Comparative Meta-Analysis of Minimally Invasive and Conventional Approaches for Caries Removal in Permanent Dentition.

Background and Objectives: Addressing deep carious lesions poses significant challenges in daily dental practice due to the inherent complexity of their treatment. Traditionally, complete removal of carious tissues has been the norm, potentially leading to pulp tissue exposure and subsequent pulpitis. In contemporary dentistry, there is a growing preference for minimally invasive techniques, such as selective removal, offering a more conservative approach with enhanced predictability and success rates. Materials and Methods: Our study commenced with a comprehensive systematic review. After that, we performed a meta-analysis focused exclusively on randomized controlled trials involving permanent dentition. Our investigation incorporated seven selected articles, which scrutinized success rates and the incidence of pulp exposure in minimally invasive techniques (MIT) versus conventional techniques (CT). Statistical analysis employed U Mann-Whitney and Wilcoxon tests to interpret the results. Results: Although the difference did not reach statistical significance, MIT demonstrated marginally superior success rates compared to CT. Furthermore, MIT exhibited a lower percentage of pulp exposure when contrasted with CT. However, due to the limited sample size, statistical significance for this difference could not be established. Conclusions: Minimally invasive techniques for caries removal emerge as a conservative and promising approach to safeguard pulp tissues in comparison to conventional techniques. The need for additional randomized controlled trials is emphasized to unequivocally establish the superior success rates of these procedures over their conventional counterparts.

Associated factors for fear of COVID-19 scale in long-term care settings in Spain.

OBJECTIVE: To examine the relationship between the Fear of COVID-19 Scale (FCV-19S) score and sociodemographic, health, emotional and behavioural factors, in a cross-sectional observational study in 447 older adults living in long-term care (LTC) settings in Madrid (Spain). METHODS: The sample was stratified by nursing home ownership, geographical location, and size. Multiple linear regression analysis was used using backward elimination to identify factors that explained associations with fear, and logistic regression models were used to examine its role as a predictor of adherence to preventive measures. RESULTS: The mean age of the participants was 83.8 years, most were female, had had COVID-19, and were worried about the pandemic. The average score of the FCV-19S was 18.36 (SD: 8.28; range: 7-35), and the variables associated in the multiple linear regression model (explained variance: 34.00%) were being female, lower level of education, satisfaction with life and the residential home, and higher worry about the pandemic. The logistic regression models showed that fear of COVID-19 was a predictor of adherence to preventive measures like wearing facemasks, washing hands, and avoiding physical contact. CONCLUSIONS: fear of COVID-19 was significantly related with sex and subjective factors as life satisfaction and worry; and it influences older people's preventive behaviour. Interventions aimed at reducing fear and promoting adherence to preventive measures would improve their mental health and well-being.

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.

Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

Sulfur nanocomposites with insecticidal effect for the control of Bactericera cockerelli.

The purpose of this research was to synthesize nanocomposites consisting of sulfur nanoparticles coated with eucalyptus and rosemary essential oils to determine the insecticidal effect in the control of nymphs of paratrioza (Bactericera cockerelli (Sulc) (Hemiptera: Triozidae)) in potato crops. A solution of thiosulfate was reduced to elemental sulfur, and the sulfur nanoparticles were coated with eucalyptus and rosemary essential oils with the three concentrations of 0.25%, 0.5%, and 0.75%. The samples were characterized by UV-visible spectroscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. The insecticidal efficacy of the nanocomposites was evaluated in the entomology laboratory 24, 48, and 72 h after application. Furthermore, efficacy was compared to the commercial insecticide thiamethoxam (0.25%) and a control. The results show that eucalyptus nanocomposites with oil concentrations of 0.25%, 0.5%, and 0.75% and rosemary nanocomposites with an oil concentration of 0.5% have an insecticidal efficacy of 100% for the control of insect nymphs 24 h after application. The insecticidal efficacy of rosemary nanocomposites with oil concentrations of 0.25% and 0.75% increases over time and reaches 100% at 24 and 72 h, respectively. The synthesized nanocomposites are more effective in controlling nymphs of paratrioza than the commercial insecticide thiamethoxam; thus, they could be used for the development of new insecticides.

The Five "Ws" of Frailty Assessment and Chronic Lymphocytic Leukemia: Who, What, Where, Why, and When.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person's overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws.

A systematic review of ageing in place among Indigenous People in Canada, USA, México, Chile and New Zealand.

