Developing a Transdiagnostic Measure of the Subtypes of Repetitive Thought

Rumination, worry, post-event processing and similar constructs have been recently grouped under the broader transdiagnostic concept of repetitive thought. Repetitive thought has been implicated as a maintaining factor across a broad range of disorders (such as depression, generalised anxiety disorder, and social anxiety disorder), but has also been proposed to be part of helpful processes (such as problem solving and post-traumatic growth). To account for these contradictory outcomes, it has been proposed that repetitive thought can be broken down into maladaptive abstract thought and relatively adaptive concrete thought (Watkins, 2008). However, there are currently no measures in the existing literature that assess these subtypes of repetitive thought. This thesis describes the development and validation of a transdiagnostic measure of abstract and concrete repetitive thought: the Repetitive Thought Scale (RTS). Studies 1a-4 describe the psychometric properties of a trait version of the RTS in three online samples and one university sample, whereas Studies 1b-4 describe the psychometric properties of a state version of the scale. Both versions of the scale demonstrated good factor structure, excellent reliability, and good predictive validity with symptoms of psychopathology. Interestingly, and contrary to hypothesis, concrete repetitive thought was found to be more strongly related to symptoms of psychopathology than abstract thought in these non-clinical samples. Study 5 demonstrated that the abstract subscale of the state version could be used as a manipulation check for experiments that involve repetitive thought inductions. Study 6 explored a longitudinal mediation model predicting psychopathology symptoms at the six-month follow-up using baseline symptoms as predictors. Only metacognitive beliefs about repetitive thought emerged as mediating variables in this model. Study 7 revealed that only abstract thought distinguished between never, previously and currently depressed individuals in a community clinical sample. Studies 8 and 9 compared the efficacy of rumination cues action and concrete thinking as strategies for reducing the frequency of repetitive thought. However, neither strategy emerged as efficacious in these experimental studies. Overall, these studies highlight the development of the repetitive thought scale, which is a reliable and valid transdiagnostic measure of abstract and concrete repetitive thought

Beyond memory: exploring the value of social cognition for older adults with neurocognitive disorders

Neurocognitive disorders involves progressive decline in cognition, function, behavior and needs. Recent developments have identified the need to characterize social cognition in individuals with neurocognitive impairments to support uncertainty in clinical decision making, treatment plans and monitoring individual change. Routine social cognition assessments have thus been more recently used and adopted in persons with dementia or mild cognitive impairment. This work serves to summarize current assessments and provide a discourse on the practicality of available social cognition tools, its implication in clinical practice and key future directions. We highlight advantages in establishing validated, multicomponent measures of social cognition for people with neurocognitive disorders

Is Cytoreductive Nephrectomy Still a Standard of Care in Metastatic Renal Cell Carcinoma?

Cytoreductive nephrectomy has been an integral part of management in metastatic renal cell carcinoma for patients with good performance status, based on the benefit shown by prospective trials in the interferon era and retrospective trials in the targeted therapies era. Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), the first prospective phase III trial comparing a targeted agent alone (sunitinib) versus nephrectomy plus sunitinib, has been recently published, showing non-inferiority for the nephrectomy-sparing arm. In this article, we discuss the impact of nephrectomy including its immune-mediated effects, surgical morbidity and mortality, and the clinical data supporting the indications of nephrectomy in order to analyze the CARMENA trial in context, with the aim to identify optimal strategies for different patient populations in the metastatic setting

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies

INTRODUCTION: In this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (≥6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any interventions

Social health and subsequent cognitive functioning in people aged 50 years and older:examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. Methods: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). Findings: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001–0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000–0·002]) and in delayed recall (PIE 0·001 [0·000–0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000–0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. Interpretation: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. Funding: EU Joint Programme—Neurodegenerative Disease Research (JPND) and Alzheimer's Society. Translation: For the Swedish translation of the abstract see Supplementary Materials section.</p

Social health and subsequent cognitive functioning in people aged 50 years and older:examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. Methods: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). Findings: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001–0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000–0·002]) and in delayed recall (PIE 0·001 [0·000–0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000–0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. Interpretation: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. Funding: EU Joint Programme—Neurodegenerative Disease Research (JPND) and Alzheimer's Society. Translation: For the Swedish translation of the abstract see Supplementary Materials section.</p

Recognition of social health: A conceptual framework in the context of dementia research

Objective: The recognition of dementia as a multifactorial disorder encourages the exploration of new pathways to understand its origins. Social health might play a role in cognitive decline and dementia, but conceptual clarity is lacking and this hinders investigation of associations and mechanisms. The objective is to develop a conceptual framework for social health to advance conceptual clarity in future studies. Process: We use the following steps: underpinning for concept advancement, concept advancement by the development of a conceptual model, and exploration of its potential feasibility. An iterative consensus-based process was used within the international multidisciplinary SHARED project. Conceptual framework: Underpinning of the concept drew from a synthesis of theoretical, conceptual and epidemiological work, and resulted in a definition of social health as wellbeing that relies on capacities both of the individual and the social environment. Consequently, domains in the conceptual framework are on both the individual (e.g., social participation) and the social environmental levels (e.g., social network). We hypothesize that social health acts as a driver for use of cognitive reserve which can then slow cognitive impairment or maintain cognitive functioning. The feasibility of the conceptual framework is demonstrated in its practical use in identifying and structuring of social health markers within the SHARED project. Discussion: The conceptual framework provides guidance for future research and facilitates identification of modifiable risk and protective factors, which may in turn shape new avenues for preventive interventions. We highlight the paradigm of social health in dementia as a priority for dementia research

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality

Inhibidores del punto de control inmune en cáncer pulmonar de células no pequeñas en etapa temprana: ¿Nuevo estándar de tratamiento?

Resumen: El cáncer de pulmón es el primer cáncer en incidencia y en mortalidad a nivel mundial. El tipo histológico más frecuente es el cáncer pulmonar de células no pequeñas (CPCNP). En etapa temprana, la resección es el tratamiento curativo estándar, pero la recaída es alta, lo que se podría explicar por enfermedad micrometastásica. La quimioterapia adyuvante y neoadyuvante tienen un escaso beneficio en sobrevida libre de enfermedad y sobrevida global, por lo que se han estudiado nuevas estrategias. Los inhibidores de puntos de control inmunitario (ICI) actúan aumentando la vigilancia del sistema inmune. Se utilizan hace años en CPCNP etapa avanzada, sin embargo, nuevos esquemas en etapa temprana, ya sea en adyuvancia, neoadyuvancia o ambas, han demostrado un importante beneficio en los desenlaces estudiados. Esta revisión tiene por objetivo describir la racionalidad biológica de los ICI en CPCNP en etapa temprana y discutir sobre los ensayos y desenlaces. Abstract: Worldwide, lung cancer is the first cancer in incidence and mortality. The most common histological type is non-small cell lung cancer (NSCLC). At an early stage, resection is the standard curative treatment, but relapse is high, which could be explained by micrometastatic disease. Adjuvant and neoadjuvant chemotherapy have little benefit in disease-free survival and overall survival, which is why new strategies have been studied. Immune checkpoint inhibitors (ICI) act by increasing the surveillance of the immune system. They have been used for years in advanced stage NSCLC, however, new schemes in earlier stages, be it as adjuvant therapy, neoadjuvant therapy or both, have demonstrated an important benefit in the endpoints studied. This review aims to describe the biologic rationale of ICIs in early-stage NSCLC and discuss the selected trials and endpoints