Ischaemic stroke in South Asians: The BRAINS study.

BACKGROUND AND PURPOSE: Studies on stroke in South Asian populations are sparse. The aim of this study was to compare differences in age of onset of ischaemic stroke in South Asian patients living in the United Kingdom and South Asian patients living in India versus White British stroke patients. METHODS: We studied the UK and Indian arms of the ongoing BRAINS study, an international prospective hospital-based study of South Asian stroke patients. The BRAINS study includes 4038 South Asian and White British patients with first-ever ischaemic stroke, recruited from sites in the United Kingdom and India. RESULTS: Of the included patients, 1126 were South Asians living in India (ISA), while 1176 were British South Asian (BSA) and 1736 were White British (WB) UK residents. Patients in the ISA and BSA groups experienced stroke 19.5 years and 7.2 years earlier than their WB counterparts, respectively (mean [interquartile range] age: BSA 64.3 [22] years vs. ISA 52.0 [18] years vs. WB 71.5 [19] years; p < 0.001). Patients in the BSA group had higher rates of hypertension, diabetes mellitus and hypercholesterolaemia than those in the ISA and WB groups. After adjustment for traditional stroke risk factors, an earlier age of stroke onset of 18.9 years (p < 0.001) and 8.9 years (p < 0.001) was still observed in the ISA and BSA groups, respectively. In multivariable stepwise linear regression analysis, ethnicity accounted for 24.7% of the variance in early age onset. CONCLUSION: Patients in the BSA and ISA groups experienced ischaemic stroke approximately 9 and 19 years earlier, respectively, than their WB counterparts. Ethnicity is an independent predictor of early age of stroke onset. Our study has considerable implications for public health policymakers in countries with sizable South Asian populations.

Hospital pharmacists' opinions on a risk prediction tool for medication-related harm in older people.

AIM: Older adults are particularly affected by medication-related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk-prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME-RPT. METHODS: Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case-vignettes each with a calculated PRIME-RPT score to help guide discussion. Case-vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a "framework" approach. RESULTS: Seven themes emerged in relation to the PRIME-RPT: (1) providing a medicine-prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow-up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations. CONCLUSION: Hospital pharmacists found the PRIME-RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.

Atrial fibrillation, transient ischaemic attack and stroke in older people. A themed collection in age and ageing journal.

With an increase in the ageing population, there is a rise in the burden of cardiovascular disease. Age and Ageing have compiled collections of their key cardiovascular themed papers. The first Age and Ageing Cardiovascular Collection focussed on blood pressure, coronary heart disease and heart failure. In this second collection, publications since 2011 were selected with emphasis on atrial fibrillation, transient ischaemic attack (TIA) and stroke. The prevalence of TIA and stroke increases as people get older. In this commentary we summarise studies published in Age and Ageing that bring to the fore the need for a multidisciplinary, person-centred approach to care, conscientious identification of risk factors and their management and prevention strategies, which will inform policy ultimately reducing the burden of cost placed by stroke care on healthcare financing. Read the latest Cardiovascular Collection here.

Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients.

PURPOSE: Sarcopenia is associated with poor outcomes, and evidence suggests an inverse relationship between skeletal muscle mass and cardiovascular risk. Sarcopenia has been studied after stroke, but its value as a risk factor for stroke has not been examined. This prospective cohort study measured sarcopenia in stroke/TIA patients at baseline to explore its role in predicting recurrent events. METHOD: The Arterial Stiffness In lacunar Stroke and TIA (ASIST) study included 96 patients with TIA/lacunar stroke, of which 82 patients (mean age 71.2±10.8 years) had bioimpedance analysis to assess body composition. Skeletal Mass Index (SMI) was calculated and parameters of sarcopenia assessed using Davison (1) and Janssen (2) criteria. Recurrent cerebrovascular events were monitored over 5 years. RESULTS: Eighteen patients had recurrent events. On independent samples t test there were significantly more participants with sarcopenia in the recurrent events group (89% vs 56%, p<0.001) using Davison (1) criteria, as well as lower mean SMI, significantly more participants with diabetes and higher arterial stiffness. On binary logistic regression, the only significant predictors of recurrent events were SMI (p=0.036, hazard ratio=0.414, 95% confidence interval 0.195-0.948) and diabetes (p=0.004, hazard ratio=9.06, 95% confidence interval 2.009-40.860) when corrected for age, sex and cardiovascular risk factors. Using Janssen (2) criteria in the regression, severe sarcopenia was a significant predictor of recurrent events (p=0.028). There was a significant association between sarcopenia and recurrent events on Chi square based on Davison (p=0.02) and Janssen (p=0.034) definitions. CONCLUSIONS: The presence of baseline sarcopenia in stroke and TIA patients is an independent predictor of recurrent events.

Age and ageing cardiovascular collection: blood pressure, coronary heart disease and heart failure.

