Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial.

INTRODUCTION: Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. METHODS AND ANALYSIS: People aged 30-60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. TRIAL REGISTRATION NUMBER: NCT06046326.

Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.

A systematic review and a comprehensive approach to PhD students' wellbeing.

The pursuit of a doctoral degree is a challenging process that can have a negative impact on the wellbeing of PhD students. Therefore, the aim here is to offer a systematic review of the current state of the literature on wellbeing among PhD students and the variables it involves in order to build an integrative model that will enrich future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology for systematic reviews has been used to lay out the process in a flow diagram. We systematically review studies up to 2021 (N = 38) published on the Web of Science and SCOPUS databases. The results show the current state of the literature on wellbeing in PhD students, the characteristics of the studies (location, study design, and sample), how the literature defines the concept, the variables involved, the study limitations, and future perspectives to improve the quality of life of doctoral students. Finally, a comprehensive approach to the topic is presented in an integrative model that encompasses all variables identified in the literature and offers a guide for future research.

Shipwrecked on the Rock, or Not Quite: Gypsophytes and Edaphic Islands.

Species-area relationships (SAR) constitute a key aspect of ecological theory and are integral to other scientific disciplines, such as biogeography, which have played a crucial role in advancing biology. The theory of insular biogeography provides a clear example. This theory initially expanded from true islands to other types of systems characterized by their insularity. One such approach was linked to geoedaphic islands, as seen in gypsum outcrops. While these continental areas have been considered insular systems, only limited and mostly indirect evidence thereof has been provided. This study utilized SAR to advance the understanding of gypsum outcrops as insular continental territories. It is hereby hypothesized that gypsum outcrops are edaphic islands, although their insular nature depends on the different functional or ecological plant types, and this nature will be reflected in the potential Arrhenius model z values. The results obtained support both hypotheses and provide insight into the ecological factors that help interpret the insularity of these areas. This interpretation goes beyond their mere extent and the distance among outcrops, emphasizing the importance of environmental filters. Said filters vary in permeability depending on the degree of gypsophily, or preference for gypsum, exhibited by different species.

Spiritual well-being, faith, meaning in life, peace, and purpose in life for cancer-related fatigue: systematic review with meta-analysis and meta-regressions.

BACKGROUND: Cancer-related fatigue is associated with spiritual distress. Spiritual well-being, characterized by the presence of factors such as meaning in life or purpose in life, seems to play an important role in the management of symptoms of cancer. Currently, the number of studies evaluating the association between cancer-related fatigue and spiritual well-being is increasing and no systematic review has been conducted. AIM: To summarize the association between cancer-related fatigue and spiritual well-being, faith, meaning in life, peace, and purpose in life. DESIGN: A systematic review with meta-analysis. DATA SOURCES: The CINAHL, Embase, PsycINFO, and PubMed databases were searched from inception to 9 October 2023. We considered studies evaluating the cross-sectional or longitudinal association between cancer-related fatigue and the spiritual factors above mentioned. The Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool assessed the methodological quality of cross-sectional and longitudinal studies, respectively. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system rated the certainty of evidence. Meta-analyses, meta-regressions, subgroup meta-analyses, and sensitivity analyses were conducted. RESULTS: A total of 13 studies were included and no longitudinal findings were found. One meta-analysis showed that cancer-related fatigue may be negatively correlated with spiritual well-being (r = - 0.37 (95%CI - 0.44 to - 0.28) p < 0.01). In addition, another meta-analysis found the correlation between cancer-related fatigue and faith was not statistically significant (r = - 0.25 (95%CI - 0.66 to 0.28) p = 0.36). CONCLUSIONS: Cancer-related fatigue may be correlated with spiritual well-being. However, the certainty of evidence was very low across the meta-analyzed outcomes. IMPLICATIONS FOR CANCER SURVIVORS: A negative correlation was observed between spiritual well-being and cancer-related fatigue.

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

How can clinicians enhance self-efficacy beliefs in osteoarthritis? An overview of systematic reviews with meta-analysis.

