Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset. Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05. Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05). Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors

The PERMA well-being model and music facilitation practice: Preliminary documentation for well-being through music provision in Australian schools

The aim of this study was to consider how we can invest in music-making to promote well-being in school contexts. Web-based data collection was conducted where researchers identified 17 case studies that describe successful music programs in schools in Australia. The researchers aligned content from these case studies into the five categories of the PERMA well-being model: Positive emotions, Engagement, Relationships, Meaning, and Accomplishment, in order to understand how each well-being element was realised through the music programs. The results indicate that the element of the PERMA well-being model that relates to relationships was described most often. Collaboration and partnership between students, teachers, and staff in schools, and local people in the community such as parents, local entrepreneurs, and musicians were repeatedly identified as a highly significant contributing factor in the success of the music program. The school leaders? roles in providing opportunities for students to experience musical participation and related activities (engagement) and valuing these experiences (meaning) were also crucial in the facilitation of the music programs. The findings of this study indicate that tailored music and relationship-centred music programs in schools not only increase skills and abilities of the students, but also improve the psychosocial well-being of the students and the community

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian longitudinal study on aging

Introduction: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence. Methods: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status. Results: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70, P = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67, P = .024). Discussion: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis

Spontaneous singing and musical agency in the everyday home lives of three- and four-year-old children

Spontaneous singing permeates the lives of young children and can provide insights into the social and personal worlds of young children at home. Research into young children’s singing has traditionally been dominated by studies framed by developmental perspectives. However, developmental approaches run the risk of overlooking the ways in which spontaneous singing is useful and meaningful to young children. Despite increased interest in the musical lives of young children, there exists very little research into young children’s musical lives at home, largely because the home can be a difficult space to access for research purposes. This chapter is based on research undertaken from audio recordings of 15 3- and 4-year-old children who were recorded for continuous periods at home using all-day recording technology. I draw on ideas from music sociology and childhood studies to illustrate how children use singing as a tool of agency in their interactions with others and to manage their own experience

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1–2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1–2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1–2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND

The German Music@Home: Validation of a questionnaire measuring at home musical exposure and interaction of young children.

The present study introduces the German version of the original version of the Music@Home questionnaire developed in the UK, which systematically evaluates musical engagement in the home environment of young children. Two versions are available, an Infant version for children aged three to 23 months and a Preschool version for children aged two to five and a half years. For the present study, the original Music@Home questionnaire was translated from English into German and 656 caregivers completed the questionnaire online. A confirmatory factor analysis showed moderate to high fit indices for both versions, confirming the factor structure of the original questionnaire. Also, the reliability coefficients for the subscales (Parental beliefs, Child engagement with music, Parent initiation of singing, Parent initiation of music-making for the Infant version and Parental beliefs, Child engagement with music, Parent initiation of music behavior and Breadth of musical exposure for the Preschool version) ranged from moderate to high fits. Furthermore, the test-retest analysis (N = 392) revealed high correlations for the general factor and all subscales confirming their internal reliability. Additionally, we included language questionnaires for children of two and three years of age. Results showed that higher scores on the Music@Home questionnaire were moderately associated with better language skills in two-year-olds (N = 118). In sum, the study presents the validated German Music@Home questionnaire, which shows good psychometric properties. The two versions of the questionnaire are available for use in order to assess home musical engagement of young children, which could be of interest in many areas of developmental research

Pain and Frailty in Hospitalized Older Adults

Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: Analysis of the REPOSI registry

Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease