Assessment of pain relief after four botulinum toxin A injection cycles in patients with post-stroke lower limb spasticity: A prospective, observational study.

INTRODUCTION: Spasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity. METHODS: Prospective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0-10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0-100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey. RESULTS: Of 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0-10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection. CONCLUSION: BotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

Depressive symptoms and suicide attempts among farmers exposed to pesticides.

Pesticides safeguard crop health but may diminish cholinesterase activity in farmers, potentially leading to psychiatric disorders like depression and suicide attempts. This study, with 453 participants (225 pesticide-exposed farmers, 228 non-farmers) in Almería, Spain, aimed to investigate the presence of depressive symptoms and suicide attempts, the decrease acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, and their relationship with pesticide exposure in farmers. Depressive symptoms were evaluated using the Spanish adaptation of the Beck Depression Inventory, and blood samples were analyzed for AChE and BChE activity. Farmers showed significantly increased risk of moderate/severe depression and suicide attempts compared to non-farmers (OR = 2.18; p = 0.001), with highest risks observed among mancozeb users (OR = 2.76; p = 0.001 for depression) and malathion users (OR = 3.50; p = 0.001 for suicide attempts). Findings emphasize elevated depression and suicide risks among pesticide-exposed farmers, particularly associated with chlorpyrifos, mancozeb, and malathion exposure.

Image processing tools for the validation of CryoEM maps.

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two half-maps and the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.

Mean glandular dose in the mammary gland and dose of radiation in the thyroid gland and lens in women with and without breast implants during different modalities of mammography.

There have always been concerns about the secondary effects of diagnostic methods that use ionizing radiation. During mammography, the parameters to be concerned about are the mean glandular dose and the scatter dose. We evaluated the dose of radiation to the breast, thyroid gland, and lens in digital mammography in women with and without implants, in tomosynthesis in women with and without implants, and in contrast-enhanced mammography. MATERIALS AND METHODS: The study included 212 women with and without disease who were attended at the Centro Clínico de Estereotaxia, CECLINES, in Caracas, Venezuela, between June 2017 and August 2017; the women were classified into five groups according to the mammographic modality used to evaluate them and whether or not they had implants. The statistical analysis included descriptive statistics for the study population. We used the Mann-Whitney U to compare the mean glandular dose and dose in the thyroid gland and lens between groups. RESULTS: The mean glandular dose and the dose of radiation received in the thyroid and lens were within the acceptable range. In a few exceptions, the mean glandular dose per view was slightly higher than 3 mGy. The scatter dose to the thyroid gland and the lens during mammography has a very small contribution to the annual dose equivalent. CONCLUSION: The mean glandular dose and the scatter dose to the thyroid gland and lens delivered during tomosynthesis and 2D mammography in women with implants were higher than those delivered during other mammographic techniques in women without implants.

Mean glandular dose in the mammary gland and dose of radiation in the thyroid gland and lens in women with and without breast implants during different modalities of mammography. / Dosis glandular promedio en glándula mamaria y dosis de radiación en glándula tiroides y cristalino en mujeres con y sin implantes mamarios durante diferentes modalidades mamográficas.

There have always been concerns about the secondary effects of diagnostic methods that use ionizing radiation. During mammography, the parameters to be concerned about are the mean glandular dose and the scatter dose. We evaluated the dose of radiation to the breast, thyroid gland, and lens in digital mammography in women with and without implants, in tomosynthesis in women with and without implants, and in contrast-enhanced mammography. MATERIALS AND METHODS: The study included 212 women with and without disease who were attended at the Centro Clínico de Estereotaxia, CECLINES, in Caracas, Venezuela, between June 2017 and August 2017; the women were classified into five groups according to the mammographic modality used to evaluate them and whether or not they had implants. The statistical analysis included descriptive statistics for the study population. We used the Mann-Whitney U to compare the mean glandular dose and dose in the thyroid gland and lens between groups. RESULTS: The mean glandular dose and the dose of radiation received in the thyroid and lens were within the acceptable range. In a few exceptions, the mean glandular dose per view was slightly higher than 3mGy. The scatter dose to the thyroid gland and the lens during mammography has a very small contribution to the annual dose equivalent. CONCLUSION: The mean glandular dose and the scatter dose to the thyroid gland and lens delivered during tomosynthesis and 2D mammography in women with implants were higher than those delivered during other mammographic techniques in women without implants.

