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Background: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents. Objective: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality. Method: This is a cross-sectional study of 1,094 older people residing in 6 nursing homes in Flanders (Belgium) between March 1, 2020 and May 30, 2020. We considered all residents who were taking statins for at least 5 days as statin users. All-cause mortality during the 3 months of data collection was the primary outcome. Propensity score overlap-weighted logistic regression models were applied with age, sex, functional status, diabetes, and cardiac failure/ischemia as potential confounders. Results: 185 out of 1,094 residents were on statin therapy (17%). The statin intake was associated with decreased all-cause mortality: 4% absolute risk reduction; adjusted odds ratio 0.50; CI 0.31–0.81, p = 0.005. Conclusions: The statin intake was associated with decreased all-cause mortality in older people residing in nursing homes. More in-depth studies investigating the potential geroprotector effect of statins in this population are needed. [ABSTRACT FROM AUTHOR]

Objective: One of the greatest challenges in clinical trial design is dealing with the subjectivity and variability introduced by human raters when measuring clinical end-points. We hypothesized that robotic measures that capture the kinematics of human movements collected longitudinally in patients after stroke would bear a significant relationship to the ordinal clinical scales and potentially lead to the development of more sensitive motor biomarkers that could improve the efficiency and cost of clinical trials. Materials and methods: We used clinical scales and a robotic assay to measure arm movement in 208 patients 7, 14, 21, 30 and 90 days after acute ischemic stroke at two separate clinical sites. The robots are low impedance and low friction interactive devices that precisely measure speed, position and force, so that even a hemiparetic patient can generate a complete measurement profile. These profiles were used to develop predictive models of the clinical assessments employing a combination of artificial ant colonies and neural network ensembles. Results: The resulting models replicated commonly used clinical scales to a cross-validated R2 of 0.73, 0.75, 0.63 and 0.60 for the Fugl-Meyer, Motor Power, NIH stroke and modified Rankin scales, respectively. Moreover, when suitably scaled and combined, the robotic measures demonstrated a significant increase in effect size from day 7 to 90 over historical data (1.47 versus 0.67). Discussion and conclusion: These results suggest that it is possible to derive surrogate biomarkers that can significantly reduce the sample size required to power future stroke clinical trials. [ABSTRACT FROM AUTHOR]

Liver enzyme concentrations are measured as safety end points in clinical trials to detect drugrelated hepatotoxicity, but little is known about the epidemiology of these biomarkers in subjects without hepatic dysfunction who are enrolled in drug trials. We studied alanine and aspartate aminotransferase (ALT and AST) in subjects randomized to placebo who completed assessments over 36 mo in a cardiovascular outcome trial [the Stabilisation of Atherosclerotic Plaque by Initiation of Darapladib Therapy ("STABILITY") trial; n = 4,264; mean age: 64.2 yr] or over 12 mo in three trials that enrolled only subjects with type 2 diabetes (T2D) [the DIA trials; n = 308; mean age: 62.4 yr] to investigate time-dependent relationships and the factors that might affect ALT and AST, including body mass index (BMI), T2D, and renal function. Multivariate linear mixed models examined time-dependent relationships between liver enzyme concentrations as response variables and BMI, baseline T2D status, hemoglobin A1c levels, and renal function, as explanatory variables. At baseline, ALT was higher in individuals who were men, >65 yr old, and obese and who had glomerular filtration rate (GFR) <60 ml·min-1·1.73 m-2. ALT was not significantly associated with T2D at baseline, although it was positively associated with HbA1c. GFR had a greater impact on ALT than T2D. ALT concentrations decreased over time in subjects who lost weight but remained stable in individuals with increasing BMI. Weight change did not alter AST concentrations. We provide new insights on the influence of time, GFR, and HbA1c on ALT and AST concentrations and confirm the effect of sex, age, T2D, BMI, and BMI change in subjects receiving placebo in clinical trials. [ABSTRACT FROM AUTHOR]

The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes. [ABSTRACT FROM AUTHOR]

Considers how ambulatory blood pressure (ABP) monitoring is used increasingly in clinical practice. How it affects treatment of blood pressure which has not been determined; Study which compares conventional blood pressure measurement and ABP measurement in the management of hypertensive patients; Design; Setting; Participants; Interventions; Main outcome measures; Results; Conclusions.

Among the drugs used to manage hypertension and diabetes mellitus are angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins, all of which are known to improve endothelial dysfunction [[1]]. Furthermore, the National Institutes of Health COVID-19 Treatment Guidelines recommend that patients who are already taking statins for the treatment or prevention of cardiovascular disease should continue statin treatment if they develop COVID-19 [[18]]. The interaction between obesity, cardiometabolic disorders and COVID-19 represents a syndemic that requires both social intervention and a multipharmacological approach. [Extracted from the article]