Prescribing of direct oral anticoagulants and warfarin to older people with atrial fibrillation in UK general practice: a cohort study.

BACKGROUND: Anticoagulation for stroke prevention in atrial fibrillation (AF) has, historically, been under-used in older people. The aim of this study was to investigate prescribing of oral anticoagulants (OACs) for people aged ≥ 75 years in the UK before and after direct oral anticoagulants (DOACs) became available. METHODS: A cohort of patients aged ≥ 75 years with a diagnosis of AF was derived from the Clinical Practice Research Datalink (CPRD) between January 1, 2003, and December 27, 2017. Patients were grouped as no OAC, incident OAC (OAC newly prescribed) or prevalent OAC (entered study on OAC). Incidence and point prevalence of OAC prescribing were calculated yearly. The risk of being prescribed an OAC if a co-morbidity was present was calculated; the risk difference (RD) was reported. Kaplan-Meier curves were used to explore persistence with anticoagulation. A Cox regression was used to model persistence with warfarin and DOACs over time. RESULTS: The cohort comprised 165,596 patients (66,859 no OAC; 47,916 incident OAC; 50,821 prevalent OAC). Incidence of OAC prescribing increased from 111 per 1000 person-years in 2003 to 587 per 1000 person-years in 2017. Older patients (≥ 90 years) were 40% less likely to receive an OAC (RD -0.40, 95% CI -0.41 to -0.39) than younger individuals (75-84 years). The likelihood of being prescribed an OAC was lower with a history of dementia (RD -0.34, 95% CI -0.35 to -0.33), falls (RD -0.17, 95% CI -0.18 to -0.16), major bleeds (RD -0.17, 95% CI -0.19 to -0.15) and fractures (RD -0.13, 95% CI -0.14 to -0.12). Persistence with warfarin was higher than DOACs in the first year (0-1 year: HR 1.25, 95% CI 1.17-1.33), but this trend reversed by the third year of therapy (HR 0.75, 95% CI 0.63-0.89). CONCLUSIONS: OAC prescribing for older people with AF has increased; however, substantial disparities persist with age and co-morbidities. Whilst OACs should not be withheld solely due to the risk of falls, these results do not reflect this national guidance. Furthermore, the under-prescribing of OACs for patients with dementia or advancing age may be due to decisions around risk-benefit management. TRIAL REGISTRATION: EUPAS29923 . First registered on: 27/06/2019.

Estimating premorbid intelligence in people living with dementia: a systematic review.

OBJECTIVES: In diagnosing dementia, estimating premorbid functioning is critical for accurate detection of the presence and severity of cognitive decline. However, which assessments of premorbid intelligence are most suitable for use in clinical practice is not well established. Here, we systematically evaluate the validity of instruments for measuring premorbid intelligence in people living with dementia. DESIGN AND SETTING: In this systematic review, electronic databases (EMBASE, PsycINFO, MEDLINE, CINAHL, and AMED) were searched to identify studies reporting on objective measures of premorbid intelligence in dementia. Participants from included studies were recruited from local communities and clinical settings. PARTICIPANTS: A total of 1082 patients with dementia and 2587 healthy controls were included in the review. MEASUREMENTS: The literature search resulted in 13 eligible studies describing 19 different instruments. The majority of instruments (n = 14) consisted of language-based measures, with versions of the National Adult Reading Test (NART) being most commonly investigated. RESULTS: Preliminary evidence suggested comparable performance of patients with mild dementia and healthy controls on word reading tasks in English, Portuguese, Swedish, and Japanese. In moderate dementia, however, the performance was significantly impaired on most verbal tasks. There was a lack of reliability and validity testing of available instruments, with only one of the included studies reporting psychometric properties within the patient group. CONCLUSIONS: The results demonstrate that there is a wide range of tools available for estimating premorbid intelligence in dementia, with cautious support for the potential of word reading tasks across different languages in individuals with mild dementia. However, the review highlights the urgent need for extensive assessments of the psychometric properties of these tasks in dementia. We propose that further longitudinal research and assessments of nonverbal measures are necessary to validate these instruments and enhance diagnostic procedures for people living with dementia worldwide.

COVID-19 in older people: a rapid clinical review.

INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.

The treatment of hypertension in people with dementia: a systematic review of observational studies.