This overview of reviews aimed to synthesize the effectiveness of non-pharmacological approaches to enhance self-efficacy in people with osteoarthritis. The CINAHL, Embase, PsycINFO, PubMed, SPORTDiscus, and the Cochrane Library databases were searched from inception to December 2023. We considered systematic reviews with meta-analysis of randomized clinical trials evaluating any non-pharmacological intervention. We used AMSTAR 2 to assess the methodological quality of reviews. The overlap between reviews was calculated. We included eight systematic reviews with meta-analysis evaluating 30 different clinical trials. Overall, mind-body exercises, psychological interventions, and self-management strategies may improve arthritis self-efficacy. Specifically, the meta-analyses showed tai chi exercises, coping skills training, and the arthritis self-management program are more effective than controls to enhance arthritis self-efficacy in people with hip and/or knee osteoarthritis. In addition, inconsistent results were detected across meta-analyses regarding the effectiveness of multidisciplinary interventions. Finally, the degree of overlap between all reviews was moderate (CCA = 6%) and many included reviews reported most of the items of AMSTAR 2. Tai chi exercises, coping skills training, and the arthritis self-management program may be beneficial for enhancing arthritis self-efficacy. Open Science Framework Registration: https://doi.org/10.17605/OSF.IO/VX2T6 .

The prevalence of anxiety and depression in cancer around the world: An overview of systematic reviews evaluating 128 meta-analyses.

BACKGROUND: This overview of systematic reviews with meta-analysis summarized the prevalence of anxiety and depression in different types of tumors around the world. METHODS: The quality of reviews was assessed. The degree of overlap between reviews was calculated. The regional prevalence of anxiety and depression was shown in the main text based on the World Health Organization regions. RESULTS: Twenty-five reviews including 128 meta-analyses of interest were selected. The pooled prevalence of anxiety in breast tumors was in Africa (19 %), the Americas (38 %), Eastern Mediterranean (56 %), Europe (38 %), South-East Asia (42 %), and Western Pacific (26 %). The pooled prevalence of depression in breast tumors was in Africa (40 %), the Americas (23-25 %), Eastern Mediterranean (49-51 %), Europe (27-29 %), South-East Asia (23-33 %), Western Pacific (29 %). The pooled prevalence of depression in digestive tumors was in the Americas (4-44 %), Eastern Mediterranean (42 %), Europe (20-27 %), South-East Asia (66 %), and Western Pacific (24-40 %). The pooled national prevalence of anxiety and depression was mainly evaluated in China and Iran. LIMITATIONS: Important methodological issues were identified. For example, no reviews judged the certainty of evidence. CONCLUSIONS: The Eastern Mediterranean region showed the highest prevalence of anxiety and depression for breast tumors. The South-East Asian region showed the highest prevalence of depression for digestive tumors. In these regions, many countries are considered low-income and middle-income countries. Further research funding would help increase the investigation on this topic, which may allow the development of preventive strategies that reduce the prevalence of anxiety and depression.

Evaluation of selected natural sesquiterpenes as sensitizing agents of ß-lactam-resistant bacterial strains.

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.

Tailoring evidence into action: using a codesign approach for biodiversity information in the Tropical Andes / Toma de decisiones basadas en la evidencia: un enfoque de codiseño para la información sobre biodiversidad en los Andes tropicales / Tomada de decisão baseada em evidências: uma abordagem de co-design para informações sobre biodiversidade nos Andes tropicais

Biodiversity conservation is a complex and transdisciplinary problem that requires engagement and cooperation among scientific, societal, economic, and political institutions. However, historical approaches have often failed to bring together and address the needs of all relevant stakeholders in decision­making processes. The Tropical Andes, a biodiversity hotspot where conservation efforts often conflict with socioeconomic issues and policies that prioritize economic development, provides an ideal model to develop and implement more effective approaches. In this study, we present a co­design approach that mainstreams and improves the flow of biodiversity information in the Tropical Andes, while creating tailored outputs that meet the needs of economic and societal stakeholders. We employed a consultative process that brought together biodiversity information users and producers at the local, national, and regional levels through a combination of surveys and workshops. This approach identified priority needs and limitations of the flow of biodiversity information in the region, which led to the co­design of user­relevant biodiversity indicators. By leveraging the existing capacities of biodiversity information users and producers, we were able to co­design multiple biodiversity indicators and prioritize two for full implementation ensuring that the data was findable, accessible, interoperable, and reusable based on the FAIR principles. This approach helped address limitations that were identified in the stakeholder engagement process, including gaps in data availability and the need for more accessible biodiversity information. Additionally, capacity­building workshops were incorporated for all producers of biodiversity information involved, which aimed to not only improve the current flow of biodiversity information in the region but also facilitate its future sustainability. Our approach can serve as a valuable blueprint for mainstreaming biodiversity information and making it more inclusive in the future, especially considering the diverse worldviews, values, and knowledge systems between science, policy, and practice.

