Aportación de la radioterapia guiada por la imagen al tratamiento del cáncer de próstata

Objetivo: Demostrar que la verificación mediante Cone Beam CT (CBCT) en una serie de pacientes tratados con radioterapia externa 3D (RTE3D) por su cáncer de próstata (CP) se relaciona con una reducción de los niveles de toxicidad aguda y tardía. Material y Métodos: Se ha realizado un estudio retrospectivo no aleatorizado de 2 grupos homogéneos de pacientes tratados entre 2005 y 2008, 46 pacientes verificados mediante Electronic Portal Devices (EPIC) y 48 verificados mediante CBCT (Electa Synergy), con una mediana de edad de 67 años (42-85 años). Recibieron RTE3D por CP estadio localizado ( T1-T3b N0 M0 ), prescribiéndose las mismas dosis, simulados y planificados con los mismos criterios y en los mismos equipos (Electa Precise plan), con una mediana de seguimiento de 24 meses (12 a 54 m). Los criterios de exclusión fueron: tratamiento con anticoagulantes orales, antecedentes de cirugía rectal o prostática, enfermedad inflamatoria intestinal o conectivopatías. Todos los pacientes siguieron un mismo protocolo (dieta laxante suave, laxantes, vejiga llena) con objetivo de intentar mantener estables el contenido rectal y vesical. Se determinó mediante consultas médicas (semanal, mensual, trimestral, semestral) la toxicidad urinaria y gastro-intestinal según las escalas CTCAE.3 y RTOG . Se realizó un análisis estadístico de los datos estableciendo un nivel de confianza del 95%, p<0.005 ha implicado la significación estadística. Resultados y discusión: Con una mediana de seguimiento global de 24 meses (24 meses en el grupo verificado mediante imagen portal y 18 en el verificado mediante CBCT) los niveles de proctitis G2, sangrado rectal G2, toxicidad GU G2 han sido respectivamente 19,56%, 15,21% y 15,2% en el primer grupo frente a 4,17%, 2,08%, 8,33% en el segundo. Así aparece de manera estadísticamente significativa una menor proctitis total y tardía (p 0.008, p 0.032), menor sangrado rectal tardío (p 0.041), menor fisura anal (p 0.038), menor hematuria total y aguda (p 0.027, p 0.022), menor frecuencia urinaria total y aguda (p 0.027 p 0.022) y menor incontinencia urinaria total (p 0.038). No apareció evidencia estadísticamente significativa de menor toxicidad a nivel de disuria aguda y tardía, en relación al TMN, Gleason, PSA ni en función del grado de estabilidad según el protocolo de nivel de acción del CBCT. Conclusiones: La verificación mediante CBCT en esta serie de pacientes, se asocia a una menor toxicidad de manera estadísticamente significativa, pese a haber empleado un protocolo para mantener estables el contenido vesical y rectal, lo que justifica su empleo. Un seguimiento mayor sería necesario para valorar su impacto a nivel de control bioquímico.Objective: Demonstrate that verification through cone beam CT in a series of patients treated with external 3D radiotherapy (3DRT) for prostate cancer (PC) is related to a reduction in levels of acute and late-onset toxicity. Materials and Methods: Non-randomized, retrospective study of two homogenous groups of patients treated between 2005 and 2008 has been undertaken. 46 patients were verified using EPID, and 48 through CBCT. The median age of these patients was 67 years (42-85). These patients recieved 3DRT for localized stage PC (T1-T3bN0M0), and prescribed the same doses, simulated, planned with the same criteria and with the same equipment. The median monitoring time was 24 months. The exclusion criteria were: treatment with oral anticoagulants, rectal or prostatic surgery, inflammatory intestinal or connective disease. All patients followed the same protocol, with the objective of maintaining rectal and vesical content stable. Urinary and gastro-intestinal toxicity was determined through medical consultations according to the CTCAE.3 and RTOG scales. Statistical analysis of data was undertaken, establishing a confidence level of 95%, p<0.005 being the statistical significance. Results y Discussion: With a median follow up of 24 months the levels G>2 of proctitis, rectal bleeding, and GU toxicity were respectively 19.56%, 15.21% and 15.2% en the first group, compared with 4.17%, 2.08% and 8.33% in the second. Statistically, significantly less total and acute proctitis (p 0.008, p 0.032), late onset rectal bleeding (p 0.041), anal fissure (p 0.038), total and acute haematuria (p 0.027), total and acute urinary frequency (p 0.027, p 0.022) and total urinary incontinence (p 0.038) was observed. There was no statistically significant evidence of a lowering in toxicity in terms of stability according to the protocol of the action level of CBCT. Conclusion: Verification through CBCT in this series of patients is associated with a statistically significant lowering in levels of toxicity, even with use of a protocol to maintain vesical-rectal content stable in both groups. This justifies its use. Greater monitoring would be necessary in order to assess the impact of verification at the level of biochemical control