BACKGROUND: Hypertension is very common in older people and a number of trials of antihypertensives have demonstrated benefit from treatment in even the oldest old. However, people with dementia were significantly under-represented in these studies and as a population are more likely to be physically frail, to suffer orthostatic hypotension and to experience adverse effects from polypharmacy at a lower drug count. It may be that different thresholds for commencement and cessation of treatment should be considered and may already be used for this group. Against this background this review sets out to describe the prevalence of hypertension in people with dementia, its treatment, change in treatment over time and the achievement of blood pressure (BP) control. METHODS: The PubMed, Cochrane, Embase and PsychINFO databases were searched for observational studies involving people with dementia and a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onwards. Abstracts and titles were then reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analysed and appraised. RESULTS: Thirteen articles were identified for analysis. The prevalence of hypertension in people with dementia was 45% (range 35%-84%). 73% of these were on at least one antihypertensive, with diuretics being the most common. The reported prevalence of hypertension in study populations remained unchanged over time. ACEi/ARBs and calcium channel blockers were prescribed more frequently in more recent studies whilst use of ß-blockers and diuretics remained unchanged. Target blood pressure was achieved in 55% of those on treatment. CONCLUSION: Hypertension is as common in people with dementia as in other populations and is as commonly treated with antihypertensive drugs. The findings presented here will support further work to establish the risk-benefit of antihypertensive treatment in patients with dementia and, if differing ratios are identified, to establish dementia-specific guidelines for management.

A pragmatic cluster randomised controlled trial of air filtration to prevent symptomatic winter respiratory infections (including COVID-19) in care homes (AFRI-c) in England: Trial protocol.

BACKGROUND: Respiratory tract infections are readily transmitted in care homes. Airborne transmission of pathogens causing respiratory tract illness is largely unmitigated. Portable high-efficiency-particulate-air (HEPA) filtration units capture microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. The Air Filtration to prevent symptomatic winter Respiratory Infections (including COVID-19) in care homes (AFRI-c) randomized controlled trial will determine whether using HEPA filtration units reduces respiratory infection episodes in care home residents. METHODS: AFRI-c is a cluster randomized controlled trial that will be delivered in residential care homes for older people in England. Ninety-one care homes will be randomised to take part for one winter period. The intervention care homes will receive HEPA filtration units for use in communal areas and private bedrooms. Normal infection control measures will continue in all care homes. Anonymised daily data on symptoms will be collected for up to 30 residents. Ten to 12 of these residents will be invited to consent to a primary care medical notes review and (in intervention homes) to having an air filter switched on in their private room. The primary outcome will be number of symptomatic winter respiratory infection episodes. Secondary outcomes include specific clinical measures of infection, number of falls / near falls, number of laboratory confirmed infections, hospitalisations, staff sickness and cost-effectiveness. A mixed methods process evaluation will assess intervention acceptability and implementation. DISCUSSION: The results of AFRI-c will provide vital information about whether portable HEPA filtration units reduce symptomatic winter respiratory infections in older care home residents. Findings about effectiveness, fidelity, acceptability and cost-effectiveness will support stakeholders to determine the use of HEPA filtration units as part of infection control policies.

Anticoagulant use in older persons at risk for falls: therapeutic dilemmas-a clinical review.

PURPOSE: The aim of this clinical narrative review was to summarise the existing knowledge on the use of anticoagulants and potential adverse events in older people at risk of falls with a history of atrial fibrillation or venous thromboembolism. The review also offers practical steps prescribers can take when (de-)prescribing anticoagulants to maximise safety. METHODS: Literature searches were conducted using PubMed, Embase and Scopus. Additional articles were identified by searching reference lists. RESULTS: Anticoagulants are often underused in older people due to concerns about the risk of falls and intracranial haemorrhage. However, evidence suggests that the absolute risk is low and outweighed by the reduction in stroke risk. DOACs are now recommended first line for most patients due to their favourable safety profile. Off-label dose reduction of DOACs is not recommended due to reduced efficacy with limited reduction in bleeding risk. Medication review and falls prevention strategies should be implemented before prescribing anticoagulation. Deprescribing should be considered in severe frailty, limited life expectancy and increased bleeding risk (e.g., cerebral microbleeds). CONCLUSION: When considering whether to (de-)prescribe anticoagulants, it is important to consider the risks associated with stopping therapy in addition to potential adverse events. Shared decision-making with the patient and their carers is crucial as patient and prescriber views often differ.