The ageing in place (AIP) model enjoys widespread recognition in gerontology and has been strongly encouraged through social policy. However, progress remains to be made in terms of analysing AIP for minority groups and groups with diverse life pathways in old age. This systematic review aims to identify studies that address the AIP model in indigenous communities, answering the following questions: In which geographical contexts and for which Indigenous Peoples have AIP been researched? Which physical dimensions are considered in the assessment of AIP? Which social dimensions are considered in the assessment of AIP? This systematic review applied the SALSA (Search, Appraisal, Synthesis and Analysis) method to AIP among Indigenous older adults on the Web of Science, PsycINFO, MEDLINE and Scopus digital platforms for publications from 2011 to 2021. We identified 12 studies conducted in five countries in North and South America and Oceania. The results show that the following elements of the physical environment are assessed: household, neighbourhood, local surroundings or reserve and native territories. Meanwhile, assessed elements of the social environment are as follows: personal characteristics, attachment to place, social networks, social participation and social policies. There is discussion of the need to develop AIP in order to promote successful ageing among Indigenous older adults.

[Studying loneliness and social support networks among older people: a systematic review in Europe.] / La investigación sobre soledad y redes de apoyo social en las personas mayores: una revisión sistemática en Europa.

OBJECTIVE: During the ageing process the loss of family and social relationships is frequent which conditions loneliness, similarly the current COVID-19 pandemic has generated more social limitations in this age group and has increased the risk factors to trigger feelings of loneliness. This paper aimed to examine how loneliness among older people had been studied in Europe over the last ten years. Specific objectives were: i) to describe the methodological aspects; ii) to identify the scales or questions for the assessment of loneliness; iii) what were the main variables or dimensions that were related to loneliness in old age. METHODS: A total of 1,591 articles were found in WoS and Scopus digital platforms. After initial assessment of titles and abstracts, full text reading and review of the established criteria, 42 scientific articles were finally included in the systematic review. RESULTS: The countries that had carried out the most studies were the Netherlands and Spain. Most of the research was quantitative and uses the De Jong Gierveld Loneliness Scale (DJGLS) and the University of California at Los Angeles (UCLA) Loneliness Scale. The most analysed variables were: marital status, household structure, social support networks, social participation, depression, health problems, co-morbidity and physical functioning. CONCLUSIONS: The scientific interest in studying loneliness, with a focus on social support networks, in older people in Europe and strategically addressing loneliness as a public health problem is confirmed.

OBJETIVO: Durante el proceso de envejecimiento es frecuente la pérdida de relaciones familiares y sociales, lo cual condiciona la soledad. Además, la actual pandemia de la COVID-19 ha generado más limitaciones en las relaciones sociales de este grupo de edad y ha aumentado los factores de riesgo para desencadenar sentimientos de soledad. Este trabajo tuvo el objetivo de examinar cómo se había estudiado la soledad en las personas mayores en Europa en los últimos diez años. Se propusieron como objetivos específicos: i) describir los aspectos metodológicos; ii) identificar las escalas o preguntas para la valoración de la soledad; iii) cuáles eran las principales variables o dimensiones que se relacionaban con la soledad en la vejez, priorizando el rol de las redes de apoyo social. METODOS: Se encontraron 1.591 artículos en total en las plataformas digitales WoS y Scopus. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los criterios establecidos, al final se incluyeron en la revisión sistemática 42 artículos científicos. RESULTADOS: Los países que más estudios habían realizado eran Países Bajos y España, en su mayoría las investigaciones eran cuantitativas y utilizaban las escalas De Jong Gierveld Loneliness Scale (DJGLS) y University of California at Los Angeles (UCLA) Loneliness Scale. Las variables más analizadas fueron: estado civil, estructura del hogar, redes de apoyo social, participación social, depresión, problemas de salud, comorbilidad y funcionalidad física. CONCLUSIONES: Se confirma el interés científico por estudiar la soledad, con un énfasis central en las redes de apoyo social, en las personas mayores en Europa y abordar estratégicamente la soledad como un problema de Salud Pública.

Veno-venous ECLS rescue for a heart transplant recipient with COVID-19, a case report.

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).

