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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 In the event of intolerance or side effects, medication should be switched or withdrawn.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. [ABSTRACT FROM AUTHOR]

Abstract Background The Bramwell-Hill model describes the relation between vascular wall stiffness expressed in aortic distensibility and the pulse wave velocity (PWV), which is the propagation speed of the systolic pressure wave through the aorta. The main objective of this study was to test the validity of this model locally in the aorta by using PWV-assessments based on in-plane velocity-encoded cardiovascular magnetic resonance (CMR), with invasive pressure measurements serving as the gold standard. Methods Seventeen patients (14 male, 3 female, mean age ± standard deviation = 57 ± 9 years) awaiting cardiac catheterization were prospectively included. During catheterization, intra-arterial pressure measurements were obtained in the aorta at multiple locations 5.8 cm apart. PWV was determined regionally over the aortic arch and locally in the proximal descending aorta. Subsequently, patients underwent a CMR examination to measure aortic PWV and aortic distention. Distensibility was determined locally from the aortic distension at the proximal descending aorta and the pulse pressure measured invasively during catheterization and non-invasively from brachial cuff-assessment. PWV was determined regionally in the aortic arch using through-plane and in-plane velocity-encoded CMR, and locally at the proximal descending aorta using in-plane velocity-encoded CMR. Validity of the Bramwell-Hill model was tested by evaluating associations between distensibility and PWV. Also, theoretical PWV was calculated from distensibility measurements and compared with pressure-assessed PWV. Results In-plane velocity-encoded CMR provides stronger correlation (p = 0.02) between CMR and pressure-assessed PWV than through-plane velocity-encoded CMR (r = 0.69 versus r = 0.26), with a non-significant mean error of 0.2 ± 1.6 m/s for in-plane versus a significant (p = 0.006) error of 1.3 ± 1.7 m/s for through-plane velocity-encoded CMR. The Bramwell-Hill model shows a significantly (p = 0.01) stronger association between distensibility and PWV for local assessment (r = 0.8) than for regional assessment (r = 0.7), both for CMR and for pressure-assessed PWV. Theoretical PWV is strongly correlated (r = 0.8) with pressure-assessed PWV, with a statistically significant (p = 0.04) mean underestimation of 0.6 ± 1.1 m/s. This theoretical PWV-estimation is more accurate when invasively-assessed pulse pressure is used instead of brachial cuff-assessment (p = 0.03). Conclusions CMR with in-plane velocity-encoding is the optimal approach for studying Bramwell-Hill associations between local PWV and aortic distensibility. This approach enables non-invasive estimation of local pulse pressure and distensibility.

Human in vivo models of systemic inflammation are used to study the physiological mechanisms of inflammation and the effect of drugs and nutrition on the immune response. Although in vivo lipopolysaccharide (LPS) challenges have been applied as methodological tool in clinical pharmacology studies, detailed information is desired on dose-response relationships, especially regarding LPS hyporesponsiveness observed after low-dose in vivo LPS administration. A study was performed to assess the in vivo inflammatory effects of low intravenous LPS doses, and to explore the duration of the induced LPS hyporesponsiveness assessed by subsequent ex vivo LPS challenges. This was a randomized, double-blind, placebo-controlled study with single ascending low doses of LPS (0.5, 1 and 2 ng/kg body weight) administered to healthy male volunteers (3 cohorts of 8 subjects, LPS:placebo 6:2). The in vivo inflammatory response was assessed by measurement of cytokines and CRP. Ex vivo LPS challenges were performed (at -2, 6, 12, 24, 48 and 72 hours relative to in vivo LPS administration) to estimate the duration and magnitude of LPS hyporesponsiveness by assessment of cytokine release (TNF-α, IL-1β, IL- 6, IL-8). LPS administration dose-dependently increased body temperature (+1.5 °C for 2 ng/kg LPS), heart rate (+28 bpm for 2 ng/kg LPS), CRP and circulating cytokines which showed clearly distinctive increases from placebo already at the lowest LPS dose level tested (0.5 ng/kg, contrast for timeframe 0-6 hours: TNF-α +413%, IL-6 +288%, IL-8 +254%; all p ⩽ 0.0001). In vivo LPS administration dose-dependently induced a period of hyporesponsiveness in the ex vivo LPS-induced cytokine release (IL-1β, IL-6 and TNF-α), with maximal hyporesponsiveness observed at 6 hours, lasting no longer than 12 hours. For IL-6 and IL-8, indications for immune cell priming were observed. We demonstrated that an in vivo LPS challenge, with LPS doses as low as 0.5 ng/kg, elicits a cytokine response that is clearly distinctive from baseline cytokine levels. This study expanded the knowledge about the dose-effect relationship of LPS-induced hyporesponsiveness. As such, the low-dose LPS challenge has been demonstrated to be a feasible methodological tool for future clinical studies exploring pharmacological or nutritional immune-modulating effects. [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.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have gained prominence in the treatment of diabetes mellitus type 2, heart failure, and chronic kidney disease. However, concerns arise for frail older adults, given their underrepresentation in trials and heightened susceptibility to adverse drug events. This review summarizes the clinical effects of SGLT2 inhibitors in older adults with frailty. SGLT2 inhibitors seem to exhibit consistent cardiovascular benefits irrespective of age. As such, these drugs can be beneficial for older adults with 'cardiovascular frailty': in other words, cardiovascular multimorbidity. However, in the current data there is a lack of focus on the broader definition of frailty, which also includes functional status and self-dependence. Also, some research suggest that adverse events, such as volume depletion and genitourinary infections, are more common in the frail older population. Therefore, until more data is available, SGLT2 inhibitors should be prescribed with caution in older adults living with frailty.

