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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.)

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., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Inappropriate polypharmacy is highly prevalent among older adults and presents a significant healthcare concern. Conducting medication reviews and implementing deprescribing strategies in multimorbid older adults with polypharmacy are an inherently complex and challenging task. Recognizing this, the Special Interest Group on Pharmacology of the European Geriatric Medicine Society has compiled evidence on medication review and deprescribing in older adults and has formulated recommendations to enhance appropriate prescribing practices. The current evidence supports the need for a comprehensive and widespread transformation in education, guidelines, research, advocacy, and policy to improve the management of polypharmacy in older individuals. Furthermore, incorporating deprescribing as a routine aspect of care for the ageing population is crucial. We emphasize the importance of involving geriatricians and experts in geriatric pharmacology in driving, and actively participating in this transformative process. By doing so, we can work towards achieving optimal medication use and enhancing the well-being of older adults in the generations to come., (© 2023. The Author(s).)

Purpose: The aim of this clinical review was to summarise the existing knowledge on fall risk associated with benzodiazepines (BZDs) and Z-drugs in older people with focus on appropriate prescribing, including deprescribing., Methods: We conducted a literature search in June 2021 in PubMed and Embase with citation and reference checking. Personal reference libraries and international websites were also used. Keywords for the searches included "benzodiazepines", "Z-drugs", "falls", "deprescribing", "fall-risk-increasing-drugs", "inappropriate prescribing", "older people" and matching synonyms. We discuss use of BZDs and Z-drugs, potential fall-related adverse reactions, alternatives for and deprescribing of BZDs and Z-drugs in older persons., Results: BZDs and Z-drugs differ in fall-related adverse effect profile. They contribute to fall risk through orthostatic hypotension, dizziness and/or imbalance, sedation, muscular weakness, ataxia, etc. Fall incidents contribute significantly to mortality and morbidity. Therefore, there is a need for appropriate prescribing and use of BZDs and Z-drugs in older people. In practice, this means pertaining to a strict indication, strongly consider to non-pharmacological alternatives, limit use to the lowest dose and the shortest duration possible. Judicious deprescribing should be considered and encouraged as well. Practical resources, tools and algorithms are available to guide and assist clinicians in deprescribing BZDs and Z-drugs., Conclusions: Prescribing BZDs and Z-drugs should be done in a well-considered way in fall-prone older people. A good overview and insight in the fall-related adverse effects of these drugs, as well as the availability of different strategies to increase the appropriate use, including deprescribing initiatives, can assist clinicians in clinical decision-making., (© 2022. The Author(s).)

Purpose: The aim of this clinical narrative review was to summarise the existing knowledge on the use of anticoagulants and potential adverse events in older people at risk of falls with a history of atrial fibrillation or venous thromboembolism. The review also offers practical steps prescribers can take when (de-)prescribing anticoagulants to maximise safety., Methods: Literature searches were conducted using PubMed, Embase and Scopus. Additional articles were identified by searching reference lists., Results: Anticoagulants are often underused in older people due to concerns about the risk of falls and intracranial haemorrhage. However, evidence suggests that the absolute risk is low and outweighed by the reduction in stroke risk. DOACs are now recommended first line for most patients due to their favourable safety profile. Off-label dose reduction of DOACs is not recommended due to reduced efficacy with limited reduction in bleeding risk. Medication review and falls prevention strategies should be implemented before prescribing anticoagulation. Deprescribing should be considered in severe frailty, limited life expectancy and increased bleeding risk (e.g., cerebral microbleeds)., Conclusion: When considering whether to (de-)prescribe anticoagulants, it is important to consider the risks associated with stopping therapy in addition to potential adverse events. Shared decision-making with the patient and their carers is crucial as patient and prescriber views often differ., (© 2023. The Author(s).)

Purpose: Advancing age, declining health status, and a shift in benefit/risk balance warrant judicious use of preventive medications in older persons, including consideration of deprescribing. Lack of guidance on deprescribing is a major barrier for prescribers to consider deprescribing in daily practice. The aim of this review was to evaluate to what extent osteoporosis guidelines include bisphosphonate deprescribing recommendations., Methodology: We conducted a systematic review, searching PubMed, Embase, and grey literature. We included guidelines on treatment of osteoporosis with bisphosphonates. Two independent reviewers screened titles, abstracts, and full texts. Recommendations for deprescribing were extracted, and quality of guidelines were assessed., Results: Among 9345 references, 42 guidelines were included. A total of 32 (76%) guidelines included deprescribing recommendations: 29 (69%) guidelines included non-specific deprescribing recommendations framed as a drug holiday, of which 2 (5%) also included specific deprescribing recommendations based on individual health context (e.g. life expectancy, frailty, function, preferences/goals). Twenty-four (57%) guidelines included practical deprescribing recommendations, and 27 (64%) guidelines included recommendations for when deprescribing should not be considered., Conclusion: Bisphosphonate deprescribing recommendations in osteoporosis guidelines were primarily framed as drug holidays, with limited guidance on how to make individualized deprescribing decisions based on individual health context. This suggests a need for additional focus on deprescribing in osteoporosis guidelines., (© 2023. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Purpose: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users., Methods: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders., Results: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk., Conclusion: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed., (© 2023. The Author(s).)