Using the Social-Local-Mobile App for Smoking Cessation in the SmokeFreeBrain Project: Protocol for a Randomized Controlled Trial

Background: Smoking is considered the main cause of preventable illness and early deaths worldwide. The treatment usually prescribed to people who wish to quit smoking is a multidisciplinary intervention, combining both psychological advice and pharmacological therapy, since the application of both strategies significantly increases the chance of success in a quit attempt. Objective: We present a study protocol of a 12-month randomized open-label parallel-group trial whose primary objective is to analyze the efficacy and efficiency of usual psychopharmacological therapy plus the Social-Local-Mobile app (intervention group) applied to the smoking cessation process compared with usual psychopharmacological therapy alone (control group). Methods: The target population consists of adult smokers (both male and female) attending the Smoking Cessation Unit at Virgen del Rocío University Hospital, Seville, Spain. Social-Local-Mobile is an innovative intervention based on mobile technologies and their capacity to trigger behavioral changes. The app is a complement to pharmacological therapies to quit smoking by providing personalized motivational messages, physical activity monitoring, lifestyle advice, and distractions (minigames) to help overcome cravings. Usual pharmacological therapy consists of bupropion (Zyntabac 150 mg) or varenicline (Champix 0.5 mg or 1 mg). The main outcomes will be (1) the smoking abstinence rate at 1 year measured by means of exhaled carbon monoxide and urinary cotinine tests, and (2) the result of the cost-effectiveness analysis, which will be expressed in terms of an incremental cost-effectiveness ratio. Secondary outcome measures will be (1) analysis of the safety of pharmacological therapy, (2) analysis of the health-related quality of life of patients, and (3) monitoring of healthy lifestyle and physical exercise habits. Results: Of 548 patients identified using the hospital’s electronic records system, we excluded 308 patients: 188 declined to participate and 120 did not meet the inclusion criteria. A total of 240 patients were enrolled: the control group (n=120) will receive usual psychopharmacological therapy, while the intervention group (n=120) will receive usual psychopharmacological therapy plus the So-Lo-Mo app. The project was approved for funding in June 2015. Enrollment started in October 2016 and was completed in October 2017. Data gathering was completed in November 2018, and data analysis is under way. The first results are expected to be submitted for publication in early 2019. Conclusions: Social networks and mobile technologies influence our daily lives and, therefore, may influence our smoking habits as well. As part of the SmokeFreeBrain H2020 European Commission project, this study aims at elucidating the potential role of these technologies when used as an extra aid to quit smoking

A Clinical Decision Support System (KNOWBED) to Integrate Scientific Knowledge at the Bedside: Development and Evaluation Study

[Background] The evidence-based medicine (EBM) paradigm requires the development of health care professionals’ skills in the efficient search of evidence in the literature, and in the application of formal rules to evaluate this evidence. Incorporating this methodology into the decision-making routine of clinical practice will improve the patients’ health care, increase patient safety, and optimize resources use.[Objective] The aim of this study is to develop and evaluate a new tool (KNOWBED system) as a clinical decision support system to support scientific knowledge, enabling health care professionals to quickly carry out decision-making processes based on EBM during their routine clinical practice.[Methods] Two components integrate the KNOWBED system: a web-based knowledge station and a mobile app. A use case (bronchiolitis pathology) was selected to validate the KNOWBED system in the context of the Paediatrics Unit of the Virgen Macarena University Hospital (Seville, Spain). The validation was covered in a 3-month pilot using 2 indicators: usability and efficacy.[Results] The KNOWBED system has been designed, developed, and validated to support clinical decision making in mobility based on standards that have been incorporated into the routine clinical practice of health care professionals. Using this tool, health care professionals can consult existing scientific knowledge at the bedside, and access recommendations of clinical protocols established based on EBM. During the pilot project, 15 health care professionals participated and accessed the system for a total of 59 times.[Conclusions] The KNOWBED system is a useful and innovative tool for health care professionals. The usability surveys filled in by the system users highlight that it is easy to access the knowledge base. This paper also sets out some improvements to be made in the future.This project has received funding from the Andalusian Ministry of Health from Spain (reference PIN-0213-2016), and FEDER funds.Peer reviewe

Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG MultidisciplinaryWorking Group

Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patientsThis research was funded by AstraZenec

The genetics of self-reported trait impulsivity: Contribution of catecholaminergic gene variants in European ancestry individuals

Increased trait impulsivity is a core element in several mental disorders. Given the durable and consistent nature of trait impulsivity, studies have explored its relation to stable biological measures. Variation in catecholaminergic neurotransmission by genetic variants could be one of these biological substrates. Here, 905 participants of European-ancestry completed the Barratt Impulsiveness Scale–11 and were genotyped in three single nucleotide polymorphisms related to catecholaminergic neurotransmission: the DRD2/ ANKK Taq1A, the C957T DRD2 and the Val158Met of the COMT gene. We found significant main effects of Val158Met and C957T on BIS-11 score. Also, interactions with gender were significant in both SNPs with a tendency to slightly different genotype and allele associations with the BIStotal score between male and female participants. Whereas in females, higher impulsivity scores were obtained by participants with the Val158Met heterozygous genotype (Met/Val), data indicate a trend towards a higher impulsivity score in male Val-allele carriers. In the case of C957T, only a tentative association between male Tallele carriers and higher impulsivity scores in comparison to CC genotype carriers could be established. No significant associations were found between BIS-11 and Taq1A. We provide further evidence for a gender-specific implication of Val158Met and C957T in trait impulsivity

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption

Study of the synergistic impact of Fe3O4, Na2CO3 and organic C on kaolin-based lightweight aggregates by a DOE (Mixture Experiments) approach

The compositional synergies involved in the thermal formation of lightweight aggregates (LWAs) have been investigated through four pure phases: non-expansive kaolin (K); cork powder (C); sodium carbonate (N) and magnetite-Fe3O4 (M). Mixture Experiments has been applied for formulation, modeling and optimization. LWAs have been manufactured from 36 starting mixtures and the main technological properties have been characterized: bloating index (BI), particle density (ρrd), water absorption (WA24) and crushing strength (S). Maximum BI and WA24 together with minimum density are associated with the addition of a significant amount of iron phase in combination with small proportions of organic carbon (Optimal [BI > 60%]: 56.0% K + 40.2% M + 3.9% C + 0% N), while S increases antagonistically with expansion. Iron reduction by incomplete combustion of C appears to be critical in pore formation and concomitant bloating. N has enhanced the sphericity of the expanded specimens. The contrast between experimental and estimated data has shown that the models have generally performed very well.This research was conducted as a part of the ECO-MET-AL Project, PID2019-109520RB-I00 / AEI / 10.13039/501100011033, “Can industrial and mining metalliferous wastes produce green lightweight aggregates? Applying the Circular Economy” funded by the Spanish Ministry of Science, Innovation and Universities and ERDF funds, framed in the “Ayudas a Proyectos I + D + i en el marco de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I + D + i y de I + D + i orientada a los Retos de la Sociedad, Convocatoria 2019”

Simulation study of resistor networks applied to an array of 256 SiPMs

[EN] In this work we describe a procedure to reduce the number of signals detected by an array of 256 Silicon Photo-multipliers (SiPMs) using a resistor network to divide the signal charge into few readout channels. Several configurations were modeled, and the pulsed signal at the readout contacts were simulated. These simulation results were experimentally tested on a specifically designed and manufactured set of printed circuit boards. Three network configurations were modeled. The modeling provided encouraging results for all three configurations. The measurements on the prototypes constructed for this study, however, provided useful position-sensitivity for only one of the network configurations. The lack of input signal amplification into the networks, the SiPM dark current, as well as the complexity of an eight layers board with parasitic capacitances, could have caused the degradation of resolving the impact photon position. This is hard to overcome with external printed circuit boards and components.This work was supported by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I) under Grant FIS2010-21216-CO2-01, the Valencian Local Government under Grant PROMETEO 2008/114 and through the JAE-Predoc grant from CSIC (BOE 29/01/2010).Gonzalez, A. J., Moreno, M., Barbera, J., Conde, P., Hernandez, L., Moliner, L., . . . Benlloch, J. M. (2013). Simulation study of resistor networks applied to an array of 256 SiPMs. IEEE Transactions on Nuclear Science, 60(2), 592-598. doi:10.1109/TNS.2012.2226051S59259860

A Mobile Health Solution Complementing Psychopharmacology-Supported Smoking Cessation: Randomized Controlled Trial

