Type 2 diabetes mellitus (T2DM) is a leading cause of disability globally. Frailty is a high-impact geriatric condition that increases the risk of negative health outcomes and imposes remarkable ...health and social burden. Both frailty and T2DM show multifaceted pathophysiology, phenotypic heterogeneity, and fluctuating manifestations that challenge their management, especially when the two conditions co-occur. Muscle wasting and its correlates (e.g., metabolic perturbations and functional decline) that underlie frailty may exacerbates clinical manifestations of T2DM in older people, resulting in worse prognosis. The intrinsic complexity of frailty and T2DM has hampered the identification of clinically meaningful biomarkers to track the clinical progression of the two conditions over time and to monitor the efficacy of pharmacological and lifestyle interventions. Here, we propose an innovative approach for biomarker identification that couples multi-platform analytical determinations with chemometric modeling strategies. This novel multi-marker discovery process is described in the context of the “Metabolic biomarkers of frailty in older people with type 2 diabetes mellitus” (MetaboFrail) study that aimed at identifying metabolic biomarkers of frailty in functionally limited older persons with T2DM.
•Frailty and type 2 diabetes (T2DM) are prevalent high-impact condition in older adults.•Muscle wasting and functional decline that underlie frailty may exacerbate clinical manifestations in older people with T2DM.•The complexity of frailty in T2DM should be approached through a multi-marker strategy.•MetaboFrail proposes a novel biomarker discovery process for frailty in T2DM.
Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, ...including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions.
Objectives
To describe NSAID utilization for musculoskeletal conditions in a large cohort of Italian elderly with cerebro/cardiovascular disease, a population in which NSAIDs should be generally ...avoided due to the prothrombotic potential.
Methods
Administrative data from five Italian geographic areas were analyzed. Patients aged ≥ 65 with a cerebro/cardiovascular event recorded between 2008 and 2011 (cohort entry) were selected. Prescription NSAIDs reimbursed for musculoskeletal conditions and dispensed during 1 year follow-up were retrieved to describe (i) prevalence of use, (ii) average amount of defined daily doses of NSAIDs claimed by users per day of follow-up, and (iii) distribution of the received daily dose (RDD) among patients with ≥ 2 dispensings. Among new users, i.e., patients without NSAID dispensings during 2 years before cohort entry, the first dispensed NSAID molecule was observed.
Results
Overall, 511,989 patients were selected. Across the five geographic areas, prevalence of use ranged from 48 to 21% and average consumption ranged between 30 and 67 DDD/1000 users/day. Around 10% of patients in the overall cohort had a RDD > 1. Nimesulide (9.6%) and diclofenac (7.5%) had the highest prevalence of use. The most consumed NSAIDs were nimesulide and coxibs with 10.6 and 7.5 DDD/1000 users/day, respectively. Among new users recruited in 2011, 30% had diclofenac or a coxibs as the first prescription.
Conclusions
NSAID use was common in the study cohort, particularly in central-southern areas. In contrast with current recommendations, coxibs and diclofenac were among the most prescribed active principles, even in new users. Interventions to promote appropriateness of use are warranted.
Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that ...expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.
Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD).
A cohort study was conducted ...using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug-drug interactions. Outcome occurrence was evaluated 180 days after AP initiation.
Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27-1.39) for conventional APs. There was no increased mortality risk with single drug-drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00-1.67)).
Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.
BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better ...adherence to antidepressant therapy may reduce mortality.
The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates.
Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3-14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (- 1-38), 14% (7-20), 20% (13-26) and 13% (7-19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively.
Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.
Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This ...study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention.
Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models.
Compared to past users, current CCB users had significant reductions in risks of CV events OR 0.88 (95% CI: 0.84-0.91), hospitalization 0.90 (0.88-0.93) and mortality 0.48 (0.47-0.49). Current users of long-acting dihydropyridines (DHPs) had the lowest risk OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality, whereas current users of short-acting CCBs had an increased risk of acute CV events OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs and hospitalizations OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42).
The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.
Chronic, low-grade inflammation and declining physical function are hallmarks of the aging process. However, previous attempts to correlate individual inflammatory biomarkers with physical ...performance in older people have produced mixed results. Given the complexity of the inflammatory response, the simultaneous analysis of an array of inflammatory mediators may provide more insights into the relationship between inflammation and age-related physical function decline. This study was designed to explore the association between a panel of inflammatory markers and physical performance in older adults through a multivariate statistical approach.
Community-dwelling older persons were categorized into "normal walkers" (NWs; n = 27) or "slow walkers" (SWs; n = 11) groups using 0.8 m s(-1) as the 4-m gait speed cutoff. A panel of 14 circulating inflammatory biomarkers was assayed by multiplex analysis. Partial least squares-discriminant analysis (PLS-DA) was used to identify patterns of inflammatory mediators associated with gait speed categories.
The optimal complexity of the PLS-DA model was found to be five latent variables. The proportion of correct classification was 88.9% for NW subjects (74.1% in cross-validation) and 90.9% for SW individuals (81.8% in cross-validation). Discriminant biomarkers in the model were interleukin 8, myeloperoxidase, and tumor necrosis factor alpha (all higher in the SW group), and P-selectin, interferon gamma, and granulocyte-macrophage colony-stimulating factor (all higher in the NW group).
Distinct profiles of circulating inflammatory biomarkers characterize older subjects with different levels of physical performance. The dissection of these patterns may provide novel insights into the role played by inflammation in the disabling cascade and possible new targets for interventions.
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