The number of people living with dementia, such as Alzheimer's disease, is increasing worldwide. Persons with dementia often have a high risk of atherosclerotic cardiovascular disease and they are therefore theoretically eligible for treatment of hypertension and hyperlipidemia. However, in this population, beneficial and harmful effects of cardiovascular risk management (CVRM) may be different compared to older persons without cognitive impairment. Current CVRM guidelines are based on trials from which persons with dementia were excluded. In this narrative review, we will discuss how current guidelines can be translated to persons with dementia and which aspects should be taken into account when treating hypertension and hyperlipidemia to prevent major adverse cardiovascular events (MACE). Survival time is significantly shorter in persons with dementia. We therefore suggest that since the main goal of CVRM is prevention of MACE, first of all, the patient's life expectancy and treatment wishes should be evaluated. Risk assessment tools are to be used with care, as they tend to overestimate the 5- and 10-year risk of MACE and benefit from CVRM in the prevention of MACE in persons with dementia. When the clinician and patient have decided that treatment is initiated or intensified, patients should be closely monitored since they are at high risk for adverse drugs events and overtreatment due to the natural course of blood pressure in persons with dementia. In the event of intolerance or side effects, medication should be switched or withdrawn. For persons with dementia and limited life expectancy, deprescribing should be part of usual care.

Purpose: The aim of this clinical review was to summarize the existing knowledge on fall risk associated with antidepressant use in older adults, describe underlying mechanisms, and assist clinicians in decision-making with regard to (de-) prescribing antidepressants in older persons., Methodology: We comprehensively examined the literature based on a literature search in Pubmed and Google Scholar, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in depression in geriatric patients. We discuss use of antidepressants, potential fall-related side effects, and deprescribing of antidepressants in older persons., Results: Untreated depression and antidepressant use both contribute to fall risk. Antidepressants are equally effective, but differ in fall-related side effect profile. They contribute to (or cause) falling through orthostatic hypotension, sedation/impaired attention, hyponatremia, movement disorder and cardiac toxicity. Falling is an important driver of morbidity and mortality and, therefore, requires prevention. If clinical condition allows, withdrawal of antidepressants is recommended in fall-prone elderly persons. An important barrier is reluctance of prescribers to deprescribe antidepressants resulting from fear of withdrawal symptoms or disease relapse/recurrence, and the level of complexity of deprescribing antidepressants in older persons with multiple comorbidities and medications. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antidepressants., Conclusions: (De-) prescribing antidepressants in fall-prone older adults is often challenging, but detailed insight in fall-related side effect profile of the different antidepressants and a recently developed expert-based decision aid STOPPFalls assists prescribers in clinical decision-making.

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.)

Background/objectives: Epidemiological, in vitro and animal studies suggest that grape polyphenols, such as those present in wine, have favorable effects on the metabolic syndrome. However, controversy remains whether treatment with grape polyphenols is effective in humans. Here, we aimed to systemically review the effects of grape polyphenols on metabolic syndrome components in humans., Subjects/methods: We systematically searched Medline, EMBASE and the Cochrane database for all clinical trials assessing the effects of grape polyphenols on insulin sensitivity, glycemia, blood pressure or lipid levels. We screened all titles and reviewed abstracts of potentially relevant studies. Full papers were assessed for eligibility and quality-rated according to the Jadad scale by two independent assessors., Results: Thirty-nine studies met the eligibility criteria. In individuals without component criteria of the metabolic syndrome, only low- and medium-quality studies were found with primarily neutral results. In individuals with the metabolic syndrome or related conditions, one of two high-quality studies suggested improvement in insulin sensitivity. Glycemia was improved in 2 of 11 lower-quality studies and 2 of 4 high-quality studies. Seven of 22 studies demonstrated a significant decrease in blood pressure, but only one was of high quality. Two of four high-quality studies pointed towards effects on total cholesterol while other lipidemic parameters were not affected., Conclusions: No compelling data exist that grape polyphenols can positively influence glycemia, blood pressure or lipid levels in individuals with or without the metabolic syndrome. Limited evidence suggests that grape polyphenols may improve insulin sensitivity.