Developing µSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a viable diagnostic biomarker for the detection and treatment of prostate cancer. Although numerous imaging techniques and fluorescent probes have been developed, targeted imaging and intraoperative surgery continue to remain as a proof-of-concept with a severe lack of tools having high affinity and penetrative capacity. In vitro three-dimensional cell culture has gained immense interest in cancer research and drug discovery programs as it yields important physiological information and serves an excellent model for bioimaging and penetration analysis studies. Current techniques employed in spheroid formation include liquid overlay and hanging drop methods, both of which are low-yielding and technically demanding. We describe for the first time a simple-to-use platform, µSpherePlatform, an inexpensive, high-throughput method yielding morphologically homogeneous spheroids in bulk for analyzing penetrative capacity and imaging ability of PCa diagnostics. Microwell arrays made of agarose have been fabricated using a commercial hairbrush as a master template. This procedure has been described in detail, and arrays of spheroids (100-120 spheroids/6-well plate) with >95% success rates have been produced from PCa cell lines (LNCaP and DU-145). A PSMA-targeted fluorescent conjugate was synthesized and evaluated in the spheroids developed using µSpherePlatform by multiphoton imaging. A synthetic 3D scaffold strategy is reported herein, which (1) correlates perfectly with the in vivo model, (2) is amenable for automated analysis, (3) shows a negligible lot to lot variation, (4) is simplistic, (5) is useful for high-throughput assays, (6) is extremely compatible with imaging techniques, (7) generates PCa spheroids within 48 h, and (8) forms large size-controllable spheroids of diameter 500-1300 µm. The µSpherePlatform thus provides a significant contribution to multimodal analyses of cancer diagnostics and deep-tissue imaging studies.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

Statistical control of processes applied to geometric uncertainties for CTV expansion margins determination in prostate cancer patients treated with VMAT: a prospective study in 57 patients.

PURPOSE: To study the control graphs applicability for the geometric uncertainties of VMAT treatments in prostate cancer patients, and their use to verify the hypothesis of the data obtained randomness, to apply the margins of Van Herk expression. MATERIAL AND METHODS: During the first 5 days of treatment, and then once a week, a Kv CBCT was performed, compared with the simulation CT and adjusted the displacements, to determine the inter-fraction errors. Immediately after radiation therapy, another CBCT was performed (for intra-fraction errors). With these data, the X, R position control charts have been made. The patients, not maintained the deviations within the charts control limits, were called "anomalies". Then, we compared the deviations and margins calculated with the van Herk expression for all patients and for those without anomalies. RESULTS: The margins determined show appreciable differences if there were calculated for the total set of patients or for the set of them without anomalies in the control charts. For the overall set of patients, the lateral, longitudinal, and vertical margins were 0.45 cm, 0.52 cm, 0.56 cm, while for the set of patients without anomalies were 0.29 cm, 0.35 cm, and 0.38 cm. CONCLUSIONS: The use of control charts allows tracking geometric deviations both inter and intra-fraction, variability real-time control and to detect situations in which it can change for non-random reasons, and require immediate investigation. Maintaining geometric deviations in the control state decreases the margins needed to administer a high dose to CTV in a high percentage of cancer prostate patients.

Effectiveness of fentanyl pectin nasal citrate in controlling episodes of breakthrough cancer pain triggered by routine radiotherapy procedures.

PURPOSE: The aim of the study was to evaluate the effectiveness of fentanyl pectin nasal spray (FPNS) in controlling procedural breakthrough cancer pain (BTCP) in advanced cancer patients undergoing radiotherapy. MATERIALS AND METHODS: This study involved 62 advanced cancer patients, with well-controlled background pain, who presented BTCP associated to routine radiotherapy procedures, treated with FPNS according to our protocol of administration. The BPE intensity was measured using a visual analog scale (VAS). RESULTS: The BTCP was triggered during the computed tomography simulation (79.3%) or treatment delivery (20.7%). Patients indicated a mean VAS of 8.8 (range 7-10) when attempting the procedure. After 4.5 min (range 2-10) of the first FPNS dose, the majority of patients (85.5%) indicated a VAS of 4.3 (range 2-6). 15.5% of the patients did not respond after 15 min; requiring a second dose. All these patients responded, reporting a mean VAS of 4.2 (range 4-6) after 3.0 min (range 2-5) of the second dose. None of the patients required a third dose, nor reported an AE after the administration of FPNS. CONCLUSIONS: In our knowledge, our study is the one of highest recruitment, and with the fastest response of BTCP treated with FPNS reported in advanced cancer patients undergoing radiotherapy. FPNS has proven to be highly effective in reducing the intensity of procedural BTCP in a very short period of time.