Background: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention., Design: systematic review and meta-analysis., Data Sources: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022., Eligibility Criteria: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome., Study Records: title/abstract and full-text screening by two reviewers., Risk of Bias: Cochrane Collaboration revised tool., Data Synthesis: results reported separately for different settings and sufficiently comparable studies meta-analysed., Results: forty-nine heterogeneous studies were included., Community: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85-1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70-1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69-1.14, I2 = 0%, 2 s) for injurious falls., Hospital: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74-1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07-3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively., Long-Term Care: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72-1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64-1.35, I2 = 92%, 7 s) for number of falls., Conclusions: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls.PROSPERO registration number: CRD42020218231., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Cardiovascular disorders are increasingly recognised as important fall risk factors in older adults. Falls are a major public health problem in older adults, and therefore, effective interventions for reducing falls are essential for this population. Cardiovascular disease is a clinically relevant (but often overlooked) and potentially modifiable risk factor for falls. Literature describing the effects of cardiovascular assessments and treatments on fall prevention has generally focused on only one specific test or treatment. A comprehensive, comparative overview surrounding the effectiveness of available assessments and treatments on cardiovascular related fall risk is currently lacking., Methods and Analysis: A scoping review and evidence map will be conducted to summarise the available evidence regarding the (comparative) effectiveness of cardiovascular assessments and therapeutic interventions on reducing fall risk in older individuals. A systematic and comprehensive literature search will be performed in MEDLINE and Embase using the key components 'older adults', 'cardiovascular evaluation', 'cardiovascular intervention' and 'falls'. Furthermore, we will create an evidence map to summarise the quantity and quality of currently available evidence identified in the scoping review. The evidence map will consider, but will not be limited to, observational studies, randomised controlled trials and reviews evaluating cardiovascular tests and treatments (vs controls) on fall risk in older adults., Ethics and Dissemination: The scoping review and evidence map will only include data that are publicly available and, therefore, ethical approval is not required. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Case Description: A frail 85-year-old woman with chronic neuropathic pain after hip surgery, not responding to treatment with acetaminophen and morphine patches. Should she be prescribed a gabapentinoid?, Discussion: Gabapentinoids and antidepressants are considered first-line therapies. They achieve clinically relevant (i.e. ≥ 50%) pain reduction in approximately one-third of patients with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is limited. Adverse events occur frequently and are mostly mild in nature; serious adverse effects are rare. Prescription of gabapentinoids in specific patient groups (e.g. elderly patients and patients with a history of depression or substance abuse) deserves careful consideration, because the risk/benefit ratio in those groups may be altered. In order to reduce the risk of withdrawal symptoms, slow tapering is recommended., Conclusion: Chronic neuropathic pain often has a negative impact on the quality of life and is difficult to treat. In general, treatment with a gabapentinoid is a possible first-line treatment option. However, they may be relatively contraindicated in vulnerable patients.