Coalition for Health and Gender Equity (CHANGE)-a protocol for a global cross-sectional survey of health and gender equity in rheumatology.

Objectives: The primary aim of the CHANGE survey is to determine the current state of gender equity within rheumatology, and secondarily, to review the physician perspective on bullying, harassment and equipoise of opportunities within rheumatology. Methods: The CHANGE e-survey is a cross-sectional self-reported questionnaire adapted from EULAR's gender equity in academic rheumatology task force. The survey was launched in January 2023; it is available in six languages and distributed widely via rheumatology organizations and social media. Eligible participants include rheumatologist physicians and rheumatology health-care professionals. Survey responses will undergo descriptive analysis and inter-group comparison aiming to explore gender-based discrimination using logistic regression, with subgroup analyses for country/continent variations. Conclusion: This e-survey represents a comprehensive global initiative led by an international consortium, aimed at exploring and investigating the gender-related disparities and obstacles encountered by rheumatologists and rheumatology health-care professionals across diverse communities and health-care environments. By pursuing this initiative, we aim to take the broader rheumatology community a step closer to understanding the underlying origins of inequities and their determinants. Such insights are pivotal in identifying viable interventions and strategies to foster gender equity within the field. Ultimately, our collective objective is to ensure equitable access to opportunities for every individual, irrespective of gender, thereby promoting inclusivity and fairness across the entire spectrum of professional practice and career development.

Surviving in a multistressor world: Gene expression changes in earthworms exposed to heat, desiccation, and chemicals.

An investigation of the effects of anthropogenic stress on terrestrial ecosystems is urgently needed. In this work, we explored how exposure to heat, desiccation, and chemical stress alters the expression of genes that encode heat shock proteins (HSPs), an enzyme that responds to oxidative stress (CAT), hypoxia-related proteins (HIF1 and HYOU), and a DNA repair-related protein (PARP1) in the earthworm Eisenia fetida. Exposure to heat (31°C) for 24 h upregulated HSPs and hypoxia-related genes, suggesting possible acquired thermotolerance. Desiccation showed a similar expression profile; however, the HSP response was activated to a lesser extent. Heat and desiccation activated the small HSP at 24 h, suggesting that they may play a role in adaptation. Simultaneous exposure to endosulfan and temperature for 7 h upregulated all of the evaluated genes, implicating a coordinated response involving multiple biological processes to ensure survival and acclimation. These results highlight the relevance of multistress analysis in terrestrial invertebrates.

C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity.

The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons.

Committed (dis)honesty: A systematic meta-analytic review of the divergent effects of social commitment to individuals or honesty oaths on dishonest behavior.

People feel committed to other individuals, groups, organizations, or moral norms in many contexts of everyday life. Such social commitment can lead to positive outcomes, such as increased job satisfaction or relationship longevity; yet, there can also be detrimental effects to feeling committed. Recent high-profile cases of fraud or corruption in companies like Enron or Volkswagen are likely influenced by strong commitment to the organization or coworkers. Although social commitment might increase dishonest behavior, there is little systematic knowledge about when and how this may occur. In the present project, we reviewed 20,988 articles, focusing on studies that experimentally manipulated social commitment and measured dishonest behavior. We retained 445 effect sizes from 121 articles featuring a total of 91,683 participants across 33 countries. We found no evidence that social commitment increases or reduces dishonest behavior in general. Nonetheless, we did find evidence that the effect strongly depends on the target of the commitment. Feeling committed to other individuals or groups reduces honest behavior (g = -0.17 [-0.24, -0.11]), whereas feeling committed to honesty norms through honesty oaths or pledges increases honest behavior (g = 0.27 [0.19, 0.36]). The analysis identified several moderating variables and detected some degree of publication bias across effects. Our findings highlight the diverging effects of different forms of social commitment on dishonest behavior and suggest a combination of the different forms of commitment could be a possible means to combat corruption and dishonest behavior in the organizational context. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Healthcare Professionals' Perceptions about the Implementation of Shared Decision-Making in Primary Care: A Qualitative Study from a Virtual Community of Practice.

