debate algunas cuestiones que hacen al problema de la definición jurídico-social y a la comprensión del "consentimiento" en el contexto específico de los expedientes seguidos por delitos sexuales en el ámbito de la provincia de Buenos Aires, entre 1863 y 1921, teniendo en cuenta la importancia que este concepto tiene para la definición de los delitos sexuales como tales. También se tomarán en cuenta algunos escritos de la época que permiten conocer la circulación de ideas en el ámbito específico del derecho y la medicina legal. Al mismo tiempo, pretendo poner en tensión las ideas sociales y culturales que aparezcan reflejadas en las fuentes respecto de qué es, cómo se otorga y cuándo puede hablarse de un efectivo consentimiento, así como de su contrario. Poniendo en juego las subjetividades propias de los participantes en el proceso. Resaltando la centralidad de esta cuestión en el mismo tanto para la definición de una víctima como para la caracterización de los acusados

Quien puede querer, quiso? El consentimiento sexual como problema en el tratamiento judicial de los delitos sexuales, Bs. As. 1863-1921

En los últimos años, los delitos sexuales se han convertido en objeto de preocupación para la sociedad; esto se vio reforzado por las nuevas formas de pensar y vivir las relaciones humanas inter e intra-género-s y especialmente las elecciones sexuales. En este trabajo propongo volver a poner en debate algunas cuestiones que hacen al problema de la definición jurídico-social y a la comprensión del "consentimiento" en el contexto específico de los expedientes seguidos por delitos sexuales en el ámbito de la provincia de Buenos Aires, entre 1863 y 1921, teniendo en cuenta la importancia que este concepto tiene para la definición de los delitos sexuales como tales. También se tomarán en cuenta algunos escritos de la época que permiten conocer la circulación de ideas en el ámbito específico del derecho y la medicina legal. Al mismo tiempo, pretendo poner en tensión las ideas sociales y culturales que aparezcan reflejadas en las fuentes respecto de qué es, cómo se otorga y cuándo puede hablarse de un efectivo consentimiento, así como de su contrario. Poniendo en juego las subjetividades propias de los participantes en el proceso. Resaltando la centralidad de esta cuestión en el mismo tanto para la definición de una víctima como para la caracterización de los acusados