La investigación sobre soledad y redes de apoyo social en las personas mayores: una revisión sistemática en Europa / Studying loneliness and social support networks among older people: a systematic review in Europe

FUNDAMENTOS: Durante el proceso de envejecimiento es frecuente la pérdida de relaciones familiares y sociales, lo cual condiciona la soledad. Además, la actual pandemia de la COVID-19 ha generado más limitaciones en las relaciones sociales de este grupo de edad y ha aumentado los factores de riesgo para desencadenar sentimientos de soledad. Este trabajo tuvo el objetivo de examinar cómo se había estudiado la soledad en las personas mayores en Europa en los últimos diez años. Se propusieron como objetivos específicos: i) describir los aspectos metodológicos; ii) identificar las escalas o preguntas para la valoración de la soledad; iii) cuáles eran las principales variables o dimensiones que se relacionaban con la soledad en la vejez, priorizando el rol de las redes de apoyo social. MÉTODOS: Se encontraron 1.591 artículos en total en las plataformas digitales WoS y Scopus. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los criterios establecidos, al final se incluyeron en la revisión sistemática 42 artículos científicos. RESULTADOS: Los países que más estudios habían realizado eran Países Bajos y España, en su mayoría las investigaciones eran cuantitativas y utilizaban las escalas De Jong Gierveld Loneliness Scale (DJGLS) y University of California at Los Angeles (UCLA) Loneliness Scale. Las variables más analizadas fueron: estado civil, estructura del hogar, redes de apoyo social, participación social, depresión, problemas de salud, comorbilidad y funcionalidad física. CONCLUSIONES: Se confirma el interés científico por estudiar la soledad, con un énfasis central en las redes de apoyo social, en las personas mayores en Europa y abordar estratégicamente la soledad como un problema de Salud Pública.(AU)

BACKGROUND: During the ageing process the loss of family and social relationships is frequent which conditions loneliness, similarly the current COVID-19 pandemic has generated more social limitations in this age group and has increased the risk factors to trigger feelings of loneliness. This paper aimed to examine how loneliness among older people had been studied in Europe over the last ten years. Specific objectives were: i) to describe the methodological aspects; ii) to identify the scales or questions for the assessment of loneliness; iii) what were the main variables or dimensions that were related to loneliness in old age. METHODS: A total of 1,591 articles were found in WoS and Scopus digital platforms. After initial assessment of titles and abstracts, full text reading and review of the established criteria, 42 scientific articles were finally included in the systematic review. RESULTS: The countries that had carried out the most studies were the Netherlands and Spain. Most of the research was quantitative and uses the De Jong Gierveld Loneliness Scale (DJGLS) and the University of California at Los Angeles (UCLA) Loneliness Scale. The most analysed variables were: marital status, household structure, social support networks, social participation, depression, health problems, co-morbidity and physical functioning. CONCLUSIONS: The scientific interest in studying loneliness, with a focus on social support networks, in older people in Europe and strategically addressing loneliness as a public health problem is confirmed.(AU)

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY.

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.

La desconocida mortalidad de la población en las residencias de personas mayores de España / Unknown mortality of the population in long-term care homes in Spain

Es necesario conocer la mortalidad de las personas mayores que viven en residencias para evaluar sus determinantes, incluyendo las características estructurales y organizativas de estos centros y su relación con la utilización de servicios sanitarios y sociales. Al querer investigar la mortalidad de la población mayor de 65 años que vive en residencias durante la COVID-19 nos encontramos con la imposibilidad de identificar a las personas fallecidas con domicilio habitual en residencias y, en consecuencia, de conocer el número de defunciones y sus causas. En esta nota de campo describimos esta situación anómala y proponemos una solución: el cumplimiento de la ley que obliga a todos los ciudadanos al empadronamiento en el domicilio habitual, lo que debería ser exigido en el proceso de admisión a una residencia. Se aseguraría así la disponibilidad de los datos necesarios para conocer la mortalidad de la población que reside en una residencia. (AU)

It seems necessary to assess the mortality of older people living in long-term care homes to examine its determinants, including the structural and organizational characteristics of these centers and their relationship with the use of health and social services. Attempting to investigate the mortality of the population over 65 years of age living in long-term care homes during COVID-19, we were not able to identify those who died at their long-term care home and, consequently, to know their number of deaths and their causes. In this field note, we describe this anomalous situation and propose a solution: compliance with the law that obliges all citizens to register at their usual address, which should be required in the process of admission to a residence. This would ensure the availability of the necessary data to know the mortality of the population residing in a residence. (AU)

The Impact of COVID-19 on Nursing Homes: Study Design and Population Description.

