Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.

INTRODUCTION: Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls. METHODS: We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults. RESULTS: We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461). DISCUSSION: Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.

The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.

BACKGROUND: Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status. METHODS: Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum). RESULTS: In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)). CONCLUSIONS: Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.

New Horizons in the use of routine data for ageing research.

The past three decades have seen a steady increase in the availability of routinely collected health and social care data and the processing power to analyse it. These developments represent a major opportunity for ageing research, especially with the integration of different datasets across traditional boundaries of health and social care, for prognostic research and novel evaluations of interventions with representative populations of older people. However, there are considerable challenges in using routine data at the level of coding, data analysis and in the application of findings to everyday care. New Horizons in applying routine data to investigate novel questions in ageing research require a collaborative approach between clinicians, data scientists, biostatisticians, epidemiologists and trial methodologists. This requires building capacity for the next generation of research leaders in this important area. There is a need to develop consensus code lists and standardised, validated algorithms for common conditions and outcomes that are relevant for older people to maximise the potential of routine data research in this group. Lastly, we must help drive the application of routine data to improve the care of older people, through the development of novel methods for evaluation of interventions using routine data infrastructure. We believe that harnessing routine data can help address knowledge gaps for older people living with multiple conditions and frailty, and design interventions and pathways of care to address the complex health issues we face in caring for older people.

Is the association between blood pressure and mortality in older adults different with frailty? A systematic review and meta-analysis.

OBJECTIVE: to investigate whether the association between blood pressure and clinical outcomes is different in older adults with and without frailty, using observational studies. METHODS: MEDLINE, EMBASE and CINAHL were searched from 1st January 2000 to 13th June 2018. PROSPERO CRD42017081635. We included all observational studies reporting clinical outcomes in older adults with an average age over 65 years living in the community with and without treatment that measured blood pressure and frailty using validated methods. Two independent reviewers evaluated study quality and risk of bias using the ROBANS tool. We used generic inverse variance modelling to pool risks of all-cause mortality adjusted for age and sex. RESULTS: nine observational studies involving 21,906 older adults were included, comparing all-cause mortality over a mean of six years. Fixed effects meta-analysis of six studies demonstrated that in people with frailty, there was no mortality difference associated with systolic blood pressure <140 mm Hg compared to systolic blood pressure >140 mm Hg (HR 1.02, 95% CI 0.90 to 1.16). In the absence of frailty, systolic blood pressure <140 mm Hg was associated with lower risk of death compared to systolic blood pressure >140 mm Hg (HR 0.86, 95% CI 0.77 to 0.96). CONCLUSIONS: evidence from observational studies demonstrates no mortality difference for older people with frailty whose systolic blood pressure is <140 mm Hg, compared to those with a systolic blood pressure >140 mm Hg. Current evidence fails to capture the complexities of blood pressure measurement, and the association with non-fatal outcomes.

A systematic review of the evidence that brain structure is related to muscle structure and their relationship to brain and muscle function in humans over the lifecourse.

BACKGROUND: An association between cognition and physical function has been shown to exist but the roles of muscle and brain structure in this relationship are not fully understood. A greater understanding of these relationships may lead to identification of the underlying mechanisms in this important area of research. This systematic review examines the evidence for whether: a) brain structure is related to muscle structure; b) brain structure is related to muscle function; and c) brain function is related to muscle structure in healthy children and adults. METHODS: Medline, Embase, CINAHL and PsycINFO were searched on March 6th 2014. A grey literature search was performed using Google and Google Scholar. Hand searching through citations and references of relevant articles was also undertaken. RESULTS: 53 articles were included in the review; mean age of the subjects ranged from 8.8 to 85.5 years old. There is evidence of a positive association between both whole brain volume and white matter (WM) volume and muscle size. Total grey matter (GM) volume was not associated with muscle size but some areas of regional GM volume were associated with muscle size (right temporal pole and bilateral ventromedial prefrontal cortex). No evidence was found of a relationship between grip strength and whole brain volume however there was some evidence of a positive association with WM volume. Conversely, there is evidence that gait speed is positively associated with whole brain volume; this relationship may be driven by total WM volume or regional GM volumes, specifically the hippocampus. Markers of brain ageing, that is brain atrophy and greater accumulation of white matter hyperintensities (WMH), were associated with grip strength and gait speed. The location of WMH is important for gait speed; periventricular hyperintensities and brainstem WMH are associated with gait speed but subcortical WMH play less of a role. Cognitive function does not appear to be associated with muscle size. CONCLUSION: There is evidence that brain structure is associated with muscle structure and function. Future studies need to follow these interactions longitudinally to understand potential causal relationships.

