Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging

Objectives: Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. / Methods: We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. / Results: Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). / Conclusions: Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore

Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study

Introduction: Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. Methods: The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. Results: Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. Conclusion: Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments

Clinical narrative analytics challenges

Precision medicine or evidence based medicine is based on the extraction of knowledge from medical records to provide individuals with the appropriate treatment in the appropriate moment according to the patient features. Despite the efforts of using clinical narratives for clinical decision support, many challenges have to be faced still today such as multilinguarity, diversity of terms and formats in different services, acronyms, negation, to name but a few. The same problems exist when one wants to analyze narratives in literature whose analysis would provide physicians and researchers with highlights. In this talk we will analyze challenges, solutions and open problems and will analyze several frameworks and tools that are able to perform NLP over free text to extract medical entities by means of Named Entity Recognition process. We will also analyze a framework we have developed to extract and validate medical terms. In particular we present two uses cases: (i) medical entities extraction of a set of infectious diseases description texts provided by MedlinePlus and (ii) scales of stroke identification in clinical narratives written in Spanish

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study

Background: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. Research design and methods: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. Results: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumabtreated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. Conclusions: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins

The effects of a muscle resistance program on the functional capacity, knee extensor muscle strength and plasma levels of IL-6 and TNF-α in pre-frail elderly women: a randomized crossover clinical trial - a study protocol

<p>Abstract</p> <p>Background</p> <p>With the increase in the elderly population, a growing number of chronic degenerative diseases and a greater dependency on caregivers have been observed. Elderly persons in states of frailty remain more susceptible to significant health complications. There is evidence of an inverse relationship between plasma levels of inflammatory mediators and levels of functionality and muscle strength, suggesting that muscle-strengthening measures can aid in inflammatory conditions. The purpose of this study will be verified the effect of a muscle-strengthening program with load during a ten-week period in pre-frail elderly women with attention to the following outcomes: (1) plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), (2) functional capacity and (3) knee extensor muscle strength.</p> <p>Methods/Design</p> <p>The study design is a randomized crossover clinical trial evaluating 26 elderly women (regardless of their race and/or social condition) who are community residents, older than 65, and classified as pre-frail according to the criteria previously described by Fried et al. (2004). All subjects will be assessed using the Timed up and go and 10-Meter Walk Test functional tests. The plasma levels of IL-6 and TNF-α will be assessed by ELISA (<it>enzyme-linked immunosorbent assay</it>) with high sensitivity kits (Quantikine^®HS, R&D Systems Minneapolis, MN, U.S.). Knee extensor muscle strength will be assessed using the <it>Byodex System 3 Pro</it>^{<it>® </it>}isokinetic dynamometer at angular speeds of 60 and 180°/s. The intervention will consist of strengthening exercises of the lower extremities at 50 to 70% of 1RM (maximal resistance) three times per week for ten weeks. The volunteers will be randomized into two groups: group E, the intervention group, and group C, the control group that did not initiate any new activities during the initial study period (ten weeks). After the initial period, group C will begin the intervention and group E will maintain everyday activities without exercising. At the end of the total study period, all volunteers will be reassessed.</p> <p>Discussion</p> <p>To demonstrate and discuss possible influences of load-bearing exercises on the modification of plasma levels of IL-6 and TNF-α and in the functional performance of pre-frail elderly women.</p> <p>Trial Registration</p> <p>ISRCTN62824599</p