Inflammation status in HIV-positive individuals correlates with changes in bone tissue quality after initiation of ART.

BACKGROUND: The mechanisms behind ART-induced bone changes in HIV-infected patients are poorly known. We aimed to analyse changes in inflammatory and bone markers in HIV after tenofovir disoproxil fumarate initiation, and the associations with changes in the bone strength parameters. METHODS: HIV-positive participants starting tenofovir disoproxil fumarate-based ART underwent dual-energy X-ray absorptiometry (QDR 4500 SL®, Hologic, Waltham, MA, USA) for bone mineral density (BMD), a microindentation test (OsteoProbe®, Active Life Scientific, Santa Barbara, CA, USA) for bone quality [bone material strength index (BMSi)] and phlebotomy at baseline and 48 weeks after ART. A panel of inflammatory biomarkers and bone turnover markers were measured by ELISA. HIV-negative controls underwent identical procedures once. Values are expressed as medians and IQRs, and non-parametric tests were used to perform the analysis. RESULTS: Twenty HIV-infected individuals and 20 HIV-negative control individuals were matched in terms of age and gender. HIV individuals showed higher levels of inflammatory markers. We found no differences in bone turnover markers. HIV-positive individuals presented lower BMSi values at baseline compared with controls [86 (83-90) versus 89 (88-93), respectively; P = 0.034]. We found no difference in BMD (at either of the sites evaluated). BMSi tended to increase with treatment. IL-1ß at baseline was positively correlated with changes in BMSi after ART (rho = 0.564, P = 0.014). Baseline levels of sclerostin tended to be negatively correlated with changes in BMSi (rho = -0.402, P = 0.097). We found a negative correlation between time since HIV diagnosis and changes in BMSi (rho = -0.466, P = 0.04). CONCLUSIONS: We observed a correlation between changes in bone quality and the inflammatory environment in HIV-positive individuals. Moreover, among the underlying mechanisms we highlight the Wnt pathway as having a potentially significant role in ART bone quality recovery.

Active study: undetected prevalence and clinical inertia in the treatment of breakthrough cancer pain (BTcP).

AIMS: To prove if there is clinical inertia in the identification and treatment of episodes of breakthrough cancer pain (BTcP), comparing actual results from clinical practice with clinical oncologists' prior perception. DESIGN: Observational and descriptive study, using information collected by practising medical oncologists, at three moments: (a) questionnaire regarding their professional judgement of the handling of patients with BTcP in their practice, (b) cross-sectional clinical screening, to detect possible existing cases of BTcP in a representative sample of their patients, (c) retrospective self-audit of clinical case histories of patients diagnosed with BTcP to find out about how it has been handled. PARTICIPANTS AND STUDY PERIOD: A random sample on a state level of 108 specialists in medical oncology. 540 patients who suffer some type of cancer pain on the designated study date for each specialist (July-December 2016). RESULTS: The global prevalence of BTcP in the study sample covered 91.3% of the patients who were suffering some type of cancer pain. Barely 2% of the doctors surveyed suspected figures around this mark. 40.9% of the cases had not been previously detected as BTcP by their doctors. Although 90% of the patients who had previously been diagnosed with BTcP received a specific analgesic treatment for the symptoms, 42% of those patients with known BTcP were not able to control their episodes of pain. CONCLUSIONS: Clinical inertia is a serious problem in the handling of BTcP in medical oncology services, where it is the subject of a significantly low level of detection and treatment, despite the contrasting perception of specialists.

Requirements and energy efficiency of Pelibuey and Katahdin non pregnant, non lactating ewes in Yucatan, Mexico / Requerimientos y eficiencia energética de ovejas Pelibuey y Katahdin no gestantes, no lactantes en Yucatán, México

Abstract Objective. To estimate metabolizable energy requirements for maintenance (MEm), energy efficiency of weight gain (EEWG) and fat thickness, in Pelibuey and Katahdin ewes in Yucatan, Mexico. Material and method. Eight non pregnant, non lactating, multiparous ewes, were feed at three intake levels with a diet containing 2.0 Mcal/Kg-1 of ME and 11 % of CP. Feed intake was measured daily, ewes weight and thickness of subcutaneous fat (SF) were determined every 14 days. The EMm was estimated by regressing values of live weight against metabolizable energy intake (MEI), EEWG was estimate as gram of weight gain per Mcal of MEI. Results. There were no differences between breeds in MEm (97±4 and 110±4 kcal/Kg0.75, for Pelibuey and Katahdin) and EEWG (58±8 and 63±8 g/Mcal of MEI, for Pelibuey and Katahdin); differences were found in SF (6.1±0.2 and 4.9±0.2 mm, for Pelibuey and Katahdin). Conclusions. The energy requirements for maintenance were similar in Pelibuey and Katahdin ewes in Yucatan, Mexico.

