Use of dried blood spots for monitoring inflammatory and nutritional biomarkers in the elderly.

OBJECTIVES: Blood microsampling, particularly dried blood spots (DBSs), is an attractive minimally-invasive approach that is well suited for home sampling and predictive medicine associated with longitudinal follow-up of the elderly. However, in vitro diagnostic quantification of biomarkers from DBS poses a major challenge. Clinical mass spectrometry can reliably quantify blood proteins in various research projects. Our goal here was to use mass spectrometry of DBS in a real-world clinical setting and compared it to the standard immunoassay method. We also sought to correlate DBS mass spectrometry measurements with clinical indices. METHODS: A clinical trial of diagnostic equivalence was conducted to compare conventional venous samples quantified by immunoassay and DBSs quantified by mass spectrometry in an elderly population. We assayed three protein biomarkers of nutritional and inflammatory status: prealbumin (transthyretin), C-reactive protein, and transferrin. RESULTS: The analysis of DBSs showed satisfactory variability and low detection limits. Statistical analysis confirmed that the two methods give comparable results at clinical levels of accuracy. In conclusion, we demonstrated, in a real-life setting, that DBSs can be used to measure prealbumin, CRP and transferrin, which are commonly used markers of nutritional status and inflammation in the elderly. However, there was no correlation with patient frailty for these proteins. CONCLUSIONS: Early detection and regular monitoring of nutritional and inflammatory problems using DBS appear to be clinically feasible. This could help resolve major public health challenges in the elderly for whom frailty leads to serious risks of health complications.

New Perspectives of Multiplex Mass Spectrometry Blood Protein Quantification on Microsamples in Biological Monitoring of Elderly Patients.

Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples quantification using mass spectrometry (MS) in a clinical setting by comparing two types of microsamples for multiplex MS protein detection. In a clinical trial based on elderly population, we compared 2 µL of plasma to dried blood spot (DBS) with a clinical quantitative multiplex MS approach. The analysis of the microsamples allowed the quantification of 62 proteins with satisfactory analytical performances. A total of 48 proteins were significantly correlated between microsampling plasma and DBS (p < 0.0001). The quantification of 62 blood proteins allowed us to stratify patients according to their pathophysiological status. Apolipoproteins D and E were the best biomarker link to IADL (instrumental activities of daily living) score in microsampling plasma as well as in DBS. It is, thus, possible to detect multiple blood proteins from micro-samples in compliance with clinical requirements and this allows, for example, to monitor the nutritional or inflammatory status of patients. The implementation of this type of analysis opens new perspectives in the field of diagnosis, monitoring and risk assessment for personalized medicine approaches.

Evaluation of mindfulness based stress reduction in symptomatic knee or hip osteoarthritis patients: a pilot randomized controlled trial.

BACKGROUND: To evaluate the efficacy for symptomatic knee and hip osteoarthritis (OA) patients of a mindfulness-based stress reduction (MBSR) program versus usual care. METHODS: Randomized, physician-blind, clinical trial in a monocentric prospective pilot study. Adult participants with symptomatic knee or hip OA were randomized into either intervention or control groups. The intervention group completed the MBSR program for a two-and-a-half-hour weekly session for 8 weeks. Usual care management was similar in both groups. All patients were evaluated at baseline, 3 months and 6 months. The primary objective was to evaluate the change in WOMAC pain score between baseline and 3 months in the MBSR group compared to usual care group. Secondary objectives were to evaluate changes in pain VAS, WOMAC scores, quality of life (SF-36), HAD scores between baseline and 3/6 months. RESULTS: Forty patients were enrolled in the study. No differences in the WOMAC pain score between the two groups were observed in the different time points. A similar pattern was found for the other assessment outcomes. However, a significant pain VAS reduction in favor of the MBSR group between baseline and 6 months (- 29.6 ± 26.6 vs - 9.3 ± 27.3; p = 0.03) has been reached. CONCLUSIONS: Our pilot RCT found contrasting results with no benefit on WOMAC pain and function and a delayed but long-term efficacy in pain VAS following a MBSR program in symptomatic knee or hip OA patients. Future studies with larger sample size are mandatory to confirm these preliminary results. Trial registration The study was registered in ClinicalTrials.gov (NCT03644615, 23/08/2018).

How to interpret cardiac biomarkers in renal failure and elderly?

New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn) as markers of injury while natriuretic peptides remain the markers of choice for myocardial dysfunction. However, variability extracardiac factors such as age, gender and renal function may alter circulating levels. In chronic kidney disease (CKD), the increase in circulating levels of these biomarkers in the absence of cardiac disease underlines the problem of discriminative value for diagnosis as well as the need to redefine the thresholds. In addition, these biomarkers are of potential interest to stratify cardiovascular risk, the leading cause of death in CKD. The aim of this work is to clarify the effect of age and renal function on circulating levels of high-sensitivity troponins and natriuretic peptides.

