Purpose
Benzodiazepines are effective medicines for insomnia and anxiety but are commonly used beyond recommended treatment time frames, which may lead to adverse drug events. The aim of this ...systematic review was to critically evaluate the success of interventions used to reduce benzodiazepines and ‘Z-drug’ use, and the impact of these interventions on clinical outcomes in older adults.
Methods
A search was conducted in PubMed, Embase, Informit, International Pharmaceutical Abstracts, Scopus, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL. Studies conducted in older adults (≥65 years) and published between January 1995 and July 2015 were included. Two authors independently reviewed all articles for eligibility and extracted the data.
Results
Seven studies of benzodiazepines and Z-drug withdrawal were identified. Benzodiazepine discontinuation rates were 64.3% in one study that employed pharmacological substitution with melatonin and 65.0% in a study that employed general practitioner-targeted intervention. Mixed interventions including patient education and tapering (
n
= 2), pharmacological substitution with psychological support (
n
= 1) and tapering with psychological support (
n
= 1) yielded discontinuation rates between 27.0 and 80.0%. Five studies measured clinical outcomes following benzodiazepine discontinuation. Most (
n
= 4) observed no difference in prevalence of withdrawal symptoms or sleep quality, while one study reported decline in quality of life in those who continued taking benzodiazepine vs. those who discontinued over 8 months.
Conclusions
Current evidence shows that benzodiazepine withdrawal is feasible in the older population, but withdrawal rates vary according to the type of intervention. As the benefits and sustainability of these interventions are unclear, further studies should be conducted to assess this.
There are no effective treatments available to halt or reverse the progression of age-related cognitive decline and Alzheimer's disease. Thus, there is an urgent need to understand the underlying ...mechanisms of disease etiology and progression to identify novel therapeutic targets. Age-related changes to the vasculature, particularly increases in stiffness of the large elastic arteries, are now recognized as important contributors to brain aging. There is a growing body of evidence for an association between greater large artery stiffness and cognitive impairment among both healthy older adults and patients with Alzheimer's disease. However, studies in humans are limited to only correlative evidence, whereas animal models allow researchers to explore the causative mechanisms linking arterial stiffness to neurocognitive dysfunction and disease. Recently, several rodent models of direct modulation of large artery stiffness and the consequent effects on the brain have been reported. Common outcomes among these models have emerged, including evidence that greater large artery stiffness causes cerebrovascular dysfunction associated with increased oxidative stress and inflammatory signaling. The purpose of this mini-review is to highlight the recent findings associating large artery stiffness with deleterious brain outcomes, with a specific focus on causative evidence obtained from animal models. We will also discuss the gaps in knowledge that remain in our understanding of how large artery stiffness affects brain function and disease outcomes.
Background
Inappropriate medication use is common in the elderly and the risks associated with their use are well known. The term deprescribing has been utilised to describe the complex process that ...is required for the safe and effective cessation of inappropriate medications. Given the primacy of the consumer in health care, their views must be central in the development of any deprescribing process.
Objectives
The aim of this study was to identify barriers and enablers that may influence a patient’s decision to cease a medication.
Data sources
A systematic search of MEDLINE, International Pharmaceutical Abstracts, EMBASE, CINAHL, Informit and Scopus was conducted and augmented with a manual search. Numerous search terms relating to withdrawal of medications and consumers’ beliefs were utilised.
Study eligibility criteria
Articles were included if the barriers or enablers were directly patient/carer reported and related to long-term medication(s) that they were currently taking or had recently ceased.
Study appraisal and synthesis methods
Determination of relevance and data extraction was performed independently by two reviewers. Content analysis with coding was utilised for synthesis of results.
Results
Twenty-one articles met the criteria and were included in the review. Three themes, disagreement/agreement with ‘appropriateness’ of cessation, absence/presence of a ‘process’ for cessation, and negative/positive ‘influences’ to cease medication, were identified as both potential barriers and enablers, with ‘fear’ of cessation and ‘dislike’ of medications as a fourth barrier and enabler, respectively. The most common barrier/enabler identified was ‘appropriateness’ of cessation, with 15 studies identifying this as a barrier and 18 as an enabler.