Background: Smoking cessation is a persistent leading public health challenge. Mobile health (mHealth) solutions are emerging to improve smoking cessation treatments. Previous approaches have proposed supporting cessation with tailored motivational messages. Some managed to provide short-term improvements in smoking cessation. Yet, these approaches were either static in terms of personalization or human-based nonscalable solutions. Additionally, long-term effects were neither presented nor assessed in combination with existing psychopharmacological therapies. Objective: This study aimed to analyze the long-term efficacy of a mobile app supporting psychopharmacological therapy for smoking cessation and complementarily assess the involved innovative technology. Methods: A 12-month, randomized, open-label, parallel-group trial comparing smoking cessation rates was performed at Virgen del Rocío University Hospital in Seville (Spain). Smokers were randomly allocated to a control group (CG) receiving usual care (psychopharmacological treatment, n=120) or an intervention group (IG) receiving psychopharmacological treatment and using a mobile app providing artificial intelligence–generated and tailored smoking cessation support messages (n=120). The secondary objectives were to analyze health-related quality of life and monitor healthy lifestyle and physical exercise habits. Safety was assessed according to the presence of adverse events related to the pharmacological therapy. Per-protocol and intention-to-treat analyses were performed. Incomplete data and multinomial regression analyses were performed to assess the variables influencing participant cessation probability. The technical solution was assessed according to the precision of the tailored motivational smoking cessation messages and user engagement. Cessation and no cessation subgroups were compared using t tests. A voluntary satisfaction questionnaire was administered at the end of the intervention to all participants who completed the trial. Results: In the IG, abstinence was 2.75 times higher (adjusted OR 3.45, P=.01) in the per-protocol analysis and 2.15 times higher (adjusted OR 3.13, P=.002) in the intention-to-treat analysis. Lost data analysis and multinomial logistic models showed different patterns in participants who dropped out. Regarding safety, 14 of 120 (11.7%) IG participants and 13 of 120 (10.8%) CG participants had 19 and 23 adverse events, respectively (P=.84). None of the clinical secondary objective measures showed relevant differences between the groups. The system was able to learn and tailor messages for improved effectiveness in supporting smoking cessation but was unable to reduce the time between a message being sent and opened. In either case, there was no relevant difference between the cessation and no cessation subgroups. However, a significant difference was found in system engagement at 6 months (P=.04) but not in all subsequent months. High system appreciation was reported at the end of the study. Conclusions: The proposed mHealth solution complementing psychopharmacological therapy showed greater efficacy for achieving 1-year tobacco abstinence as compared with psychopharmacological therapy alone. It provides a basis for artificial intelligence–based future approaches. Trial Registration: ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/NCT03553173 International Registered Report Identifier (IRRID): RR2-10.2196/12464H2020 European Commission research and innovation program grant agreement 68112

Can statistical methods optimize complex multicomponent mixtures for sintering ceramic granular materials? A case of success with synthetic aggregates

The relationship between the proportions of multicomponent mixtures with the technological properties of ceramic granular materials (synthetic aggregates) has been studied using statistical methods. The four phases involved in the formulations have been: kaolin (K) as aluminosilicate source; cork powder (C) as organic carbon source; sodium carbonate (N) as flux and pyrite (P) as source of iron and sulfur. The Mixture Experiments - Design of Experiments (ME-DOE) has been the statistical methodology applied from the initial configuration of the 36 starting formulations to the final validation of the models and optimums. After granulation, artificial aggregates have been obtained by sintering in a rotary kiln, and their main technological properties have been determined. Bloating index (BI), particle density (ρrd), water absorption (WA24) and crushing strength (S) were selected as the four key characteristics to be modeled and optimized, using response surface and effect plots to assess the effect of K, C, N and P on such properties. 32 out of 36 starting varieties met the density criteria for lightweight aggregates. In the optimum formulations obtained, the minimum percentage of K was 83 wt%, so that the variations in the percentages of P, C and N were the critical variables for determining the final properties of the aggregate. The contrast between experimental and estimated data has shown that the models fit adequately, indicating that this type of approach may have enormous potential for future research on artificial aggregates and other ceramic materialsThis research was conducted as a part of the ECO-MET-AL Project, PID2019-109520RB-I00 / AEI / 10.13039/501100011033, “Can industrial and mining metalliferous wastes produce green lightweight aggregates? Applying the Circular Economy” funded by the Spanish Ministry of Science, Innovation and Universities and ERDF funds, framed in the “Ayudas a “Proyectos I + D + i" en el marco de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I + D + i y de I + D + i orientada a los Retos de la Sociedad, Convocatoria 2019”. Thanks also to the SCAI of the University of Jaén, the University of Castilla-La Mancha and the University of Málaga for their service