Resumen Objetivo. Estimar los requerimientos de energía metabolizable para el mantenimiento (MEm), le eficiencia energética del incremento de peso (EEWG) y el grosor de grasa, en ovejas Pelibuey y Katahdin en Yucatán, México. Materiales y método. Ocho ovejas multíparas no gestantes, no lactantes, fueron alimentadas a tres niveles de consumo con una dieta que contenía 2.0 Mcal/kg-1 de EM y 11% de PC. El consumo de alimento fue medido diariamente, el peso de ovejas y el grosor de grasa subcutánea (SF) se determinó cada 14 días. La MEm fue estimada por regresión de los valores de peso vivo contra el consumo de EM (MEI), la EEWG fue estimada como los gramos de ganancia de peso por Mcal de MEI. Resultados. No existieron diferencias entre razas en EMm (97±4 y 110±4 kcal/Kg0.75, para Pelibuey y Katahdin respectivamente) y EEWG (58±8 y 63±8 g/Mcal de MEI, para Pelibuey y Katahdin respectivamente); se encontraron diferencias en SF (6.1±0.2 y 4.9±0.2 mm, para Pelibuey y Katahdin respectivamente). Conclusiones. Los requerimientos de energía para mantenimiento fueron similares en las ovejas Pelibuey y Katahdin en Yucatán, México.

[The design of a population register on cerebral palsy: its application and analysis in Andorra and Navarre]. / Diseño de un registro de paralisis cerebral de ambito poblacional: aplicacion y analisis en Andorra y Navarra.

INTRODUCTION: Cerebral palsy describes a group of developmental and posture disorders, which cause a limitation of activity due to non-progressive damage occurring in the developing brain. A population register facilitates the identification of cerebral palsy cases within a specific geographic population. Its usefulness is recognized in the world literature but in Spain, published databases focus on the treatment or complications of cerebral palsy. AIMS: To propose a population register that can be useful in different areas of our environment and to evaluate its validity through its application in two differentiated and geographically delimited health areas. SUBJECTS AND METHODS: The registry consists of 124 items divided into seven sections: data on the child filiations, maternal history and parents' information, pregnancy and neonatal period data, diagnoses and classification, neuroimaging tests, therapeutic interventions and others. Patients attended in external consultations in Navarre and Andorra were included. RESULTS: In the register, 53 patients (52.8% females) were evaluated. 56.5% were premature. Spastic cerebral palsy is the most frequent presentation. 42% have associated epilepsy. CONCLUSIONS: The use of population registers allows a better knowledge of cerebral palsy as well as the evaluation and development of prevention strategies and optimization of care resources with objective data. It is necessary to generalize the use of this type of records in our environment.

TITLE: Diseño de un registro de paralisis cerebral de ambito poblacional: aplicacion y analisis en Andorra y Navarra.Introduccion. La paralisis cerebral describe un grupo de trastornos del desarrollo y la postura que causan una limitacion de la actividad debido a alteraciones no progresivas ocurridas en el cerebro en desarrollo. El registro poblacional facilita la identificacion de los casos de paralisis cerebral dentro de una poblacion geografica especifica. Esta reconocida su utilidad en la bibliografia, pero en España, las bases de datos publicadas se centran en el tratamiento o las complicaciones de la paralisis cerebral. Objetivos. Proponer un registro poblacional que pueda ser util en diferentes areas de nuestro entorno y evaluar su validez mediante su aplicacion en dos areas de salud diferenciadas y geograficamente delimitadas. Sujetos y metodos. El registro elaborado constaba de 124 items divididos en siete apartados: datos de filiacion del niño, historia materna e informacion de los padres, datos del embarazo y periodo neonatal, diagnosticos y clasificacion, pruebas de neuroimagen, intervenciones terapeuticas y otros. Se incluyo a los pacientes atendidos en consultas externas en Navarra y Andorra. Resultados. En el registro se evaluo a 53 pacientes (52,8% mujeres). El 56,5% fueron prematuros. La paralisis cerebral espastica es la presentacion mas frecuente. Un 42% asociaba epilepsia. Conclusiones. El uso de registros poblacionales permite un mejor conocimiento de la paralisis cerebral, asi como la evaluacion y el desarrollo de estrategias de prevencion y optimizacion de los recursos asistenciales con datos objetivos. Es necesaria la generalizacion del uso de este tipo de registros en nuestro entorno.