Conclusions and implications of key findings
The decision to stop a medication by an individual is influenced by multiple competing barriers and enablers. Knowledge of these will aid in the development of a deprescribing process, particularly in approaching the topic of cessation with the patient and what process should be utilised. However, further research is required to determine if the proposed patient-centred deprescribing process will result in improved patient outcomes.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Objectives
To capture people's attitudes, beliefs, and experiences regarding the number of medications they are taking and their feelings about stopping medications.
Design
Administration of a ...validated questionnaire.
Setting
Multidisciplinary ambulatory consulting service at the Royal Adelaide Hospital.
Participants
Participants were individuals aged 18 and older (median 71.5) taking at least one regular prescription medication; 100 participants completed all items of the questionnaire, 65 of whom were aged 65 and older.
Measurements
Participants were administered the 15‐item Patients' Attitudes Towards Deprescribing (PATD) questionnaire.
Results
Participants were taking an average of 10 different prescription and nonprescription (including complementary), regular and as‐needed medications. More than 60% felt that they were taking a “large number” of medications, and 92% stated that they would be willing to stop one or more of their current medications if possible. Number of regular medications, age, and number of medical conditions were not found to be correlated with willingness to stop a medication. The findings were similar in older and younger participants.
Conclusion
This study has shown that a cohort of mostly older adults were largely accepting of a trial of cessation of medication(s) that their prescriber deemed to be no longer required. Because few factors were associated with willingness to cease medications, all patients should be individually evaluated for deprescribing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular ...impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically
and
genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.
Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine ...blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response.
To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention.
SBP and DBP and BP surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings.
Twenty five firefighters (43.4 ± 13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ± 12.9 to 10.5 ± 11.7 mmHg, P < 0.05; DBP surge from 8.2 ± 10.8 to 4.9 ± 5.6 mmHg, P > 0.05) after intervention. We confirm that clinical (127.6 ± 9.1 to 120 ± 8.2 mmHg) and central (122.7 ± 11.3 to 118.2 ± 10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ± 1.5 to 11.2 ± 2.2 U/ml) and nitric oxide (40.4 ± 7 to 48.9 ± 16.9 μmol/l) levels improve with an exercise and diet intervention.
These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders.
One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age ...modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent dilation was similar between the static and low pulse pressure conditions. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young mice, mediated by less nitric oxide bioavailability and greater oxidative stress. Cerebral arteries from old mice had impaired cerebral artery endothelium-dependent dilation at static pressure compared with young cerebral arteries. However, exposure to low or high pulse pressure did not cause any further impairments to endothelium-dependent dilation in old cerebral arteries compared with static pressure. The old cerebral arteries had less distension during exposure to high pulse pressure and greater stiffness compared with young cerebral arteries. These results indicate that acute exposure to high pulse pressure impairs endothelium-dependent dilation in young, but not old, cerebral arteries. The greater stiffness of cerebral arteries from old mice potentially protects against the negative consequences of high pulse pressure.
•High pulse pressure impairs cerebral artery endothelial function in young mice.•Old cerebral arteries are protected against damage by high pulse pressure.•Old cerebral arteries are stiffer and distend less at high pulse pressure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Multimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to ...assess patients' attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe.
We analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness.
Data from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81).
The willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients' awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Deprescribing is a holistic process of medication cessation that encompasses gaining a comprehensive medication list, identifying potentially inappropriate medications, deciding if the identified ...medication can be ceased, planning the withdrawal regimen and monitoring, support and follow-up. It is currently being investigated as a mechanism to reduce unnecessary or redundant medications. However, given the systematic and patient-centred nature of the deprescribing process, it is possible that it may also confer additional benefits such as improving adherence to medications, even if there is no net reduction in overall medication use. Specifically, deprescribing may improve adherence via reducing polypharmacy, reducing the financial costs associated with medication taking, increasing the patient’s medication knowledge through education, increasing patient engagement in medication management and resolution of adverse drug reactions. More research into deprescribing must be conducted to establish if these potential benefits can be realised, in addition to establishing any negative consequences.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for ...deprescribing interventions in older adults. 11 databases were searched from 1.sup.st January 2005 to 16.sup.th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. PROSPERO CRD42020178860.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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