Spina bifida and cardiorespiratory profile: the impact of leisure sport activities on physical fitness.

PURPOSE: The aim of the present study is to evaluate a population of young patients affected by Spina Bifida (SB) to describe their cardiorespiratory function and bone mineral density profile, analyzing any differences between people performing and those who do not perform sports activity. The study also aimed to rule out possible congenital heart disease associated with spina bifida, considering the common origin of certain cardiac structures with those found to be altered in SB patients. METHODS: Thirty-four young patients, aged between 12 and 22 years, diagnosed with spinal dysraphism (SD), have been clinically described and, in order to evaluate their physical fitness, functional capacity and bone mass, almost all of them underwent a complete cardiorespiratory assessment, including electrocardiogram (ECG), echocardiogram, Cardiopulmonary Exercise Test (CPET), body composition analysis using bioimpedance analysis (BIA) and Dual Energy X-ray Absorptiometry (DEXA), as well as the estimation of bone mineral density (BMD) with Computerized Bone Mineralometry (CBM). RESULTS: Collected data demonstrated that only 35% of the subjects practiced physical activity during the week. BMI and percentage FM values were pathological in at least 50% of the population. On cardiological investigations (ECG and echocardiogram), no significant alterations were found. In all patients who performed CPET (79.4%), pathological values of the main functional capacity parameters were revealed, especially peak oxygen consumption (VO2 peak), even when corrected for BCM or FFM estimated at BIA and DEXA, respectively. In the CBM analysis, out of 27 patients in whom the femoral T-score was evaluated, a condition of osteopenia was revealed in 40.7% of the patients (11/27) and osteoporosis in 18.5% (5/27); out of 27 patients in whom the lumbar T-score was evaluated, 37% of the patients showed osteopenia (10/27) and 29.6% osteoporosis (8/27). When the comparison between exercising and non-exercising patients was performed, the only statistically significant difference that emerged was the median lumbar T-score value, which appeared lower in the group not performing physical activity (p = 0,009). CONCLUSIONS: The extensive cardiorespiratory evaluation, including CPET, of our cohort of spina bifida patients showed altered values of the main parameters related to cardiorespiratory fitness and is the only study in the literature that analysed bone mineralization values in physically active and sedentary spina bifida patients and demonstrated a statistically significant difference. Furthermore, it is the only study to date that investigated the possible association of congenital heart diseases with SD, without demonstrating the existence of pathological conditions.

The burden of chronic disease, multimorbidity, and polypharmacy in adults with Down syndrome.

Data on clinical characteristics of adults with Down syndrome (DS) are limited and the clinical phenotype of these persons is poorly described. This study aimed to describe the occurrence of chronic diseases and pattern of medication use in a population of adults with DS. Participants were 421 community dwelling adults with DS, aged 18 years or older. Individuals were assessed through a standardized clinical protocol. Multimorbidity was defined as the occurrence of two or more chronic conditions and polypharmacy as the concomitant use of five or more medications. The mean age of study participants was 38.3 ± 12.8 years and 214 (51%) were women. Three hundred and seventy-four participants (88.8%) presented with multimorbidity. The most prevalent condition was visual impairment (72.9%), followed by thyroid disease (50.1%) and hearing impairment (26.8%). Chronic diseases were more prevalent among participants aged >40 years. The mean number of medications used was 2.09 and polypharmacy was observed in 10.5% of the study sample. Psychotropic medications were used by a mean of 0.7 individuals of the total sample. The high prevalence of multimorbidity and the common use of multiple medications contributes to a high level of clinical complexity, which appears to be similar to the degree of complexity of the older non-trisomic population. A comprehensive and holistic approach, commonly adopted in geriatric medicine, may provide the most appropriate care to persons with DS as they grow into adulthood.

Interactions between drugs and geriatric syndromes in nursing home and home care: results from Shelter and IBenC projects.

AIM: Drugs may interact with geriatric syndromes by playing a role in the continuation, recurrence or worsening of these conditions. Aim of this study is to assess the prevalence of interactions between drugs and three common geriatric syndromes (delirium, falls and urinary incontinence) among older adults in nursing home and home care in Europe. METHODS: We performed a cross-sectional multicenter study among 4023 nursing home residents participating in the Services and Health for Elderly in Long-TERm care (Shelter) project and 1469 home care patients participating in the Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of community care (IBenC) project. Exposure to interactions between drugs and geriatric syndromes was assessed by 2015 Beers criteria. RESULTS: 790/4023 (19.6%) residents in the Shelter Project and 179/1469 (12.2%) home care patients in the IBenC Project presented with one or more drug interactions with geriatric syndromes. In the Shelter project, 288/373 (77.2%) residents experiencing a fall, 429/659 (65.1%) presenting with delirium and 180/2765 (6.5%) with urinary incontinence were on one or more interacting drugs. In the IBenC project, 78/172 (45.3%) participants experiencing a fall, 80/182 (44.0%) presenting with delirium and 36/504 (7.1%) with urinary incontinence were on one or more interacting drugs. CONCLUSION: Drug-geriatric syndromes interactions are common in long-term care patients. Future studies and interventions aimed at improving pharmacological prescription in the long-term care setting should assess not only drug-drug and drug-disease interactions, but also interactions involving geriatric syndromes.