Effects of prenatal stress on anxiety- and depressive-like behaviours are sex-specific in prepubertal rats.

The foetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behaviour. The present study aimed to determine the physiological and behavioural effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 to 21, a critical period for foetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviours, as well as spontaneous social interaction. We also assessed maternal behaviours and 2 stress markers: basal vs acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behaviour, whereas both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation, as well as anxiety- and depressive-like behaviours, were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on hypothalamic-pituitary-adrenal (HPA) axis activity and on behaviour during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, and they were also more anxious and experienced depressive-like behaviours. These results are useful with respect to studying the neurobiological basis of childhood depression at a preclinical level.

Oncologist's knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study.

PURPOSE: Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP. METHODS: Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline. RESULTS: A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines. CONCLUSION: Despite oncologist's clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.

Liver-related mortality and hospitalizations attributable to chronic hepatitis C virus coinfection in persons living with HIV.

OBJECTIVES: The aim of this study was to compare liver-related mortality and liver-related hospitalizations for persons living with HIV (PLWH) with and without hepatitis C virus (HCV) exposure, and to estimate the fraction of liver disease attributable to chronic HCV coinfection. METHODS: An ambispective cohort study followed PLWH between 1993 and 2014. PLWH were classified into three groups: those who were HIV-monoinfected, those who cleared HCV spontaneously and those with chronic HCV coinfection. Liver-related mortality was estimated for the three groups and compared with the adjusted standardized mortality ratio. RESULTS: Data for 2379 PLWH were included in the study (1390 monoinfected individuals, 146 spontaneous HCV resolvers and 843 with chronic HCV coinfection). Global mortality was 33.8%, 21.4% of which was liver-related. Patients who died from liver-related causes were mostly on antiretroviral therapy and had an undetectable HIV viral load when they died. The liver-related mortality rate in those with chronic HCV coinfection was 10.01 per 1000 patient-years vs. 3.84 per 1000 patient-years in the HIV-monoinfected group (P < 0.001). The adjusted standardized mortality ratio in the chronically HCV-coinfected group was 4.52 (95% confidence interval 2.98-5.86). The fractions of liver-related mortality and liver-related hospitalizations attributable to chronic HCV coinfection were 0.61 and 0.74, respectively. There were no differences in liver-related events between HIV-monoinfected individuals and those who spontaneously cleared HCV. CONCLUSIONS: Chronic HCV infection increases the risk of liver-related mortality and liver-related hospitalizations in PLWH, despite good control of HIV infection. Sixty per cent of liver-related mortality in chronically HCV-coinfected PLWH could be attributable to chronic HCV infection. The effect of mass HCV eradication with new therapies should be evaluated.

Role of Periostin in Uncontrolled Asthma in Children (DADO study).

BACKGROUND AND OBJECTIVE: Asthma is the most common chronic disease in children. Cases of severe asthma (SA) are underdiagnosed. Periostin is a biomarker for SA in adults, but its role in children is poorly understood. Objectives: The aims of the study were to estimate the percentage of cases of uncontrolled severe asthma (UcSA) in children with poorly controlled asthma and to evaluate the role of periostin as a biomarker. MATERIAL AND METHODS: We performed an observational study in children aged 5 to 14 years with poorly controlled asthma. Demographic and clinical data were collected in addition to the results of the lung function test, the fraction of exhaled nitric oxide, the skin prick test, total IgE, specific IgE, blood eosinophil count, serum periostin, treatment, asthma control, and quality of life. Variables were compared between the group with UcSA and the other children. RESULTS: Fifty children with poorly controlled asthma (72% male) were included. Nineteen children (38%) had UcSA. Most children had limitations in their activities of daily living and had visited the emergency department. In addition, 38% were hospitalized. Quality of life was poor. Only 42% of the children received appropriate treatment. The UcSA group was more likely to have a total IgE >500 kUA/mL (52.6% vs 19%, P=.02) and less likely to have serum periostin >1000 ng/mL (31.2% vs 63%, P=.04). CONCLUSIONS: In our setting, 38% of children with poorly controlled asthma have UcSA, which is associated with higher levels of total serum IgE and lower levels of serum periostin.

Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial.

PURPOSE: TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. METHODS: Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. RESULTS: The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related ≥Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. CONCLUSIONS: In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified. CLINICALTRIALS. GOV STUDY NUMBER: NCT01607957.