Impact of patient and public involvement on enrolment and retention in clinical trials: Systematic review and meta-analysis

© Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Objective To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. Design Systematic review and meta-analysis. Data sources Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. Eligibility criteria Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). Data extraction and analysis Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. Results 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). Conclusions These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. Systematic review registration PROSPERO CRD42016043808

Marine Biodiversity in Juan Fernández and Desventuradas Islands, Chile: Global Endemism Hotspots

22 páginas, 6 tablas, 5 figurasThe Juan Fernández and Desventuradas islands are among the few oceanic islands belonging to Chile. They possess a unique mix of tropical, subtropical, and temperate marine species, and although close to continental South America, elements of the biota have greater affinities with the central and south Pacific owing to the Humboldt Current, which creates a strong biogeographic barrier between these islands and the continent. The Juan Fernández Archipelago has ~700 people, with the major industry being the fishery for the endemic lobster, Jasus frontalis. The Desventuradas Islands are uninhabited except for a small Chilean military garrison on San Félix Island. We compared the marine biodiversity of these islands across multiple taxonomic groups. At San Ambrosio Island (SA), in Desventuradas, the laminarian kelp (Eisenia cokeri), which is limited to Desventuradas in Chile, accounted for >50% of the benthic cover at wave exposed areas, while more sheltered sites were dominated by sea urchin barrens. The benthos at Robinson Crusoe Island (RC), in the Juan Fernández Archipelago, comprised a diverse mix of macroalgae and invertebrates, a number of which are endemic to the region. The biomass of commercially targeted fishes was >2 times higher in remote sites around RC compared to sheltered locations closest to port, and overall biomass was 35% higher around SA compared to RC, likely reflecting fishing effects around RC. The number of endemic fish species was extremely high at both islands, with 87.5% of the species surveyed at RC and 72% at SA consisting of regional endemics. Remarkably, endemics accounted for 99% of the numerical abundance of fishes surveyed at RC and 96% at SA, which is the highest assemblage-level endemism known for any individual marine ecosystem on earth. Our results highlight the uniqueness and global significance of these biodiversity hotspots exposed to very different fishing pressures.ES received funding from Blancpain, Davidoff Cool Water and The National Geographic Society. Oceana provided funding to ATP. CFG was suported by Grant NC120030 from the Millennium Scientific Initiative.Peer reviewe

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers

Estudio transdisciplinar de la fosa EE1 de la Cova Colomera (Prepirineo de Lleida): implicaciones domésticas y paleoambientales en el Bronce Antiguo del noreste de la Península Ibérica

The transdisciplinary study of the EE1 pit of the Cova Colomera has provided a group of data that can bring some important information about the domestic and economical practices developed in the cave and also about the paleoenvironmental characteristics of this area of the Northeast of the peninsula during the third to second millennia cal. BC. The data show that this cave was used by small groups of people with a mixed farming economy, who also had recourse to mobile activities to complete their diet. Moreover, some structures dug in the floor of the cavity were dug by these groups and went out of use during their short stays in the Cova Colomera. The functionality of these structures is discussed in this article. They could have used them to store surpluses and later to contain refuse or to remove the domestic waste.El estudio transdisciplinar de la fosa EE1 de la Cova Colomera ha proporcionado un conjunto de datos que aportan importante información sobre las prácticas domésticas y económicas desarrolladas en ella, y sobre las características paleoambientales de esta zona del noreste peninsular en el tránsito III-II milenio cal. AC. Los resultados apuntan a que esta cueva fue ocupada por grupos reducidos, con una economía mixta agropecuaria, que recurrían también a actividades cinegéticas para completar su dieta. En sus cortas estancias en la Cova Colomera, crearon y amortizaron estructuras excavadas en el suelo de la cavidad, como la fosa EE1, bien para almacenar excedentes y después desechar basura, o bien para eliminar residuos de origen doméstico

Study of breast cancer incidence in patients of lymphangioleiomyomatosis

The online version of this article (doi:10.1007/s10549-016-3737-8) contains supplementary material, which is available to authorized user

Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM

Ассоциативно-семантическая группа как языковая основа концепта

Статья посвящена описанию особой лексико-семантической парадигмы ассоциативно-семантической группы, которая является частью ассоциативно- семантического комплекса и рассматривается как языковая основа концепта. Исследование проведено с применением описательного, структурного и функционального методов.Статтю присвячено опису особливої лексико-семантичної парадигми асоціативно-семантичної групи, яка є частиною асоціативно-семантичного комплексу і являє собою мовну основу концепту. Дослідження проведено із застосуванням описового, структурного та функціонального методів.The particular lexico-semantic paradigm – associative-semantic group (ASG) which is the part of associative-semantic complex (ASC) – is investigated in the article as a linguistic base of concept. Descriptive, structural, and functional methods were used

¿Murosafuera? locura y desmanicomialización desde el enfoque de derechos humanos. contextualización y análisis de la ley provincial nº 9848 de “protección de la salud mental” promulgada en córdoba el 5 de noviembre de 2010.

El proyecto de investigación se propone el análisis de la Ley 9848 de “Protección de Salud Mental” promulgada en la Provincia de Córdoba a fines del 2010. En ese sentido, se aborda el enfoque de derechos humanos y su contribución al nuevo paradigma de salud mental presente en esa Ley; así como también el movimiento de desmanicomialización, en cuanto anclaje teórico de la misma. Todo lo anterior con el objetivo central de revisar la currícula de la formación de grado de la carrera de psicología en la Facultad de Filosofía y Humanidades de la Universidad Católica de Córdoba, a fin de proponer las transformaciones pertinentes y la posibilidad de una presencia transversal y como contenido específico de esta Ley en ese plan de carrera; toda vez que la hipótesis de trabajo formulada anticipa su ausencia y postula que sólo mediante esta imbricación entre la nueva Ley y la currícula de los alumnos, se logrará formar profesionales capaces de comprender y actuar en base a las profundas implicancias de esta normativa en la práctica profesional de la salud pública. Para propender al cumplimiento de ese propósito, el proyecto examina las concepciones teóricas sobre los procesos de salud-enfermedad; la evolución histórica de la política social sobre salud mental en Argentina; las experiencias nacionales e internacionales de desmanicomialización, y sistematiza los aportes teóricos de Michel Foucault sobre la locura, que sirven de sustento teórico al movimiento social de desmanicomialización.Fil: Ibaña, Griselda Beatriz. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; ArgentinaFil: Padvalskis Simkuz, María Cecilia. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Petit, María Cecilia. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Díaz, Ana Carolina. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; Argentin

¿Murosafuera? locura y desmanicomialización desde el enfoque de derechos humanos. contextualización y análisis de la ley provincial nº 9848 de “protección de la salud mental” promulgada en córdoba el 5 de noviembre de 2010.

El proyecto de investigación se propone el análisis de la Ley 9848 de “Protección de Salud Mental” promulgada en la Provincia de Córdoba a fines del 2010. En ese sentido, se aborda el enfoque de derechos humanos y su contribución al nuevo paradigma de salud mental presente en esa Ley; así como también el movimiento de desmanicomialización, en cuanto anclaje teórico de la misma. Todo lo anterior con el objetivo central de revisar la currícula de la formación de grado de la carrera de psicología en la Facultad de Filosofía y Humanidades de la Universidad Católica de Córdoba, a fin de proponer las transformaciones pertinentes y la posibilidad de una presencia transversal y como contenido específico de esta Ley en ese plan de carrera; toda vez que la hipótesis de trabajo formulada anticipa su ausencia y postula que sólo mediante esta imbricación entre la nueva Ley y la currícula de los alumnos, se logrará formar profesionales capaces de comprender y actuar en base a las profundas implicancias de esta normativa en la práctica profesional de la salud pública. Para propender al cumplimiento de ese propósito, el proyecto examina las concepciones teóricas sobre los procesos de salud-enfermedad; la evolución histórica de la política social sobre salud mental en Argentina; las experiencias nacionales e internacionales de desmanicomialización, y sistematiza los aportes teóricos de Michel Foucault sobre la locura, que sirven de sustento teórico al movimiento social de desmanicomialización.Fil: Ibaña, Griselda Beatriz. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; ArgentinaFil: Padvalskis Simkuz, María Cecilia. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Petit, María Cecilia. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Díaz, Ana Carolina. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; Argentin

Mountain strongholds for woody angiosperms during the Late Pleistocene in SE Iberia

Mediterranean mountains played an essential role during glacial periods as vegetation refugia. The SE Iberia Late Pleistocene woody angiosperm fossil and floristic evidences are reviewed in the context of phylogeographical studies aiming to identify (i) spatial patterns related to woody angiosperms glacial survival, (ii) structural and functional characteristics of montane refugia, and (iii) gaps in knowledge on the woody angiosperm patterns of survival in Mediterranean mountains. The distribution of palaeobotanical data for SE Iberia refugia has been found to be taphonomically biased due to the scarcity of available and/or studied high-altitude Late Pleistocene sites. However, Siles Lake data together with floristic inference provide evidences for woody angiosperms’ survival in a high-altitude Mediterranean area. The main features boosting survival at montane contexts are physiographic complexity and water availability. Phylogeography studies have mainly been conducted at a continental scale. Although they cohere with palaeobotanical data to a broad scale, a general lack of sampling of SE Iberian range-edge populations, as well as misconceptions about the origin of the populations sampled, impede to infer the proper location of woody angiosperms’ mountain refugia and their importance in the post-glacial European colonisation. We conclude that floristic, geobotanical, palaeobotanical, ethnographical and genetic evidence should be merged to gain a deeper understanding on the role played by Mediterranean mountains as glacial refugia in order to explain the current distribution of many plants and the large biodiversity levels encountered in Mediterranean mountain areas. This is hallmark for effective and efficient conservation and management