La conservación de la biodiversidad es un problema complejo y transdisciplinario que requiere el compromiso y la cooperación entre instituciones científicas, sociales, económicas y políticas. Sin embargo, los enfoques tradicionales/convencionales  a menudo no logran  reunir y abordar las necesidades de todos los actores relevantes en los procesos de toma de decisiones. Los Andes tropicales, un área clave  de biodiversidad donde los esfuerzos de conservación a menudo entran en conflicto con cuestiones socioeconómicas y políticas que priorizan el desarrollo económico, proporcionan un modelo ideal para desarrollar e implementar enfoques más efectivos. En este estudio, presentamos un enfoque co-diseño que integra y mejora el flujo de información sobre biodiversidad en los Andes tropicales, creando resultados personalizados que satisfacen las necesidades, tanto económicas como sociales, de las partes interesadas. Empleamos un proceso de consulta que reunió a usuarios y productores de información sobre biodiversidad a nivel local, nacional y regional, a través de encuestas y talleres. Este enfoque ha permitido identificar necesidades prioritarias y limitaciones del flujo de información sobre biodiversidad en la región; lo cual llevó al codiseño de indicadores de biodiversidad relevantes para los usuarios. Aprovechando las capacidades existentes de los usuarios y productores de información sobre biodiversidad, pudimos co-diseñar múltiples indicadores de biodiversidad y priorizar dos de estos para su implementación completa, asegurando que los datos sean localizables, accesibles, interoperables y reutilizables, según los principios FAIR. Este enfoque ayudó a abordar las limitaciones que se identificaron en el proceso de participación de las partes interesadas; incluidas las brechas en la disponibilidad de datos y la necesidad de información sobre biodiversidad más accesible. Además, se incorporaron talleres de desarrollo de capacidades para todos los productores de información sobre biodiversidad involucrados, los cuales apuntaron no sólo a mejorar el flujo actual de información sobre biodiversidad en la región, sino también facilitar su sostenibilidad futura. Nuestro enfoque puede servir como un modelo valioso para incorporar la información sobre biodiversidad y hacerla más inclusiva en el futuro; especialmente si consideramos las diversas perspectivas globales, valores y sistemas de conocimiento implicados en las interacciones entre  la ciencia, la política y su aplicación práctica.

A conservação da biodiversidade é um problema complexo e transdisciplinar que requer compromisso e cooperação entre instituições científicas, sociais, económicas e políticas. No entanto, as abordagens tradicionais/convencionais muitas vezes não conseguem reunir e responder às necessidades de todos os intervenientes relevantes nos processos de tomada de decisão. Os Andes tropicais, uma área chave para a biodiversidade onde os esforços de conservação entram frequentemente em conflito com questões socioeconómicas e políticas que dão prioridade ao desenvolvimento económico, fornecem um modelo ideal para desenvolver e implementar abordagens mais eficazes. Neste estudo, apresentamos uma abordagem de co-design que integra e melhora o fluxo de informações sobre biodiversidade nos Andes tropicais, criando resultados personalizados que atendem às necessidades, tanto econômicas quanto sociais, das partes interessadas. Empregamos um processo de consulta que reuniu usuários e produtores de informações sobre biodiversidade nos níveis local, nacional e regional, por meio de pesquisas e workshops. Esta abordagem permitiu identificar necessidades prioritárias e limitações do fluxo de informação sobre a biodiversidade na região; o que levou à concepção conjunta de indicadores de biodiversidade relevantes para os utilizadores. Aproveitando as capacidades existentes dos utilizadores e produtores de informação sobre biodiversidade, fomos capazes de conceber em conjunto vários indicadores de biodiversidade e priorizar dois deles para implementação total, garantindo que os dados sejam localizáveis, acessíveis, interoperáveis ​​e reutilizáveis, de acordo com os princípios FAIR. Esta abordagem ajudou a resolver as limitações identificadas no processo de envolvimento das partes interessadas; incluindo lacunas na disponibilidade de dados e a necessidade de informações mais acessíveis sobre biodiversidade. Além disso, foram incorporados workshops de capacitação para todos os produtores de informação sobre biodiversidade envolvidos, que visaram não só melhorar o fluxo actual de informação sobre biodiversidade na região, mas também facilitar a sua sustentabilidade futura. A nossa abordagem pode servir como um modelo valioso para incorporar informações sobre biodiversidade e torná-las mais inclusivas no futuro; especialmente se considerarmos as diversas perspectivas globais, valores e sistemas de conhecimento envolvidos nas interações entre ciência, política e sua aplicação prática.

Effective Coping with Academic Stress Is a Matter of Personality Types: Revisiting the Person-Centred Approach.

