An intergenerational programme delays health impairment in nursing home residents: the Duplo project

Purpose To analyse whether an intergenerational programme in which students interacted with institutionalised older persons had any impact on the older persons’ functional status. Methods Each academic year, a group of older adults living in nursing homes were divided into two arms. For the next four months, the first group received daily visits from a group of students during which they followed a pre-established activity plan, whilst the other arm proceeded with their normal activity. After 4 months, the groups crossed over, and the second arm received the student visits, whilst the first group returned to their normal activity. A battery of tests was performed at inception, crossover and the end of the second period. The tests explored mobility (Timed Up-and-Go), cognition (Mini-Mental Examination), executive function (Frontal Assessment Battery) and mood (Geriatric Depression Scale). A dichotomous aggregate “significant impairment” variable was deemed to be present when there was at least a 20% loss of function (compared to the value at the beginning of the period) in any of the aforementioned tests. Results The study included 289 older adults who visited with 91 students. Subjects in the active phase had a lower incidence of significant impairment than those in the control phase (O.R. 0.90, p < 0.01). There were no significant differences in the individual variables.post-print900 K

Non-invasive monitoring of hypoxia-inducible factor activation by optical imaging during antiangiogenic treatment in a xenograft model of ovarian carcinoma

Open Access Article.Targeting the hypoxia response pathway and angiogenesis are two promising therapeutic strategies for cancer treatment. Their use as single strategies has important limitations. Thus, development of combined regimens has become an important step toward improving therapeutic efficacy. Also, non-invasive monitoring of the response to targeted biological therapies, as well as determination of the optimal schedule for combination regimens has become an active field of research over the last five years, with relevance for both preclinical and clinical settings. Here, we used an optical imaging method to non-invasively monitor the functional changes in HIF activity in response to antiangiogenic treatment in a xenograft model of human ovarian carcinoma. A bioluminescent reporter construct containing nine copies of the hypoxia response element upstream of the luciferase gene (9xHRE-luciferase) was characterized in vitro in a panel of tumor cell lines and in vivo in a subcutaneous xenograft model of ovarian carcinoma by means of optical imaging. We showed that in OVCAR-3 subcutaneous xenografts, the most abrupt change in the HIF functional reporter occurs before the onset of massive tumor growth. However, this system failed to detect hypoxia induced upon antiangiogenic treatment due to the compensating effects of increased hypoxia and decreased tumor cell viability caused by imbalanced neovascularization vs. tumor expansion. Therefore, the readout based on HIF functional reporter could be conditioned by the dynamics of tumor growth and angiogenesis, which is highly variable depending on the tumor type, tumor model and stage of progression.This study was supported by grants from the Ministerio de Ciencia y Tecnología/Ministerio de Ciencia e Innovación (SAF2008-03147 to LdP and SAF2010-19256 to BJ), Comunidad Autónoma de Madrid (S-SAL-0311_2006) and the 7th Research Framework Programme of the European Union (METOXIA, project ref. HEALTH-F2-2009-222741). B.M.P. and V.G. have been supported by a grant from the Comunidad Autónoma de Madrid (S-SAL-0311_2006).Peer Reviewe

Gestió de la caça : efectes col·laterals del subministrament de pinso

En zones rurals de tot el món la caça de mamífers herbívors té sovint una gran importància econòmica. Per això, està molt estès en aquestes zones l'ús de mesures de gestió que afavoreixin la supervivència i les bones condicions de les espècies d'interès cinegètic. Entre les mesures de gestió és freqüent l'aportació d'aliment suplementari, fet que podria causar una variació en la selecció de plantes per part dels herbívors suplementats. Aquest estudi analitza els efectes que el subministrament de pinso a una població de cérvol ibèric provoca de manera indirecta sobre el matollar mediterrani.En zonas rurales de todo el mundo la caza de mamíferos herbívoros tiene a menudo una gran importancia económica. Por ello, está muy extendido en estas zonas el uso de medidas de gestión que favorezcan la supervivencia y las buenas condiciones de las especies de interés cinegético. Entre las medidas de gestión es frecuente el aporte de alimento suplementario, lo que podría causar una variación en la selección de plantas por parte de los herbívoros suplementados. Este estudio analiza los efectos que el suministro de pienso a una población de ciervo ibérico provoca de manera indirecta sobre el matorral mediterráneo

Influence of Diagnostic Delay on Survival Rates for Patients with Colorectal Cancer

Colorectal cancer affects men and women alike. Sometimes, due to clinical-pathological factors, the absence of symptoms or the failure to conduct screening tests, its diagnosis may be delayed. However, it has not been conclusively shown that such a delay, especially when attributable to the health system, affects survival. The aim of the present study is to evaluate the overall survival rate of patients with a delayed diagnosis of colorectal cancer. This observational, prospective, multicenter study was conducted at 22 public hospitals located in nine Spanish provinces. For this analysis, 1688 patients with complete information in essential variables were included. The association between diagnostic delay and overall survival at five years, stratified according to tumor location, was estimated by the Kaplan-Meier method. Hazard ratios for this association were estimated using multivariable Cox regression models. The diagnostic delay ≥ 30 days was presented in 944 patients. The presence of a diagnostic delay of more than 30 days was not associated with a worse prognosis, contrary to a delay of less than 30 days (HR: 0.76, 0.64-0.90). In the multivariate analysis, a short delay maintained its predictive value (HR: 0.80, 0.66-0.98) regardless of age, BMI, Charlson index or TNM stage. A diagnostic delay of less than 30 days is an independent factor for short survival in patients with CRC. This association may arise because the clinical management of tumors with severe clinical characteristics and with a poorer prognosis are generally conducted more quickly.This study was supported by public grants from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90453, PI09/00910, PI09/90460, PI09/90490, PI13/01692, PI13/00013, PI18/01181, PI18/01589, PS0900805 & PI0900441) and was co-funded by the European Regional Development Fund.S

Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort

Objective The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. Methods This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan–Meier method and Cox regression models. Results According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21–1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51–0.76), age (>70 years: HR = 3.78; 95% CI: 1.94–7.36), need for help (yes: HR = 1.43; 95% CI: 1.17–1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16–1.82), tumour size (T3–T4: HR = 1.56; 95% CI: 1.22–1.99), nodule staging (N1–N2: HR = 2.46; 95% CI: 2.04–2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55–0.91). Conclusions There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.Funding for open Access charge: Universidad de Málaga / CBUA. This study was supported by public grant from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90460, PI/0990490, PI13/01692, PI13/00013, PI18/01181, Pi18/01589) and was co-funded by the European Regional Development fund

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Foraging sexual segregation in a Mediterranean environment: Summer drought modulates sex-specific resource selection

A large body of studies have linked sexualsegregation in dimorphic ungulates with differential resource selection and nutritional requirements of the sexes. However, detailed patterns of sexual dietary preferences have rarely been assessed as keystone mechanisms of sexualsegregation. We compared diet and nutritional selection by 3 sex-age classes in the Iberian red deer (Cervus elaphus hispanicus Hilzheimer) across reproductive states and according to seasonal fluctuations in resource availability in aMediterraneanenvironment. Foragingsegregation between sexes was found during rut when female/juvenile selection of shrubs was higher than that of males. Observed foraging patterns relate to a stronger selection of nitrogen, tannins and lignin by females and juveniles, and fibres by males. Our findings are associated to the Mediterranean climate, where rut and lactation concur with a shortage period, the particularly dry summer. Foragingsegregation between sexes during the rut could be shaped by a conjunction of factors such as the low quality of resources and different fitness enhancement strategies. We highlight both the importance of including the dietary component and providing a temporal framework when documenting ungulate sexualsegregation, and the interest of considering regional conditions when addressing management of ungulates with a wide distribution.LGB was supported by a post-doctoral fellowship from Junta de Comunidades de Castilla-La Mancha (JCCM), co-funded by the European Social Fund (ESF CLM 2007/2013). Financial support was provided by projects PBI-05-010, PREG-07-21, PAI08-0264-1987 (all granted by JCCM) and CGL2007-63707/BOS (granted by Ministerio de Educación y Ciencia and co-funded by the European Regional Development Fund, ERDF).Peer reviewe

Contrasting feeding patterns of native red deer and two exotic ungulates in a Mediterranean ecosystem

[Context]: Ungulates have been widely introduced in multiple ecosystems throughout the world due to their value as food and for sport hunting.The identification of for aging preferences of exotic and native ungulates livingin sympatry is, therefore, becoming increasingly important in order to assess potential impacts of introduced animals on the host ecosystem. [Aims]: To describe species-specific for aging strategies and infer resource selection overlap between native and exotic ungulates. [Methods]: We compared the trophic ecology of three sympatric ungulate species living in a Mediterranean landscape: the native Iberian red deer Cervus elaphus hispanicus, and two exotic bovids, the European mouflon Ovis orientalis musimon and the aoudad Ammotragus lervia. We simultaneously determined herbivore diet through analyses of botanical content in faeces and assessed the nutritional content of these diets. [Key results]: Higher selection of shrubs by deer was sustained throughout the year, while bovids showed seasonal shifts in forage selection. Both bovids displayed a selective dietary strategy directed towards a higher overall nutritional quality than that of deer. Divergent exploitation patterns between the studied cervid and bovids might be related to body mass and physiological adaptations to overcome secondary defence compounds of shrubs, and were largely affected by seasonal changes in the nutritional value of available vegetation. Ecological theory suggests that diet overlap should be greater between similar-sized species. Indeed, both exotics showed similar, sometimes overlapping, dietary patterns that could lead to potential competition in the use of resources. Native red deer preferences only showed some overlap with those of exotic mouflon under constrained summer conditions. [Conclusions]: Dietary overlap between deer and mouflon and between aoudad and mouflon during limiting summer conditions could entail a potential competitive interaction under more even densities of the study species, since a concurrent habitat overlap between those pairs of species has previously been reported. [Implications]: The outcomes of our study suggest the need for an integration of habitat and ungulate management. Management actions in Mediterranean rangelands should be directed towards protecting habitat conditions so that biodiversity is enhanced along with the presence of sustainable communities of large herbivores. Management directed towards ungulates should maintain moderate stocking rates and monitor and control introduced and native populations.MM and MS enjoyed PhD fellowships from the Junta de Comunidades de Castilla -La Mancha (JCCM), and the Spanish National Research Council (CSIC, I3P grant), respectively. LGB was supported by a post-doctoral fellowship from Junta de Comunidades de Castilla-La Mancha (JCCM). Financial support was provided by projects PBI-05-010, PREG-07-21, PAI08-0264-1987 (all granted by JCCM) and CGL2007-63707/BOS (granted by Ministerio de Educación y Ciencia and co-funded by the European Regional Development Fund, ERDF.Peer reviewe

