The role of prognostic stratification on prescription of anticoagulants in older patients with atrial fibrillation : a multicenter, observational, prospective European study (EUROSAF)

Background: Literature suggests that different risks of mortality could influence physicians in prescribing or not anticoagulants in older patients with atrial fibrillation (AF). The Multidimensional Prognostic Index (MPI) can be considered a tool for the detection of multidimensional frailty. The aim of this cross-sectional study was to evaluate whether prescription patterns of oral anticoagulants exist, based on MPI values. Methods: Older hospitalised patients (age >= 65 years) with non-valvular AF were included across 24 European centres. MPI was calculated using validated and standardised tools derived from a comprehensive geriatric assessment. Other functional and clinical information were collected to calculate indexes specific for haemorrhagic and thromboembolic risk in AF. Results: Altogether, 2,012 participants affected by AF (mean age was 83.2 +/- 7.5, range: 65-104 years), with a higher presence of women (57.0%), were included. Overall, 440 took vitamin K antagonists VKAs (22.0%), 667 (33.4%) direct oral anticoagulants (DOACs), whilst 44.6% did not take any anticoagulant treatment. Prescription of anticoagulants was associated with MPI values, with people taking anticoagulants having lower mean MPI values. Anticoagulant therapy was not used in 53.1% of the group with the highest risk of mortality, compared with 32.3% of those in the group with the lowest mortality risk. People with higher scores in MPI were less frequently treated with anticoagulant therapy, after adjusting for several potential confounders. Conclusions: The EURopean study of Older Subjects with Atrial Fibrillation (EUROSAF) suggested that almost half of the older persons with AF do not receive anticoagulants and that MPI is an important determinant in prescribing or not anticoagulants.Peer reviewe

Multidimensional prognostic index and the risk of fractures: an 8-year longitudinal cohort study in the Osteoarthritis Initiative

Summary: In this longitudinal study, with a follow-up of 8 years, multidimensional prognostic index (MPI), a product of the comprehensive geriatric assessment, significantly predicted the onset of fractures in older people affected by knee osteoarthritis. Purpose: Frailty may be associated with higher fracture risk, but limited research has been carried out using a multidimensional approach to frailty assessment and diagnosis. The present research aimed to investigate whether the MPI, based on comprehensive geriatric assessment (CGA), is associated with the risk of fractures in the Osteoarthritis Initiative (OAI) study. Methods: Community-dwellers affected by knee OA or at high risk for this condition were followed-up for 8 years. A standardized CGA including information on functional, nutritional, mood, comorbidity, medication, quality of life, and co-habitation status was used to calculate the MPI. Fractures were diagnosed using self-reported information. Cox’s regression analysis was carried out and results are reported as hazard ratios (HRs), with their 95% confidence intervals (CIs), adjusted for potential confounders. Results: The sample consisted of 4024 individuals (mean age 61.0 years, females = 59.0%). People with incident fractures had a significant higher MPI baseline value than those without (0.42 ± 0.18 vs. 0.40 ± 0.17). After adjusting for several potential confounders, people with an MPI over 0.66 (HR = 1.49; 95%CI: 1.11–2.00) experienced a higher risk of fractures. An increase in 0.10 point in MPI score corresponded to an increase in fracture risk of 4% (HR = 1.04; 95%CI: 1.008–1.07). Higher MPI values were also associated with a higher risk of non-vertebral clinical fractures. Conclusion: Higher MPI values at baseline were associated with an increased risk of fractures, reinforcing the importance of CGA in predicting fractures in older people affected by knee OA. © 2021, The Author(s)

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta-analysis.