A Case of Ralstonia pickettii Bloodstream Infection and the Growing Problem of Healthcare Associated Infections in Frail Older Adults.

Frailty is a clinically measurable state of vulnerability to developing increased dependency and/or mortality when exposed to a stressor. Chronic diseases, aggressive treatments, antibiotic overuse, microbiota changes, immune senescence, and increased use of medical devices and implants (i.e., central lines and catheters) expose modern patients to healthcare-associated infections (HAIs), multidrug-resistant bacteria, and new and unusual opportunistic pathogens. Older adults are among the main victims of HAIs and are associated with high costs, disability, morbidity, and mortality. Ralstonia pickettii is an emerging opportunistic pathogen that causes rare nosocomial infections in frail individuals. Herein, we present a case of bloodstream infection caused by R. pickettii in an 88-year-old woman with a relatively mild course. In addition to describing this unusual finding, this report discusses the problem of HAIs in older adults. Older age, comorbidities, and hospital admissions were among the main risk factors for HAIs. Adherence to guidelines, training, auditing, and surveillance is crucial for reducing the burden of HAIs in acute settings. Furthermore, avoiding incongruous hospitalizations would have positive implications both for preventing HAIs and improving patient quality of life.

Myocarditis in Athletes Recovering from COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: To assess the event rates of myocarditis detected by Cardiac Magnetic Resonance (CMR) in athletes who recovered from COVID-19. METHODS: A systematic literature search was performed to identify studies reporting abnormal CMR findings in athletes who recovered from COVID-19. Secondary analyses were performed considering increased serum high sensitivity troponin (hs-Tn) levels and electrocardiographic (ECG) and echocardiographic (ECHO) abnormalities. RESULTS: In total, 7988 athletes from 15 studies were included in the analysis. The pooled event rate of myocarditis was 1% (CI 1-2%), reaching 4% in the sub-group analysis. In addition, heterogeneity was observed (I2 43.8%). The pooled event rates of elevated serum hs-Tn levels, abnormal ECG and ECHO findings were 2% (CI 1-5%), 3% (CI 1-10%) and 2% (CI 1-6%), respectively. ECG, ECHO and serum hs-Tn level abnormalities did not show any correlation with myocarditis. CONCLUSIONS: The prevalence of COVID-19-related myocarditis in the athletic population ranges from 1 to 4%. Even if the event rate is quite low, current screening protocols are helpful tools for a safe return to play to properly address CMR studies. TRIAL REGISTRATION: the study protocol was registered in the PROSPERO database (registration number: CRD42022300819).

Predictors of Functional Decline in Nursing Home Residents: The Shelter Project.

BACKGROUND: The aim of our study was to identify independent predictors of functional decline in older nursing home (NH) residents, taking into account both resident and facility characteristics. METHODS: Longitudinal observational study involving 1,760 older (≥65 y) residents of NH participating in the SHELTER* study (57 NH in eight countries). All residents underwent a comprehensive geriatric assessment using the interRAI LTCF. Functional decline was defined as an increase of at least one point in the MDS Long Form ADL scale during a 1 year follow-up. Facility and country effects were taken into account. RESULTS: During the study period 891 (50.6%), NH residents experienced ADL decline. Residents experiencing ADL decline were older, had lower disability at baseline, were more frequently affected by severe dementia and by urinary incontinence, and used more antipsychotics. In the mixed-effect logistic regression model, factors independently associated with a higher risk of functional decline were dementia and urinary incontinence, whereas the presence of a geriatrician was a protective factor. CONCLUSIONS: Both resident and facility characteristics are associated with the risk of functional decline in NH residents. Increasing the quality of healthcare by involving a geriatrician in residents' care might be an important strategy to improve the outcome of this vulnerable population.

Deprescribing in Nursing Home Residents on Polypharmacy: Incidence and Associated Factors.

OBJECTIVES: To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe. DESIGN: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. SETTING: NHs in Europe and Israel. PARTICIPANTS: 1843 NH residents on polypharmacy. METHODS: Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months. RESULTS: Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing. CONCLUSIONS AND IMPLICATIONS: Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future.

Biomarkers for Sarcopenia: Reductionism vs. Complexity.

Sarcopenia, the progressive and generalized loss of muscle mass and strength/function, is a major health issue in older adults, given its high prevalence and burdensome clinical ramifications. The absence of a unified operational definition for sarcopenia has hampered its full appreciation by healthcare providers, researchers and policy-makers. At the same time, this unresolved debate and the complexity of musculoskeletal aging pose major challenges to the identification of clinically meaningful biomarkers. This review summarizes the current knowledge on biological markers for sarcopenia, including a critical appraisal of traditional procedures for biomarker development in the field of muscle aging. As an alternative approach, we illustrate the potential advantages of biomarker discovery procedures based on multivariate methodologies. Relevant examples of multidimensional biomarker modeling are provided with an emphasis on its clinical and research application.

The Relationship Between COPD and Frailty: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Frailty is common in seniors and is characterized by diminished physiological reserves and increased vulnerability to stressors. Frailty can change the prognosis and treatment approach of several chronic diseases, including COPD. The association between frailty and COPD has never been systematically reviewed. OBJECTIVES: The goal of this study was to conduct a systematic review and meta-analysis assessing the association of COPD with frailty and pre-frailty. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used when reporting this review. We searched PubMed, Web of Science, and Embase from January 1, 2002, to October 6, 2017. The quality of the studies was evaluated by using the Newcastle Ottawa Scale. Two assessors independently rated each study: scores > 7 were considered a low risk of bias; 5 to 7, a moderate risk of bias; and < 5, a high risk of bias. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I2) and publication bias were assessed. RESULTS: A total of 27 studies were selected: 23 cross-sectional, three longitudinal, and one both. The pooled prevalence of pre-frailty in individuals with COPD was 56% (95% CI, 52-60; I2 = 80.8%); it was 19% (95% CI, 14-24; I2 = 94.4%) for frailty. Patients with COPD had a two-fold increased odds of frailty (pooled OR, 1.97 [95% CI, 1.53-2.53]; I2 = 0.0%). Three longitudinal studies, presenting heterogeneous aims and methods, suggested a bidirectional association between COPD and frailty. CONCLUSIONS: Frailty and pre-frailty are common in individuals with COPD. Older subjects with COPD have a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in individuals with COPD and to further investigate any potential negative effects associated with the co-occurrence of these conditions. Longitudinal research that examines temporal associations between COPD and frailty are needed to further clarify this relationship and to assess if treatment of COPD may prevent the onset of frailty. TRIAL REGISTRY: PROSPERO registration No.: 58302; URL: https://www.crd.york.ac.uk/prospero/.

Circulating Mitochondrial DNA at the Crossroads of Mitochondrial Dysfunction and Inflammation During Aging and Muscle Wasting Disorders.

Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.

Association of Polypharmacy With 1-Year Trajectories of Cognitive and Physical Function in Nursing Home Residents: Results From a Multicenter European Study.

OBJECTIVES: To test the association between polypharmacy and 1-year change in physical and cognitive function among nursing home (NH) residents. DESIGN: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. SETTING: NH in Europe (n = 50) and Israel (n = 7). PARTICIPANTS: 3234 NH older residents. MEASUREMENTS: Participants were assessed through the interRAI long-term care facility instrument. Polypharmacy was defined as the concurrent use of 5 to 9 drugs and excessive polypharmacy as the use of ≥10 drugs. Cognitive function was assessed through the Cognitive Performance Scale (CPS). Functional status was evaluated through the Activities of Daily Living (ADL) Hierarchy scale. The change in CPS and ADL score, based on repeated assessments, was the outcome, and their association with polypharmacy was modeled via linear mixed models. The interaction between polypharmacy and time was reported [beta and 95% confidence intervals (95% CIs)]. RESULTS: A total of 1630 (50%) residents presented with polypharmacy and 781 (24%) excessive polypharmacy. After adjusting for potential confounders, residents on polypharmacy (beta 0.10, 95% CI 0.01-0.20) and those on excessive polypharmacy (beta 0.13, 95% CI 0.01-0.24) had a significantly higher decline in CPS score compared to those using <5 drugs. No statistically (P > .05) significant change according to polypharmacy status was shown for ADL score. CONCLUSIONS: Polypharmacy is highly prevalent among older NH residents and, over 1 year, it is associated with worsening cognitive function but not functional decline.

Bone-Muscle Crosstalk: Unraveling New Therapeutic Targets for Osteoporosis.

Osteoporosis is a condition featured by bone mass loss and bone tissue microarchitectural alterations due to impaired tissue homeostasis favoring excessive bone resorption versus deposition. The trigger of such an impairment and the downstream molecular pathways involved are yet to be clarified. The natural course of osteoporosis is particularly worrisome because, through a "silent" progression, it enhances bone fragility, increases the risk of fractures and is associated with increased risk of disability and mortality. To date, the assessment of bone mineral density by dual-energy X-ray absorptiometry, represents the non-invasive gold standard for the evaluation of bone mineralization and the diagnosis of osteoporosis. Although long known as a condition merely related to the hormonal-driven loss of bone homeostasis, emerging evidence supports the need of reframing osteoporosis in the context of structural and functional changes of the musculoskeletal system as a whole. Several age-related alterations of bone microenvironment and an altered bone-muscle crosstalk have been suggested to be relevant contributors to loss of bone strength and mass characterizing osteoporosis. The present work provides an overview of the current knowledge of the pathophysiology of osteoporosis obtained through advances in epigenetics, cell biology and osteoimmunology. In light of the increasingly recognized importance of bone-muscle interconnection, this review also discusses relevant pathways that may be dissected for identifying new therapeutic targets for age-related musculoskeletal degeneration.