Background: The incorporation of shared decision making (SDM) is a central part of empowerment processes, as it facilitates greater activation on the part of patients, increasing the likelihood of them gaining control over their healthcare and developing skills to solve their health problems. Despite these benefits, there are still difficulties in the implementation of SDM among healthcare professionals due to internal and external factors related to the context and health systems. Aim: To explore primary care professionals (PCPs)' perceptions of the SDM model, based on their preconceptions and experience in clinical practice. Methods: A framework analysis was conducted on qualitative data derived from a virtual community practice forum, within a cluster-randomized clinical trial developed in the e-MPODERA project. Results: The most important points in the opinions of the PCPs were: exploring the patients' values, preferences and expectations, providing them with and checking their understanding of up-to-date and evidence-based health information. The analysis revealed three themes: determinants of the implementation process of SDM, lack of consistency and dilemmas and benefits of PCP active listening, motivation and positive expectations of SDM. Discussion: In our initial analysis, we examined the connections between the categories of the TDC model and its application in the primary care context. The categories related to the model reflect the theoretical understanding of professionals, while those related to perceptions of its application and use show certain discrepancies. These discrepancies could indicate a lack of understanding of the model and its real-world implications or insufficient commitment on the part of professionals or the organization to ensure its effective implementation. Conclusions: Specific targeted training that addresses knowledge, attitudes and practice may resolve the aforementioned findings.

Antecedentes: La incorporación de la toma de decisiones compartida (TDC) es una parte central del empoderamiento del paciente, ya que facilita una mayor activación, ganar control sobre la atención que recibe y desarrollar habilidades para resolver sus problemas de salud. A pesar de estos beneficios, todavía existen dificultades para implementar la TDC entre los profesionales sanitarios debido a factores internos de los propios profesionales y externos, relacionados con el contexto y los sistemas sanitarios. Objetivo: Explorar en el foro de una comunidad virtual de práctica (CVdP) las percepciones de los profesionales de atención primaria (PAP) sobre el modelo de TDC en función de sus ideas preconcebidas y su experiencia en la práctica clínica. Métodos: Se realizó un análisis de marco desde un abordaje cualitativo de las intervenciones hechas por los PAP en el foro de una CVdP. Esta CVdP se implementó dentro de un ensayo clínico aleatorizado por grupos desarrollado en el proyecto e-MPODERA. Resultados: Los aspectos más importantes relacionados con la TDC desde la perspectiva de los PAP incluyeron: explorar los valores, preferencias y expectativas de los pacientes, proporcionarles información actualizada y basada en la evidencia, y comprobar su comprensión. En el análisis posterior, tres categorías emergieron como los temas más relevantes: determinantes de la implementación del TDC, falta de consistencia y dilemas, y beneficios de la escucha activa de los PAP, motivación y expectativas positivas de la TDC. Discusión: En nuestro análisis inicial, examinamos las conexiones entre las categorías del modelo de TDC y su aplicación en el contexto de atención primaria. Las categorías relacionadas con el modelo reflejan la comprensión teórica de los profesionales, mientras que las relativas a las percepciones de su aplicación y uso muestran ciertas discrepancias. Estas discrepancias podrían indicar una falta de comprensión del modelo y de sus implicaciones en el mundo real o un compromiso insuficiente por parte de los profesionales o de la organización para garantizar su aplicación efectiva. Conclusión: Una formación específica que aborde los conocimientos, las actitudes y la práctica puede resolver los hallazgos mencionados.

Cuidando al final de la vida. Un programa de intervención online para familiares de pacientes oncológicos en fase paliativa / Caring the caregivers. An online psychological intervention for family caregivers of oncological palliative patients

Resumen: Objetivo: Analizar la eficacia de un programa de intervención psicológica grupal en formato online diseñado para reducir la sobrecarga y el malestar emocional de los cuidadores informales de pacientes oncológicos en fase final de vida. Método: El programa se desarrolló para cuidadores principales de pacientes oncológicos en situación de enfermedad avanzada, con pronóstico de vida inferior a 6 meses. La intervención consistió en cuatro sesiones semanales. Los instrumentos de evaluación fueron la Escala de Detección de Malestar Emocional del Cuidador Principal y la Escala Zarit Reducida y se aplicaron al inicio y al final del programa. Además, se categorizaron las principales preocupaciones de los cuidadores a través de la Escala de Detección del Malestar del Cuidador Principal. Se utilizaron estadísticos descriptivos y t de Student. Resultados: En el estudio participaron 38 familiares de los cuales el 81,6% eran mujeres. En cuanto el grado de parentesco, el 44,7% eran descendientes del paciente. El malestar emocional se redujo significativamente después de la intervención. La incertidumbre se mantuvo como principal preocupación en ambos momentos de medida. Antes del programa, la segunda preocupación más frecuente fue el sufrimiento por el ser querido enfermo, mientras que después de la intervención fue la preocupación por el sufrimiento de otros miembros de la familia. Conclusiones: La realización de este programa de intervención psicológica grupal online demostró ser efectiva para reducir el malestar emocional en los cuidadores principales de pacientes oncológicos al final de la vida. La incertidumbre fue una preocupación constante a lo largo del programa en los familiares. (AU)