Nursing homes for the elderly in Spain have experienced high rates of infection and mortality from COVID-19, although rates have varied from one region to another. Madrid is the region where most institutionalized older adults have died from the coronavirus. However, there is little known about the psychosocial and environmental factors involved in the high incidence of COVID-19 among the institutionalised population in this region. This article describes the protocol of a study on nursing homes during the SARS-CoV-2 pandemic in the Autonomous Community of Madrid (hereafter: Region of Madrid or Madrid Region) and provides information on the study design, measures used, and characteristics of the population studied. A questionnaire about life in nursing homes during the COVID-19 pandemic was designed and a total of 447 persons over 60 years of age without cognitive impairment-220 in private nursing homes and 227 in public nursing homes-participated by answering questions about different topics: personal situations during the pandemic, feelings and methods of coping, residential environment, health, quality of life, ageism, and self-perception of ageing. The institutionalised person profile discussed in this study was an old woman, widowed, without children, with a low level of education, with multimorbidity, and who perceived her health and quality of life positively. Most of the participants were very concerned about COVID-19 and its effects. In fact, 38% had been diagnosed with COVID-19, of whom 20% were admitted to hospital and 20% had suffered negative impacts, such as pain and neurological problems. In addition, 70% of the residents remained confined to their rooms, which increased their perceptions of loneliness and social isolation. The worst-rated aspects of the nursing home resulted from the restrictive measures imposed on nursing homes during the pandemic. This research offers useful material for understanding the pandemic and its consequences from the perspective of the older institutionalised population, which could provide insights for designing public policies.

Social Image of Old Age, Gendered Ageism and Inclusive Places: Older People in the Media.

Ageism promotes the exclusion of older people from society by generating a negative image that they also internalize. The aim of this article is to investigate older people's social self-image, through statements broadcast on a national Spanish radio program aimed at this group. A qualitative analysis was conducted for a random sample from the sound archive for the Radio Nacional de España program Juntos Paso a Paso (Together, Step by Step) (2008-2021), using codes based on the pillars and determinants of active ageing and the three dimensions of ageism. Intercoder agreement was calculated. There were significant findings regarding ageism, gendered ageism and ageing in place, with differences according to size of municipal area. The program in question can be considered a viable secondary source for the research aim. Ageism is most commonly manifested through implicit opinions and invisibilization in family and social contexts. Care activities play a notably central role in responses related to gendered ageism. In relation to ageing in place, older people prefer their habitual environment when they have moderate care needs and accept moves to nursing homes when their needs increase.

Validation of the Spanish Version of the Fear of COVID-19 Scale (FCV-19S) in Long-Term Care Settings.

Fear of coronavirus disease 2019 (COVID-19) is one of the main psychological impacts of the actual pandemic, especially among the population groups with higher mortality rates. The Fear of COVID-19 Scale (FCV-19S) has been used in different scenarios to assess fear associated with COVID-19, but this has not been done frequently in people living in long-term care (LTC) settings. The present study is aimed at measuring the psychometric properties of the Spanish version of the FCV-19S in residents in LTC settings, following both the classical test theory (CTT) and Rasch model frameworks. The participants (n = 447), aged 60 years or older, were asked to complete the FCV-19S and to report, among other issues, their levels of depression, resilience, emotional wellbeing and health-related quality of life with validated scales. The mean FCV-19S score was 18.36 (SD 8.28, range 7−35), with higher scores for women, participants with lower education (primary or less) and higher adherence to preventive measures (all, p < 0.05). The Cronbach's alpha for the FCV-19S was 0.94. After eliminating two items due to a lack of fit, the FCV-19S showed a good fit to the Rasch model (χ2 (20) = 30.24, p = 0.019, PSI = 0.87), with unidimensionality (binomial 95% CI 0.001 to 0.045) and item local independency. Question 5 showed differential item functioning by sex. The present study shows that the FCV-19S has satisfactory reliability and validity, which supports its use to effectively measure fear in older people living in LTC settings. This tool could help identify risk groups that may need specific health education and effective communication strategies to lower fear levels. This might have a beneficial impact on adherence to preventive measures.

Residential Environment Assessment by Older Adults in Nursing Homes during COVID-19 Outbreak.

The most vulnerable residential settings during the COVID-19 pandemic were older adult's nursing homes, which experienced high rates of incidence and death from this cause. This paper aims to ascertain how institutionalized older people assessed their residential environment during the pandemic and to examine the differences according to personal and contextual characteristics. The COVID-19 Nursing Homes Survey (Madrid region, Spain) was used. The residential environment assessment scale (EVAER) and personal and contextual characteristics were selected. Descriptive and multivariate statistical analysis were applied. The sample consisted of 447 people (mean age = 83.8, 63.1% = women, 50.8% = widowed, 40% = less than primary studies). Four residential assessment subscales (relationships, mobility, residential aspects, privacy space) and three clusters according to residential rating (medium-high with everything = 71.5% of cases, low with mobility = 15.4%, low with everything = 13.1%) were obtained. The logistic regression models for each cluster category showed to be statistically significant. Showing a positive affect (OR = 1.08), fear of COVID-19 (OR = 1.06), high quality of life (OR = 1.05), not having suspicion of depression (OR = 0.75) and performing volunteer activities (OR = 3.67) were associated with the largest cluster. It is concluded that a better residential evaluation was related to more favourable personal and contextual conditions. These results can help in the design of nursing homes for older adults in need of accommodation and care to facilitate an age-friendly environment.