Estimation of age- and comorbidities-adjusted percentiles of high-sensitivity cardiac troponin T levels in the elderly.

BACKGROUND: Cardiac troponin level measured by high-sensitivity assays (hs-cTn) in the elderly is frequently found higher than the 99th percentile upper reference limit, making the diagnosis of acute coronary syndromes (ACS) difficult. This study aimed at: 1) identifying determinants of hs-cTnT levels in an unselected population of elderly subjects; and 2) assessing the prognosis value of increased hs-cTnT in elderly people free of ACS. METHODS: Hs-cTnT was measured in 591 individuals aged over 65 years without suspicion of ACS. Comorbidities were assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). C-reactive protein, α1-acid glycoprotein, albumin and creatinine were measured. Factors influencing hs-cTnT levels were assessed through linear regression and quantile regression was used to model percentiles of hs-cTnT. Risk of mortality was assessed through Cox regression. RESULTS: Age, gender, cardiac CIRS-G, estimated glomerular filtration rate (p<0.001 for all), albumin (p<0.028) and α1-acid glycoprotein (p=0.002) were independent predictors of hs-cTnT. After exclusion of outliers, the median was 15 ng/L and 99th percentile was 64 ng/L. After controlling for comorbidities, the 99th percentile increased from 24 ng/L at age 65 to 53 ng/L at age 90 in females and from 33 ng/L to 75 ng/L in males. In multivariate analysis, hs-cTnT level was significantly related to mortality. CONCLUSIONS: Hs-cTnT level is associated with inflammation and renal function in the elderly. Independently of comorbidities, hs-cTnT concentration increases exponentially with age after 65 years. Decision limits adapted to age and sex may be useful to patient management.

Frequency and severity of the dawn phenomenon in type 2 diabetes: relationship to age.

OBJECTIVE: To know whether age has an independent effect on the dawn phenomenon in noninsulin-using type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-one individuals with type 2 diabetes were matched for HbA(1c) and divided by age into three subgroups of 27 individuals (1: ≥70 years; 2: 60-69 years; and 3: ≤59 years). All underwent ambulatory continuous glucose monitoring for quantifying the dawn phenomenon (i.e., the absolute [∂G, mg/dL] or relative [∂G%] increments from nocturnal nadirs to prebreakfast time points). RESULTS: HbA(1c) levels and 24-h glycemic profiles were similar across the three groups. Glucose increments (mean ± SEM) were identical in the three groups: ∂G (mg/dL), 22.0 ± 4.7 (1), 21.3 ± 3.6 (2), and 18.0 ± 3.6 (3) and δG (%), 19.9 ± 4.9 (1), 21.6 ± 4.4 (2), and 17.6 ± 4.2 (3). Using the most common definition (∂G >10 mg/dL), the prevalence of the dawn phenomenon was 52, 70, and 59% in groups 1, 2, and 3, respectively. CONCLUSIONS: The dawn phenomenon is present in the elderly.

Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults.

BACKGROUND: Physical performance measured by gait speed is being recognized as a major instrument for clinical evaluation in older adults, because it predicts physical frailty, loss of autonomy, hospitalization and decreased survival. Low-grade chronic inflammation and oxidative stress, mediated partly by the superoxide anion produced by NADPH oxidase, are closely linked and could be involved in age-related physical decline. OBJECTIVE: To determine whether slow gait speed is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation. DESIGN AND SETTING: Observational study among the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 ± 6.1 years old). METHODS: Gait speed was evaluated by walking at self-chosen usual pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method. Inflammation was evaluated by CRP, fibrinogen and leukocyte count. RESULTS: Among the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow walkers) and 101 (36.1%) with a gait speed ≥ 0.8 m/s. Superoxide production and inflammation markers, such as fibrinogen, were more important in slow walkers (p = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion overproduction and fibrinogen were independently associated with physical frailty assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). CONCLUSION: Physical frailty in older people is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.

Serotonin syndrome during treatment with low dose of escitalopram associated with miconazole mucoadhesive tablet: a suspected drug interaction.

Antidepressant treatments, including selective serotonin reuptake inhibitors, are associated in older adults with an increased risk of adverse effects compared to younger adults. This is partly explained by multiple drug use causing drug-drug interactions. In the present report, we describe a case of serotonin syndrome in an 88-year-old woman receiving a low dose of escitalopram. The onset of this episode could have been induced by a drug-drug interaction with an acute treatment by miconazole gingival adhesive tablets. The lack of pharmacokinetic data in the elderly population should prompt us to be especially cautious about prescription of this new formulation of miconazole in association with drugs metabolized by cytochromes P450 isoenzymes.