Introduction There are robust associations between use of anticholinergic medicines and adverse effects in older people. However, the nature of these associations for older people living with frailty is yet to be established. Objectives The aims were to identify and investigate associations between anticholinergics and adverse outcomes in older people living with frailty and to investigate whether exposure is associated with greater risks according to frailty status. Methods MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and PsycINFO were searched to 1 August 2019. Observational studies reporting associations between anticholinergics and outcomes in older adults (average age ≥ 65 years) that reported frailty using validated measures were included. Primary outcomes were physical impairment, cognitive dysfunction, and change in frailty status. Risk of bias was evaluated using the Cochrane Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken where appropriate. Results Thirteen studies (21,516 participants) were included (ten community, one residential aged-care facility and two hospital studies). Observed associations included reduced ability for chair standing, slower gait speeds, poorer physical performance, increased risk of falls and mortality. Conflicting results were reported for grip strength, timed up and go test, cognition and activities of daily living. No associations were observed for transitions between frailty states, psychological wellbeing or benzodiazepine-related adverse reactions. There was no clear evidence of differences in risks according to frailty status. Conclusions Anticholinergics are associated with adverse outcomes in older people living with frailty; however, the literature has significant methodological limitations. There is insufficient evidence to suggest greater risks based on frailty, and there is an urgent need to evaluate this further in well-designed studies stratifying by frailty.

BackgroundStatins reduce the risk of major adverse cardiovascular events (MACE), however, their clinical benefit for primary and secondary prevention among older adults with frailty is uncertain. This review investigates whether statins prescribed for primary and secondary prevention are associated with reduced MACE among adults aged ≥65 years with frailty. MethodsSystematic review of studies published between 01.01.1952 and 01.01.2019 in MEDLINE, Embase, Scopus, Web of Science, Cochrane Library and the International Pharmaceutical Abstracts. Studies that investigated the effect of statins on MACE among adults ≥65 years with a validated frailty assessment were included. Data were extracted from the papers as per a pre-published protocol, PROSPERO: CRD42019127486. Risk of bias was assessed using the Cochrane Risk of Bias in non-randomised studies of interventions. FindingSix cohort studies fulfilled the inclusion criteria. There were no randomised clinical trials. Of studies involving statins for primary and secondary prevention (n=6), one found statins were associated with reduced mortality (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.37-0.93) and another found they were not (p=0.73). One study of statins used for secondary prevention found they were associated with reduced mortality (HR 0.28, 95%CI 0.21-0.39).No studies investigated the effect of statins for primary prevention or the effect of statins on the frequency of MACE. DiscussionThis review identified only observational evidence that, among older people with frailty, statins are associated with reduced mortality when prescribed for secondary prevention, and an absence of evidence evaluating statin therapy for primary prevention. Randomised trial data are needed to better inform the use of statins among older adults living with frailty.

Introduction Medications with Anticholinergic (AC) properties, are prescribed to treat a range of conditions. Older people are increasingly likely to be prescribed multiple AC medications, but are also more likely to experience unwanted adverse effects, such as falls and delirium. The risks of adverse outcomes increase with the number and potency of AC medications prescribed. The aim of this study was to use a prognostic modelling approach to develop an AC Medication Index (ACMI) that identifies patients at high risk of AC medication side effects. Methods The prognostic model was developed using data on patients aged 65–95 years, registered with a general practice contributing data to ‘Connected Bradford’ in 2019. A Time-dependent Cox model was fitted, with hospital admission for delirium or falls as the composite outcome and AC medications, age, sex and important clinical factors (e.g. dementia, arthritis, urinary incontinence) as predictors. Concordance and Negalkerke’s R2 derived from five-fold cross-validation were used to assess model performance. Results There were 151,604 patients included in the study, of whom 47,035 (31.0%) were prescribed ≥1 AC medication during 2019. Codeine, Prednisolone, Furosemide and Amitriptyline were most commonly prescribed with 7.4%, 4.0%, 3.8% and 3.1% of patients prescribed these medications at least once in 2019, respectively. During 2019, 6,078 (4.0%) patients experienced a hospital admission with delirium or a fall, with the rate being increased in those prescribed ≥1 AC medication during 2019 (4.8% vs 3.7%; p < 0.001). The prognostic model yielded a discrimination statistic of 0.86 with an R2 of 0.1. Conclusion The model used to develop the ACMI shows good discrimination. External validation will soon be performed using data from the SAIL databank and the ACMI will be further developed as a tool for use in primary care.

Anticholinergic medicines are routinely prescribed to manage a variety of clinical conditions, but are potentially inappropriate in the treatment of older people, especially those living with frailty. Here, the authors describe how their AC‐FRAIL tool can assist practices to identify frail older people within a practice population who are at greatest risk from anticholinergic burden.