Frailty and cerebrovascular disease: Concepts and clinical implications for stroke medicine.

Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings.

Systolic blood pressure and outcomes in frail older adults.

Hypertension is diagnosed in the majority of older people with frailty, in whom blood pressure prognosis is not well understood. This editorial describes recent evidence on blood pressure and outcomes in older people with frailty.

Disseminated bacillus Calmette-Guérin (BCG): a cause of delirium in an older adult.

Intra-vesical Bacillus Calmette-Guérin (BCG) immunotherapy is an effective treatment for high-risk bladder cancer. Less well known is that fewer than 1% of patients receiving BCG treatment can develop disseminated BCG. The reaction can range from a mild flu-like illness to a systemic disorder with a fulminant course which in the most severe cases can lead to death. The diagnostic yield is low and diagnosis is often made after a comprehensive exclusion of more common causes of pyrexia of unknown origin. A high level of suspicion is therefore required in those who may be at risk. We report a case of disseminated BCG in an older patient for whom early involvement of his family was pertinent to determining the precipitant for delirium.

Delirium: a guide for the general physician.

Delirium describes a sudden onset change in mental status of fluctuating course. This is a state of altered consciousness characterised chiefly by inattention or lack of arousal, but can also include new impairment of language, perception and behaviour. Certain predisposing factors can make an individual more susceptible to delirium in the face of a stressor. Stressors include direct insults to the brain, insults peripheral to the brain or external changes in the environment of an individual. Delirium is varied in its presentation, and can be categorised by the psychomotor profile as: hyperactive type (overly vigilant, agitated, often wandersome), hypoactive type (sedate or withdrawn) or mixed types.

Sleep Disruption at Home As an Independent Risk Factor for Postoperative Delirium.

OBJECTIVES: To determine whether sleep disruption at home or in hospital is an independent risk factor for postoperative delirium in older adults undergoing elective surgery. DESIGN: Prospective cohort study. SETTING: German teaching hospital. PARTICIPANTS: Individuals aged 65 and older undergoing elective arthroplasty (N = 101). MEASUREMENTS: Preoperative questionnaires were used to assess sleep disruption at home (Pittsburgh Sleep Quality Index). Actigraphy was used to objectively measure sleep disruption in the hospital before and after surgery. Delirium was assessed daily after surgery using the Confusion Assessment Method and, if there was uncertainty, validated according to International Classification of Diseases, Tenth Revision (ICD-10), criteria. RESULTS: Twenty-seven participants developed postoperative delirium. Those with sleep disruption at home were 3.26 times as likely to develop postoperative delirium as those without (95% confidence interval (CI) = 1.34-7.92, P = .009). Participants with sleep disruption in hospital were 1.21 times as likely to develop postoperative delirium as those without (95% CI = 1.03-1.41, P = .02). When adjusting for other variables, risk remained significant for sleep disruption at home (risk ratio (RR) = 3.90, 95% CI = 2.14-7.11, P < .001) but not in the hospital (RR = 1.19, 95% CI = 0.69-2.07). Jointly modeling sleep disruption at home and in the hospital, adjusted for covariates, resulted in significant contributions of both (home: RR = 3.10, 95% CI = 1.34-7.17, P = .008; hospital: RR = 1.38 95% CI = 1.13-1.68, P = .002). CONCLUSIONS: Older people with sleep disruption at home are at significantly higher risk of developing postoperative delirium than those without. Sleep disruption in the hospital may further heighten this risk.

Delirium: a guide for the general physician.

Delirium describes a sudden onset change in mental status of fluctuating course. This is a state of altered consciousness characterised chiefly by inattention or lack of arousal, but can also include new impairment of language, perception and behaviour. Certain predisposing factors can make an individual more susceptible to delirium in the face of a stressor. Stressors include direct insults to the brain, insults peripheral to the brain or external changes in the environment of an individual. Delirium is varied in its presentation, and can be categorised by the psychomotor profile as: hyperactive type (overly vigilant, agitated, often wandersome), hypoactive type (sedate or withdrawn) or mixed types.