INTRODUCTION Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI-LB set out in the criteria. METHODS MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI-LB. RESULTS Fifty-seven articles were included. The meta-analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta-iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. DISCUSSION The available evidence largely supports the current diagnostic criteria for MCI-LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. HIGHLIGHTS A meta-analysis of the diagnostic features of MCI-LB was carried out. The four core clinical features were more common in MCI-LB than MCI-AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI-LB. More evidence is needed for the proposed biomarkers. FDG-PET and quantitative EEG show promise as diagnostic biomarkers in MCI-LB

Long-term unsupervised mobility assessment in movement disorders

Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them

Differences Between Plasma and Cerebrospinal Fluid p-tau181 and p-tau231 in Early Alzheimer's Disease

Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer's disease (AD) pathology. In this cross-sectional study including 91 subjects, plasma and cerebrospinal fluid (CSF) p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD. Plasma p-tau231 and p-tau181 were strongly related to CSF phosphorylated tau, total tau and amyloid and exhibited a high accuracy-close to CSF p-tau231 and p-tau181-to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings

Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase.

The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1

Inequality in provider continuity for children by Australian general practitioners

<p>Abstract</p> <p>Background</p> <p>There is little published on provider continuity in Australian general practice and none on its effect on inequality of care for children.</p> <p>Method</p> <p>Questionnaire administered to parents of the ACT Kindergarten Health Screen asking the name of their child's usual GP and practice address between 2001 and 2008.</p> <p>Results</p> <p>Parents of 30,789 children named 433 GPs and 141 practices. In each year, an average of 77% of parents could name both the GP and the practice, an average of 11% of parents could name only the practice, and an average of 12% of parents could name neither. In each year, 25% of parents could not name a usual GP for children of Aboriginal or Torres Straight Islander descent, or children born outside of Australia, compared to 10% of all other children (p = < 0.0001). The frequency of GPs displaying continuity of care varied over time with 19% of GPs being present in the ACT in only one year and 39% of GPs being present in every year over the eight years of study. GPs displayed two different forms of transience either by working in more than one practice in each year (5% of GPs), or by not being present in the ACT region from one year to the next (15% of GPs). Fewer parents nominated transient GPs as their child's GP compared to choosing GPs who displayed continuity (p < 0.001).</p> <p>Conclusions</p> <p>Many GPs (39%) were reported to provide continuity of care for in the ACT region and some GPs (20%) displayed transient care. Indigenous children or children born outside of Australia had less equity of access to a nominated GP than all other children. Such inequity might disappear if voluntary registration of children was adopted in Australian general practice.</p

Plasma Cystatin C correlates with plasma NfL levels and predicts disease progression in Parkinson's disease

INTRODUCTION: Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration and clinical progression in a longitudinal study. METHODS: Plasma Cys-C, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6) and Neurofilament Light Chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration and peripheral inflammation. RESULTS: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at two years of follow-up independently from the peripheral inflammatory profile. CONCLUSIONS: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases

Etiological research in pediatric multiple sclerosis: A tool to assess environmental exposures (PEDiatric Italian Genetic and enviRonment ExposurE Questionnaire)

Background: The etiology of pediatric-onset multiple sclerosis is unknown although putative genetic and environmental factors appear to be involved. Among children multiple sclerosis onset occurs closer to the susceptibility window thank in adults and the exposure to etiological environmental factors is more informative. An Italian multicentre case-control study (the PEDiatric Italian Genetic and enviRonment ExposurE, PEDIGREE study) was designed to investigate environmental exposures in pediatric-onset multiple sclerosis and their interaction with genetics. Objectives: To collect evidence on exposures to environmental risk factors in pediatric-onset multiple sclerosis, a questionnaire was developed for the Italian population (PEDIGREE Questionnaire) and is presented. Methods: PEDIGREE Questionnaire develops from an existing tool used in case-control studies on pediatric-onset multiple sclerosis in US Americans, and was translated, adapted and tested for the contents perceived relevance, acceptability, feasibility and reliability in a population of Italian pediatric subjects and their parents recruited from clinics and general population. Results: PEDIGREE Questionnaire contents were overall deemed relevant by the study population, acceptable for 100% participants and feasible for at least 98%. PEDIGREE Questionnaire degree of reliability ranged 56% to 72%. Conclusion: PEDIGREE Questionnaire proves to be an efficient tool to assess environmental exposures in the Italian pediatric population. We encourage the dissemination of population-specific questionnaires and shared methodology to optimize efforts in MS etiological research

Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials