Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. METHODS:   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, I(2) = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I(2) = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I(2) = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I(2) = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I(2) = 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, I(2) = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I(2) = 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: CRD4202021823

Bramwell-Hill modeling for local aortic pulse wave velocity estimation: a validation study with velocity-encoded cardiovascular magnetic resonance and invasive pressure assessment

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>Conclusions</p> <p>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.</p

Opioids and Falls Risk in Older Adults: A Narrative Review

Pain treatment is important in older adults but may result in adverse events such as falls. Opioids are effective for nociceptive pain but the evidence for neuropathic pain is weak. Nevertheless, both pain and opioids may increase the risk of falls. This narrative literature review aims to summarize the existing knowledge on the opioid-related fall risk in older adults, including the pharmacokinetics and pharmacodynamics, and assist clinicians in prescribing and deprescribing opioids in older persons. We systematically searched relevant literature on opioid-related fall risk in older adults in PubMed and Scopus in December 2020. We reviewed the literature and evaluated fall-related adverse effects of opioids, explaining how to optimally approach deprescribing of opioids in older adults. Opioid use increases fall risk through drowsiness, (orthostatic) hypotension and also through hyponatremia caused by weak opioids. When prescribing, opioids should be started with low dosages if possible, keeping in mind their metabolic genetic variation. Falls are clinically significant adverse effects of all opioids, and the risk may be dose dependent and highest with strong opioids. The risk is most prominent in older adults prone to falls. To reduce the risk of falls, both pain and the need for opioids should be assessed on a regular basis, and deprescribing or changing to a lower dosage or safer alternative should be considered if the clinical condition allows. Deprescribing should be done by reducing the dosage gradually and by assessing and monitoring the pain and withdrawal symptoms at the same time. Weighing the risks and benefits is necessary before prescribing opioids, especially to older persons at high risk of falls. Clinical decision tools assist prescribers in clinical decisions regarding (de-) prescribing

Wel of geen gabapentinoïden bij volwassenen met chronische neuropathische pijn?

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

Impact of cardiovascular evaluations and interventions on fall risk in older adults: a protocol for a scoping review and evidence map

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

Characterization of inflammation and immune cell modulation induced by low-dose LPS administration to healthy volunteers

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-alpha, IL-1 beta, IL-6, IL-8). LPS administration dose-dependently increased body temperature (+1.5 degrees 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-alpha+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-1 beta, IL-6 and TNF-alpha), 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 effect

Wel of geen gabapentinoïden bij volwassenen met chronische neuropathische pijn?

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