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Beta‐blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age‐related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta‐blockers are associated with an increased risk of falls in older beta‐blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta‐blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B‐PROOF cohort. The associations between the beta‐blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p =.01). No association was found for nonselective beta‐blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta‐blockers users. This might be caused by a decreased β1‐selectivity in high plasma concentrations. In the future, beta‐blocker concentrations could potentially help clinicians estimate fall risk in older beta‐blockers users and personalize treatment. [ABSTRACT FROM AUTHOR]

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Contrast-enhanced ultrasound is an imaging technique that can be used to quantify microvascular blood volume and blood flow of vital organs in humans. It relies on the use of microbubble contrast agents and ultrasound-based imaging of microbubbles. Over the past decades, both ultrasound contrast agents and experimental techniques to image them have rapidly improved, as did experience among investigators and clinicians. However, these improvements have not yet resulted in uniform guidelines for CEUS when it comes to quantification of tissue perfusion in humans, preventing its uniform and widespread use in research settings. The objective of this review is to provide a methodological overview of CEUS and its development, the influences of hardware and software settings, type and dosage of ultrasound contrast agent, and method of analysis on CEUS-derived perfusion data. Furthermore, we will discuss organ-specific imaging challenges, advantages, and limitations of CEUS., (© 2019 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Aims: In type 2 diabetes impaired insulin-induced muscle perfusion is thought to contribute to reduced whole-body glucose uptake. In this study, we examined the effects of iloprost, a stable prostacyclin analogue, on insulin-induced muscle capillary recruitment and whole-body glucose uptake., Materials and Methods: In a randomized cross-over design, 12 type 2 diabetes patients (age, 55 [46-69] years; BMI, 33.1 [31.0-39] kg/m 2 ) underwent two hyperinsulinaemic-euglycaemic clamps, one with and one without simultaneous low-dose iloprost infusion. Contrast-enhanced ultrasonography of the vastus lateralis muscle was performed before and during the clamp. Muscle capillary recruitment was calculated as percentage change in microvascular blood volume (MBV) before and during the clamp., Results: Insulin infusion reduced skeletal muscle MBV by ~50% compared to the fasting state (fasting, 1.77·10 -4 [1.54·10 -5 -2.44·10 -3 ] arbitrary units (AU); hyperinsulinaemia, 6.69·10 -5 [2.68·10 -6 -5.72·10 -4 ] AU; P = 0.050). Infusion of iloprost prevented this insulin-induced skeletal muscle capillary derecruitment, from (-49.5 [-89.5 to 55.3] %) to (8.0 [-68.8 to 306.6] %), for conditions without and with iloprost, respectively. The rate of glucose disappearance (R d ) did not change significantly during iloprost infusion (17.3 [10.0-40.8] μmol/kg/min) compared with insulin infusion alone (17.6 [9.9-68.7] μmol/kg/min)., Conclusions: Our data suggest that acute improvement in insulin-stimulated muscle perfusion is not an attractive therapeutic approach to bypass cellular resistance to glucose uptake in type 2 diabetes. Whether long-term improvements in insulin-induced muscle perfusion may prove beneficial for glucose disposal remains to be determined., (© 2018 John Wiley & Sons Ltd.)