[Unknown mortality of the population in long-term care homes in Spain]. / La desconocida mortalidad de la población en las residencias de personas mayores de España.

It seems necessary to assess the mortality of older people living in long-term care homes to examine its determinants, including the structural and organizational characteristics of these centers and their relationship with the use of health and social services. Attempting to investigate the mortality of the population over 65 years of age living in long-term care homes during COVID-19, we were not able to identify those who died at their long-term care home and, consequently, to know their number of deaths and their causes. In this field note, we describe this anomalous situation and propose a solution: compliance with the law that obliges all citizens to register at their usual address, which should be required in the process of admission to a residence. This would ensure the availability of the necessary data to know the mortality of the population residing in a residence.

Active ageing profiles among older adults in Spain: A Multivariate analysis based on SHARE study.

BACKGROUND: Following the active ageing model based on the Health, Lifelong Learning, Participation and Security pillars, this research has a twofold objective: i) to classify older adults according to active ageing profiles, taking into account the four pillars, and ii) to ascertain the relationship between the profiles and personal and contextual factors, as well as well-being and quality of life in old age. METHODS: A study sample of 5,566 Spanish older adults who participated in wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was included. Data were analysed in different steps applying several statistical analyses (Principal Component, Cluster, Discriminant, Multiple Correspondence and bivariate analysis with Pearson chi-square and ANOVA). RESULTS: Five older adult profiles were obtained (I: with moderate activity; II: quasi-dependents; III: with active ageing-limiting conditions; IV: with diverse and balanced activity; V: with excellent active ageing conditions). The first three profiles were characterised by subjects with a high average age, low educational level, who were retired or housewives, and who perceived a moderate level of loneliness, satisfaction with the social network and quality of life, as well as having a larger family network, but living in small households or alone. In contrast, the latter two profiles showed better personal and contextual conditions, well-being and quality of life. DISCUSSION AND CONCLUSIONS: The multidimensional approach to active ageing followed in this article has revealed the presence of several older adult profiles, which are confined to groups with better or worse active ageing conditions. In this context, if ageing is a process that reflects the previous way of life, intervention priorities will have to consider actions that promote better conditions during the life cycle.

Building a Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology Added Value Framework for Hematologic Malignancies: A Comparative Analysis of Existing Tools.

OBJECTIVES: The Innovative Medicines Initiative-funded, multistakeholders project Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology (HARMONY) created a task force involving patient organizations, medical associations, pharmaceutical companies, and health technology assessment/regulator agencies' representatives to evaluate the suitability of previously established value frameworks (VFs) for assessing the clinical and societal impact of new interventions for hematologic malignancies (HMs). METHODS: Since the HARMONY stakeholders identified the inclusion of patients' points of view on evaluating VFs as a priority, surveys were conducted with the patient organizations active in HMs and part of the HARMONY network, together with key opinion leaders, pharmaceutical companies, and regulators, to establish which outcomes were important for each HM. Next, to evaluate VFs against the sources of information taken into account (randomized clinical trials, registries, real-world data), structured questionnaires were created and filled by HARMONY health professionals to specify preferred data sources per malignancy. Finally, a framework evaluation module was built to analyze existing clinical VFs (American Society of Clinical Oncology, European Society of Medical Oncology, Magnitude of Clinical Benefit Scale, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, Institute for Clinical and Economic Review, National Comprehensive Cancer Network Evidence Blocks, and patient-perspective VF). RESULTS: The comparative analysis describes challenges and opportunities for the use of each framework in the context of HMs and drafts possible lines of action for creating or integrating a more specific, patient-focused clinical VF for HMs. CONCLUSIONS: None of the frameworks meets the HARMONY goals for a tool that applies to HMs and assesses in a transparent, reproducible, and systematic way the therapeutic value of innovative health technologies versus available alternatives, taking a patient-centered approach and using real-world evidence.

TRAF3 alterations are frequent in del-3'IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features.

Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3'IGH (del-3'IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3'IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3'IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3'IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3'IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3'IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.