Ecological effects of game management: does supplemental feeding affect herbivory pressure on native vegetation?

[Context]: Supplemental feeding of large mammalian herbivores is a common management tool mainly aimed at promoting healthy populations and at increasing productivity and trophy sizes. Such management measure may indirectly affect herbivore effects on plant communities through altered foraging patterns. The quantification of the ecological effects of large herbivore management is important for designing holistic management and conservation programs. [Aims]: Here we aimed at quantifying the ecological effects of supplemental feeding of Iberian red deer, Cervus elaphus hispanicus, on the composition of and on the browsing effects on Mediterranean woody plant community. [Methods]: An experiment was set up in a hunting rangeland located in central Spain, where female deer were kept in enclosures with either exclusive access to natural forages or with additional ad libitum access to a nutritionally rich concentrate. The experiment also included a control area where deer were absent. [Key results]: We observed significant differences in browsing impacts among the supplemented, non-supplemented and control areas, and such effect varied for the different plant species. Plant species which nutritional content complemented that of fodder were more highly consumed, for instance, Erica spp., which digestible fibre content is higher and N content lower than that of provided fodder. The presence of deer and the concentrate supplied, instead, did not influence the relative abundances of shrub species. [Conclusions]: Artificial supplemental feeding provided to ungulates led to increased browsing on plant species which nutritional composition complemented that of the supplement provided. [Implications]: So as to alleviate herbivory impact on all shrubs, we suggest that composition of supplemental feeding should adjust both to the natural forage availability and quality and to ungulate requirements across seasons.MM was supported by a Claude Leon Postdoctoral Fellowship and a PhD fellowship from Junta de Comunidades de Castilla-La Mancha (JCCM). MS enjoyed a fellowship funded by the Spanish National Research Council (CSIC, I3P grant). The experimental set up was established through an Agreement between Yolanda Fierro and UCLM. This study was supported by projects PBI-05-010 and PREG-07-21, both of them awarded by JCCM to JC.Peer Reviewe

ATIM-22. PROGNOSTIC VALUE OF PTEN LOSS IN NEWLY DIAGNOSED GBM PATIENTS TREATED WITH AUTOLOGOUS HEAT SHOCK PROTEIN VACCINE

Abstract INTRODUCTION: The safety and efficacy of a heat shock protein peptide complex- 96 vaccine (HSPPC-96, Prophage) has been previously studied in phase II single-arm trials for the treatment of newly diagnosed and recurrent glioblastoma (GBM). These studies demonstrated modest improvements in survival compared with historical standards. PTEN loss has been recently associated with immunoresistance in GBM patients, mediated in part by B7-H1. PTEN status has not shown clear prognostic value in GBM patients treated with standard of care therapies. The aim of this study is to evaluate the prognostic significance of PTEN status in newly diagnosed GBM patients treated with autologous HSP vaccine and standard chemoradiation. METHODS Our institutional cohort of patients enrolled in a single arm, phase II study of adult GBM patients treated with autologous HSP vaccine and standard chemoradiation (n=27) was analyzed. Differences in overall survival (OS) by PTEN status were evaluated via Kaplan-Meier curves and Log-rank test. RESULTS Median overall survival (n=27) was 26 months. 23 patients had PTEN status available. PTEN loss was found in 16 patients (69.6%) whereas retained PTEN was present in 7 patients (30.4%). Median OS was 59 months (95% CI, 0–120 months) in patients with retained PTEN and 23 months (95% CI, 15–30 months) in patients with PTEN loss. The difference in OS was statistically significant (p=0.037). CONCLUSION: Retained PTEN expression was associated with extended survival in GBM patients treated with HSP vaccine. This finding suggests that PTEN loss may be associated with resistance to vaccine treatment and emphasizes the need for subgroup analysis in further immunotherapy studies