Abstract:Aim: analyze the effectiveness of an online delivered psychological intervention program for oncological palliative caregivers in order to reduce the distress and caregiver burden. Methods: The program was developed for primary caregivers of advanced cancer patients, with a life expectancy of less than 6 months. The intervention consisted of 4 weekly sessions. The assessment instruments were the Caregiver Emotional Distress Detection Scale and the Zarit’s Reduced Scale and were applied at the beginning and end of the program. In addition, the main worries of the caregivers were categorized by the Caregiver Emotional Distress Detection Scale. Descriptive statistics and Student’s t were used. Results: 38 caregivers enrolled in intervention, 81.6% of whom were women. Regarding the degree of kinship, 44.7% were descendants of the patient. The distress was significantly reduced after the intervention. Uncertainty remained the main worry at both moments of measurement. Before the program, the second most frequent worry was the suffering of the patient, while after the intervention it was worries about the suffering of other family members. Conclusions: Carrying out this online group psychological intervention program proved to be effective in reducing emotional distress in the main caregivers of cancer patients at the end of life. Uncertainty was a constant concern throughout the program in the relatives. (AU)

Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG / Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study

Introducción: Los programas de optimización de antimicrobianos (PROA) son herramientas clave en la adecuación de estos fármacos. La información disponible sobre la aplicación e indicadores para monitorizar estos programas en urgencias es limitada. El objetivo del estudio es conocer el grado de implantación de programas PROA en los servicios de urgencias, así como el uso de antimicrobianos en estas unidades. Material y métodos. Estudio multicéntrico retrospectivo. Se envió una invitación a todos los participantes del grupo de trabajo de farmacéuticos de urgencias REDFASTER-SEFH. Se utilizó un cuestionario de 21 ítems, contestado por un equipo formado por especialistas en los servicios de farmacia hospitalaria, urgencias, enfermedades infecciosas y microbiología. Resultados. 18 hospitales completaron la encuesta. Catorce (77,8%) disponían de un responsable PROA en la unidad. El valor de DDD por 1000 ingresos osciló entre 36,5 y 400,5 (mediana 100,4 [RIQ:57,2-157,3]). El grupo de carbapenémicos y macrólidos presentó una amplia variabilidad. Únicamente seis (33,3%) hospitales disponían de informe anual de resistencias específico para urocultivos y hemocultivos en urgencias. El porcentaje de multirresistentes en urocultivos fue del 12,5% y en hemocultivos del 12,2%. El porcentaje de adecuación en bacteremia de acuerdo con el resultado del hemocultivo fue del 81,0% (RIQ:74,6-85,0%), y en infección urinaria del 78,0% (RIQ:71,5-88,0%). Conclusiones. Pese a la existencia de responsables PROA, actividades formativas y guías de tratamiento en urgencias, la información sobre el uso de antimicrobianos y el perfil de resistencias en estas unidades es limitado. Futuras actividades han de ir encaminadas a mejorar la información sobre los resultados PROA propios para estas unidades. (AU)

Introduction: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know theextent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. Material and methods. Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. Results. Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). Conclusions: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units. (AU)

Interpersonal protective factors for LGBTQ+ youth at multiple intersecting social identities and positions.