Treatment of Hypertension in People With Dementia: A Multicenter Prospective Observational Cohort Study.

OBJECTIVES: To describe the treatment of hypertension in people with dementia and collate evidence on adverse health events whilst on treatment. DESIGN: A multicenter prospective observational cohort study. SETTING AND PARTICIPANTS: People with documented diagnoses of hypertension and dementia were recruited through memory clinics and general practice from 8 sites in the United Kingdom. METHODS: The cohort was recruited between July 2013 and October 2014. Participants underwent face-to-face, standardized assessment of blood pressure (BP), activities of daily living, cognitive function, and medication use. Follow-up was by monthly telephone interview for 6 months to collate data on adverse health events. RESULTS: 181 participants were recruited and 177 followed up; 126 (70%) were female, mean age was 82 [standard deviation (SD) 6.3] years, median Mini-Mental State Examination score was 23 [interquartile range (IQR) 18-26] and mean BP was 141/78 (SD 22/12) mmHg. Antihypertensive drugs were prescribed in 157 (87%). Participants were prescribed a median of 1 (IQR 1-2) antihypertensive medication. Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were the most frequently prescribed antihypertensives in 63% of participants. Target BP was achieved in 58% (95% confidence interval 49%-64%). Increasing number of antihypertensives was not associated with lower systolic or diastolic BP, or with a higher proportion of patients attaining target BP. Participants had 214 falls, 3 had a fracture, 3 developed symptomatic heart failure, 4 had cerebrovascular events, and 8 died. CONCLUSIONS/IMPLICATIONS: In this population of people with mild dementia, participants were treated with standard antihypertensive medications in a similar proportion to the general population, with a similar proportion achieving target BP. The rate of adverse health events was higher than in randomized controlled trials of antihypertensives and raises reservations about the assumptions underpinning antihypertensive treatment in people with dementia. These findings may help inform clinical decision making.

Use of oral anticoagulants in older people with atrial fibrillation in UK general practice: protocol for a cohort study using the Clinical Practice Research Datalink (CPRD) database.

INTRODUCTION: Warfarin has frequently been underused in older people for stroke prevention in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) entered the UK market from 2008 and have been recommended as an alternative to warfarin. This study aimed to describe any changes in the prescribing of oral anticoagulants (OACs) to people aged ≥75 years in UK general practice before and after the introduction of DOACs, to examine differences in patient characteristics which may influence prescribers' decisions regarding anticoagulation, to evaluate the time people stay on OACs and switching between OACs. METHODS AND ANALYSIS: A retrospective cohort study design will be used. Patients with a diagnosis of AF will be identified from the Clinical Practice Research Datalink (CPRD). The study period will run from 1 January 2003 to 27 December 2017. Patients enter the cohort at the latest date of the start of the study period, first AF diagnosis, 75th birthday or a year from when they started to contribute research standard data. Follow-up continues until they leave the practice, death, the date the practice stops contributing research standard data or the end of the study period (27 December 2017). Exposure to OACs will be defined as ≥1 prescription issued for an OAC of interest during the study period. Patients issued an OAC in the year preceding study entry will be defined as 'prevalent users'. Patients starting on an OAC during the study period will be defined as 'incident users'. Incidence and prevalence of OAC prescribing, patient demographics and characteristics will be described during three time periods: 2003-2007, 2008-2012 and 2013-2017. Persistence (defined as the time from initiation to discontinuation of medication) with and switching between different OACs will be described. ETHICS AND DISSEMINATION: The protocol for this study was approved by the CPRD Independent Scientific Advisory Committee. The results will be disseminated in a peer-reviewed journal and at conferences. TRIAL REGISTRATION NUMBER: EUPAS29923.

Anticholinergic Drug Burden Tools/Scales and Adverse Outcomes in Different Clinical Settings: A Systematic Review of Reviews.

BACKGROUND: Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed. OBJECTIVE: This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them. METHODS: A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used. RESULTS: Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated. CONCLUSIONS: Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established.

Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer.

PURPOSE: The role played by the innate immune system in determining survival from non-small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC. METHODS: We used immunohistochemistry to identify tryptase+ mast cells and CD68+ macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC. RESULTS: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7.7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection. CONCLUSION: The tumor islet CD68+ macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study.