Recent literature provides alarming data on the increase in university academic stress. The role of personality in understanding and addressing this problem is well established. However, this evidence could be improved by adopting a person-centred approach (e.g., types), as opposed to the usual variable-centred approach (e.g., traits), and considering the role of gender. Our aim was to explore how personality types and gender relate to coping strategies and perceived coping efficacy for academic stress. A total of 810 university psychology students completed the NEO-FFI Inventory and the Coping Strategies Inventory. Post hoc tests for MANOVA and ANOVA were performed. Types and gender were used as predictors and coping strategies, and perceived coping efficacy as criteria. There was no type-gender interaction. Types combining low neuroticism-high conscientiousness (e.g., entrepreneur) chose the most adaptive coping strategies and showed the highest levels of perceived coping efficacy, while high neuroticism-low conscientiousness types (e.g., insecure) opted for maladaptive coping strategies and presented the lowest perceived coping efficacy. Gender was not associated with perceived coping efficacy but with use (e.g., women prefer emotional expression). The personality typology provided useful information on individual differences in coping with academic stress, which can help guide specific strategies to manage it.

Psychological and spiritual interventions to enhance meaning in adults diagnosed with cancer: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To summarize the evidence on the effectiveness that psychological and/or spiritual interventions may have to change the levels of meaning, measured with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), in adults diagnosed with cancer. METHODS: Systematic review with meta-analysis and meta-regression. CINAHL (via EBSCOhost), Embase, PubMed, PsycINFO (via ProQuest), and the Cochrane Library were searched from inception to 21st October 2022. Manual searches were conducted. Only randomized clinical trials (RCTs) were included. The risk of bias was assessed with the Cochrane Risk of Bias tool 2. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to judge the certainty of the evidence. RESULTS: Eight RCTs were included (N = 1682). Although some individual studies showed positive effects to enhance meaning using mindfulness or dignity therapy, the overall and individual meta-analyses showed a lack of effect of psychological and spiritual interventions in comparison to comparator interventions (MD (95%CI) = -0.19 (-0.45 to 0.06), p = 0.11, Tau2 = 0.0015, I2 = 2%). Publication bias was undetected (Egger's test = 0.35). Furthermore, no RCTs were judged to have a low risk of bias and the overall certainty of the evidence was judged as low. Meta-regression and subgroups meta-analyses also found possible sources of heterogeneity such as some cancer characteristics, the educational stage, or the religious affiliation. CONCLUSIONS: Despite some RCTs may show promising results following mindfulness or dignity therapy, no effects were observed in the meta-analysis. Moreover, important methodological and clinical concerns precluded us to make sound clinical recommendations with the available evidence. OPEN SCIENCE FRAMEWORK DOI REGISTRATION: https://doi.org/10.17605/OSF.IO/4YMTK .

Model-informed precision dosing of antimicrobial drugs in pediatrics: experiences from a pilot scale program.

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16 years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all.  Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research may improve dosing practices altogether.

Standardization and validation of a novel UPLC-MS/MS method to quantify first line anti-tuberculosis drugs in plasma and dried blood spots.

Tuberculosis (TB) is a high-burden infectious disease with high prevalence and mortality rates. The first-line anti-TB drugs include isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB). At present, the standard method of blood sampling for therapeutic drug monitoring (TDM) analysis is venipuncture. Dried blood spots (DBS) are a minimally invasive method for collecting small quantities of whole blood from fingertips. The aim of the current study was to develop an ultrahigh-performance liquid chromatography technique coupled to tandem mass spectrometry (UPLC-MS/MS) for simultaneous quantification of the first-line anti-TB drugs in human plasma and DBS as a sampling alternative. The separation and detection conditions were optimized to quantify INH, RMP, PZA, and EMB in both matrices in an ACQUITY UPLC H Class system coupled to a XEVO TQD detector. Chromatographic separation was performed through an Acquity HSS T3 column (2.1 × 100 mm, 1.8 µm) with 0.1% formic acid in water and acetonitrile as the mobile phase. The total run time was 7 min for both methods, with retention time in plasma of 0.85, 1.22, 3.16, and 4.04 min and 0.74, 0.87, 0.97, and 4.16 min for EMB, INH, PZA, and RMP in DBS, respectively. The bioanalytical methods developed were proved selective, linear, precise, and accurate (inter- and intra-assay); the matrix effect was demonstrated to be within the established limits. Short- and long-term stability, freeze-thaw cycles for plasma, and short-term stability for DBS were established. A total of 15 patients with 46 ± 17 (mean ± SD) years old were included, and anti-TB drug concentrations were quantified on plasma and DBS as proof of concept. Based on RMP and INH plasma concentrations (Cp), and Bayesian estimation of individual pharmacokinetic parameters, a dose adjustment was necessary for 93% of patients. The slopes of the correlation lines between plasma and DBS concentrations of RMP, EMB, INH, and PZA were 0.5321, 0.8125, 0.5680, and 0.6791, respectively. Finally, significant correlations (p < 0.05) were observed between DBS and plasma concentrations for RMP (r2 = 0.6961), EMB (r2 = 0.4369), INH (r2 = 0.8675) and PZA (r2 = 0.7363). A simple, fast, and reliable UPLC-MS/MS method was developed to quantify first-line anti-TB drugs in plasma and DBS, which provides an easy sampling and storage to be applied as a new strategy for TDM in patients with TB.

Integrative model for self-perception of well-being in cancer.

PURPOSE: Continual illness uncertainty can affect how people perceive and interpret their well-being. Some cognitive and spiritual factors may be involved in the management of disruptive thoughts and emotions that can emerge during the experience of cancer. MATERIAL AND METHODS: An evidence-based integrative model was developed to evaluate and show the role that mindfulness, acceptance, self-efficacy, uncertainty, meaning, and purpose in life play in the self-perception of well-being in individuals with cancer. This evidence-based integrative model was conducted using relevant and selected studies. RESULTS: An integrative model for self-perception of well-being has been proposed. This model integrates evidence-based findings and provides clear principles for clinicians and researchers. This integrative model proposes that mindfulness, acceptance, self-efficacy perception, and uncertainty can predict how people with cancer perceive their well-being. The model also posits that meaning and purpose in life can act as mediators or moderators of this prediction. CONCLUSIONS: This integrative model involves the multidimensionality of human beings and facilitates the understanding of some key factors for the design of therapeutic approaches such as Acceptance & Commitment Therapy or Meaning-Centered Psychotherapy.IMPLICATIONS FOR REHABILITATIONMindfulness, acceptance, self-efficacy, uncertainty, meaning, and purpose in life can be highly relevant for clinical oncology.An integrative model is proposed to understand the combined influence of these factors on patients with cancer.This model may favor a better integration of well-known interventions, such as Mindfulness-based approaches, Acceptance and Commitment Therapy (ACT), and Meaning-Centered Psychotherapy (MCP).

Abscopal Effect, Extracellular Vesicles and Their Immunotherapeutic Potential in Cancer Treatment.

The communication between tumor cells and the microenvironment plays a fundamental role in the development, growth and further immune escape of the tumor. This communication is partially regulated by extracellular vesicles which can direct the behavior of surrounding cells. In recent years, it has been proposed that this feature could be applied as a potential treatment against cancer, since several studies have shown that tumors treated with radiotherapy can elicit a strong enough immune response to eliminate distant metastasis; this phenomenon is called the abscopal effect. The mechanism behind this effect may include the release of extracellular vesicles loaded with damage-associated molecular patterns and tumor-derived antigens which activates an antigen-specific immune response. This review will focus on the recent discoveries in cancer cell communications via extracellular vesicles and their implication in tumor development, as well as their potential use as an immunotherapeutic treatment against cancer.

Meaning and purpose in life, happiness, and life satisfaction in cancer: Systematic review with meta-analysis.

OBJECTIVE: To summarize current evidence on the potential cross-sectional and longitudinal association between meaning or purpose in life and subjective happiness or life satisfaction among cancer patients. METHODS: A systematic review with meta-analysis and meta-regression was conducted. CINAHL (via EBSCOhost), Embase, PubMed, and PsycINFO (via ProQuest) were searched from inception to 31 December 2022. In addition, manual searches were performed. The risk of bias in cross-sectional and longitudinal studies was assessed using the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool, respectively. Certainty in the evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Meta-regressions and sensitivity analyses were performed to explore potential sources of heterogeneity. RESULTS: We included 13 cross-sectional studies, comprising 12 different samples, and a longitudinal study. A total of 4968 individuals with cancer were interviewed across included studies. Certainty in the evidence was judged as very low for all outcomes, which was associated to serious concerns on risk of bias and imprecision of the results, and very serious concerns on indirectness of evidence. The assessed studies showed a marked heterogeneity in terms of participants' clinical (i.e., disease stage) and sociodemographic factors. A lack of reporting of these clinical and sociodemographic aspects were also evident among included studies. CONCLUSIONS: The wide number of methodological flaws detected in this systematic review preclude to make any clinical recommendation. More rigorous high-quality observational studies should guide future research on this topic.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death.

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.