Interpersonal supports are protective against multiple negative health outcomes for youth such as emotional distress and substance use. However, finding interpersonal support may be difficult for youth exposed to intersecting racism, heterosexism, and cisgenderism, who may feel they are "outsiders within" their multiple communities. This study explores disparities in interpersonal supports for youth at different sociodemographic intersections. The 2019 Minnesota Student Survey includes data from 80,456 high school students, including measures of four interpersonal supports: feeling cared about by parents, other adult relatives, friends, and community adults. Exhaustive Chi-square Automatic Interaction Detection analysis was used to examine all interactions among four social identities/positions (racialized/ethnic identity, sexual identity, gender identity, sex assigned at birth) to identify groups who report different rates of caring from each source (Bonferroni adjusted p<.05). In the overall sample, 69.24% perceived the highest level of caring ("very much") from parents, 50.09% from other adult relatives, 39.94% from friends, and 15.03% from community adults. Models identified considerable differences in each source of support. For example, more than 72% of straight, cisgender youth reported their parents cared about them very much, but youth who identified as LGBQ and TGD or gender-questioning were much less likely to report high parent caring (less than 36%) across multiple racialized/ethnic identities and regardless of sex assigned at birth. Findings highlight the importance of better understanding the ways interpersonal support might differ across groups, and underscore a need for intersectionality-tailored interventions to develop protective interpersonal supports for LGBTQ+ youth, rather than one-size-fits-all approaches.

Optical and Electrochemical Properties of a Nanostructured ZnO Thin Layer Deposited on a Nanoporous Alumina Structure via Atomic Layer Deposition.

This study explores the optical and electrochemical properties of a ZnO coating layer deposited on a nanoporous alumina structure (NPAS) for potential multifunctional applications. The NPAS, synthesized through an electrochemical anodization process, displays well-defined nanochannels with a high aspect ratio (~3000). The ZnO coating, achieved via atomic layer deposition, enables the tuning of the pore diameter and porosity of the NPAS, thereby influencing both the optical and electrochemical interfacial properties. A comprehensive characterization using photoluminescence, spectroscopy ellipsometry and impedance spectroscopy (with the sample in contact with NaCl solutions) provides insights into optical and electrochemical parameters, including the refractive index, absorption coefficient, and electrolyte-ZnO/NPAS interface processes. This research demonstrates potential for tailoring the optical and interfacial properties of nanoporous structures by selecting appropriate coating materials, thus opening avenues for their utilization in various technological applications.

Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.

Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a's function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Occurrence of Pseudomonas syringae pvs. actinidiae, actinidifoliorum and Other P. syringae Strains on Kiwifruit in Northern Spain.

Pseudomonas syringae pv. actinidiae (Psa), the agent causing bacterial canker of kiwifruit, has been present in the Principality of Asturias (PA), Northern Spain, since 2013, although with restricted distribution. In this study, 53 strains collected in kiwifruit orchards in PA during the period 2014-2020 were characterized by a polyphasic approach including biochemical and phylogenetic analysis. Thirty-three strains, previously identified by PCR as Psa, have been found to be a homogeneous group in phylogenetic analysis, which seems to indicate that there have been few introductions of the pathogen into the region. Two strains were confirmed as P. syringae pv. actinidifoliorum (Pfm), so this is the first report of Pfm in the PA. The remaining 18 strains were found to be close to P. avellanae and P. syringae pv. antirrhini or to strains described as Pfm look-alikes. Pathogenicity tests carried out on peppers with a selection of strains have shown that both Psa and Pfm caused clear damage, while the 18 atypical strains caused variable lesions. It would be necessary to carry out pathogenicity testing of atypical strains on kiwifruit plants to study the role of these strains in the kiwifruit pathosystem to evaluate their pathogenic potential in this crop.

Exploring floral morphoanatomy and embryology in wild populations of Chrysolaena flexuosa (Vernonia, Asteraceae): a contribution to understanding its ornamental potential.

Chrysolaena flexuosa (Sims.) H. Rob. is a South American species in the tribe Vernonieae, with potential ornamental value: it has attractive inflorescences, is suitable for pot cultivation, and its cypselae are useful for dried flower arrangements. Apart from studies on the growth dynamics of this species under cultivation, chromosome number, DNA content, ploidy level, size, pollen viability, and the characterization of phenotypic and genetic variability, it is noteworthy that other aspects regarding the floral architecture, reproductive mode, and gametophyte formation of C. flexuosa have not yet been studied. For this reason, our study encompasses a floral morphoanatomical survey and a comprehensive assessment of gametophyte development in the species. As a result of this study, we report new floral morphotypes, confirming that the morphological variability of the species might be greater than speculated. The morphoanatomy of the androecium and gynoecium and the male and female gametophyte developmental characteristics are uniform in all the populations studied despite the different ploidy levels. Chrysolaena flexuosa has five tetrasporangiate stamens of the dicotyledonous type of development; all the populations studied displayed a unilocular inferior ovary with a single anatropous, unitegumented, and tenuinucellar ovule. Given that all the embryo sacs observed were of the Polygonum-type development regardless of the ploidy level, we infer that the populations analyzed are fertile and undergo sexual reproduction. Our results not only contribute further research in the field of breeding systems and propagation of this species, but also promote the successful introduction of C. flexuosa to the plant ornamental market.

Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study.

Background: Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods: This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results: A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p<0.001), percentage predicted forced vital capacity (HR 0.96; p=0.001), lymphocytosis in bronchoalveolar lavage (BAL) (HR 0.93; p=0.001), presence of acute exacerbation during follow-up (HR 3.04; p=0.001) and GAP (gender, age and lung physiology) index (HR 1.96; p<0.01). In the group of biopsied patients, the presence of fibroblastic foci at biopsy (HR 8.39; p<0.001) stands out in multivariate Cox regression analyses as a highly significant predictor for increased mortality or lung transplant. GAP index (HR 1.26; p=0.009), lymphocytosis in BAL (HR 0.97; p=0.018) and age (HR 1.03; p=0.018) are also predictors of progression. Conclusions: The study identified several prognostic factors for progression and/or survival in fHP. The presence of fibroblastic foci at biopsy was a consistent predictor for increased mortality and the presence of lymphocytosis in BAL was inversely related to mortality.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Medical deserts in Spain-Insights from an international project.

INTRODUCTION: Medical deserts are a growing phenomenon across many European countries. They are usually defined as (i) rural areas, (ii) underserved areas or (iii) by applying a measure of distance/time to a facility or a combination of the three characteristics. The objective was to define medical deserts in Spain as well as map their driving factors and approaches to mitigate them. METHODS: A mixed methods approach was applied following the project "A Roadmap out of medical deserts into supportive health workforce initiatives and policies" work plan. It included the following elements: (i) a scoping literature review; (ii) a questionnaire survey; (iii) national stakeholders' workshop; (iv) a descriptive case study on medical deserts in Spain. RESULTS: Medical deserts in Spain exist in the form of mostly rural areas with limited access to health care. The main challenge in their identification and monitoring is local data availability. Diversity of both factors contributing to medical deserts and solutions applied to eliminate or mitigate them can be identified in Spain. They can be related to demand for or supply of health care services. More national data, analyses and/or initiatives seem to be focused on the health care supply dimension. CONCLUSIONS: Addressing medical deserts in Spain requires a comprehensive and multidimensional approach. Effective policies are needed to address both the medical staff education and planning system, working conditions, as well as more intersectoral approach to the population health management.

Preclinical characterization of a non-peptidomimetic HIV protease inhibitor with improved metabolic stability.

Protease inhibitors (PIs) remain an important component of antiretroviral therapy for the treatment of HIV-1 infection due to their high genetic barrier to resistance development. Nevertheless, the two most commonly prescribed HIV PIs, atazanavir and darunavir, still require co-administration with a pharmacokinetic boosting agent to maintain sufficient drug plasma levels which can lead to undesirable drug-drug interactions. Herein, we describe GS-9770, a novel investigational non-peptidomimetic HIV PI with unboosted once-daily oral dosing potential due to improvements in its metabolic stability and its pharmacokinetic properties in preclinical animal species. This compound demonstrates potent inhibitory activity and high on-target selectivity for recombinant HIV-1 protease versus other aspartic proteases tested. In cell culture, GS-9770 inhibits Gag polyprotein cleavage and shows nanomolar anti-HIV-1 potency in primary human cells permissive to HIV-1 infection and against a broad range of HIV subtypes. GS-9770 demonstrates an improved resistance profile against a panel of patient-derived HIV-1 isolates with resistance to atazanavir and darunavir. In resistance selection experiments, GS-9770 prevented the emergence of breakthrough HIV-1 variants at all fixed drug concentrations tested and required multiple protease substitutions to enable outgrowth of virus exposed to escalating concentrations of GS-9770. This compound also remained fully active against viruses resistant to drugs from other antiviral classes and showed no in vitro antagonism when combined pairwise with drugs from other antiretroviral classes. Collectively, these preclinical data identify GS-9770 as a potent, non-peptidomimetic once-daily oral HIV PI with potential to overcome the persistent requirement for pharmacological boosting with this class of antiretroviral agents.