As people age they are at increased risk of cardiovascular disease, the leading cause of mortality and morbidity worldwide. Understanding cardiovascular ageing is essential to preserving healthy ageing and preventing serious health outcomes. This collection of papers published in Age and Ageing since 2011 cover key themes in cardiovascular ageing, with a separate collection on stroke and atrial fibrillation planned. Treating high blood pressure remains important as people age and reduces strokes and heart attacks. That said, a more personalised approach to blood pressure may be even more important as people age to lower blood pressure to tight targets where appropriate but avoid overtreatment in vulnerable groups. As people age, more people experience blood pressure drops on standing (orthostatic hypotension), particularly as they become frail. This can predispose them to falls. The papers in this collection provide an insight into blood pressure and orthostatic hypotension. They highlight areas for further research to understand blood pressure changes and management in the ageing population. Inpatient clinical care of older people with heart attacks differs from younger people in UK national audit data. People aged over 80 had improved outcomes in survival after heart attack over time, but had lower rates of specialist input from cardiology compared with younger people. This may partly reflect different clinical presentations, with heart attacks occurring in the context of other health conditions, frailty and multimorbidity. The care and outcomes of acute and chronic cardiovascular disease are impacted by the frailty and health status of an individual at baseline. The research included in this collection reinforces the wide variations in the ageing population and the necessity to focus on the individual needs and priorities, and provide a person-centred multidisciplinary approach to care.

Characterising older adults' risk of harm from blood-pressure lowering medications: a sub-analysis from the PRIME study.

AIM: Cardiovascular disease (CVD) is common amongst frail older people. The evidence base for CVD commonly excludes older adults with multimorbidity or chronic conditions. Most cardiovascular drugs have the potential to lower blood pressure (BP) and therefore cause medication-related harm (MRH). We aimed to identify key clinical and sociodemographic characteristics associated with MRH in older people taking BP-lowering drugs for whatever indication they were prescribed. METHODS: The PRIME (prospective study to develop a model to stratify the risk of MRH in hospitalised elderly patients in the UK) study investigating the incidence and cost of MRH in older people across Southern England. Adults ≥65 years were recruited from five teaching hospitals at hospital discharge and followed up for 8 weeks. Telephone interviews with study participants, review of primary care records and hospital readmissions were undertaken to identify MRH. PRIME study participants taking BP-lowering drugs (as defined by National Institute for Health and Care Excellence hypertension guidelines) were included in this analysis. RESULTS: One hundred and four (12%) study patients experienced a total of 153 MRH events associated with BP-lowering drugs. Patients on four BP-lowering drugs were five times more likely to experience MRH compared to those taking one medication (OR 4.96; 95%CI 1.63-15.13; P = 0.01). Most MRH events were classified 'serious' (80%, n = 123), requiring dose change or treatment cessation. Almost half of MRH were potentially preventable (49%, n = 75). CONCLUSION: Polypharmacy from BP-lowering drugs in older people is associated with preventable harm. Decisions around cardiovascular risk reduction should be carefully considered in view of MRH arising from BP-lowering drugs.

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy.

OBJECTIVES: To determine the association between frailty and medication-related harm requiring healthcare utilisation. DESIGN: Prospective observational cohort study. SETTING: Six primary and five secondary care sites across South East England, September 2013-November 2015. PARTICIPANTS: One thousand and two hundred and eighty participants, ≥65 years old, who were due for discharge from general medicine and older persons' wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained. MAIN OUTCOME MEASURES: Medication-related harm requiring healthcare utilisation (including primary, secondary or tertiary care consultations related to MRH), including adverse drug reactions, non-adherence and medication error determined via the review of data from three sources: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of readmission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing number of medicines and frailty. RESULTS: Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06-49.26, P = 0.004), independent of age, gender, and number of medicines. With increasing frailty, the need for healthcare use as a result of MRH increases from a probability of around 0.2-0.4. This is also the case for the number of medicines. CONCLUSIONS: Frailty is associated with MRH, independent of polypharmacy. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.

Implementation of a medicine management plan (MMP) to reduce medication-related harm (MRH) in older people post-hospital discharge: a randomised controlled trial.

BACKGROUND: Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients. In this study, we aim to find out if a Medicines Management Plan (MMP) linked to the DMS is more effective than the DMS alone in reducing rates of MRH. METHOD: Using a randomized control trial design, 682 older adults ≥ 65 years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients' clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods. DATA ANALYSIS: Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners' understanding, and acceptance of the MMP, DMS and the RPT. CONCLUSION: This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Do the 2015 Beers Criteria predict medication-related harm in older adults? Analysis from a multicentre prospective study in the United Kingdom.

PURPOSE: To investigate whether inappropriate prescribing, defined by the Beers Criteria, is associated with medication-related harm (MRH), hospital admission, and mortality in older adults in England. METHODS: A multicentre, prospective cohort study recruited 1280 patients (median age 82 years) at hospital discharge. Patients were followed-up in the community by pharmacists for 8 weeks to identify MRH (harm from adverse drug reactions, non-adherence, and medication errors) and hospital admissions. One-year mortality was determined using hospital records. Potentially inappropriate medications (PIMs) were determined using the 2015 version of the Beers criteria. Logistic regression was used to investigate the relationship between patients prescribed PIMs and adverse outcomes. RESULTS: Two hundred and seventy-six patients (22%) were prescribed one or more PIMs at hospital discharge. The main PIM classes prescribed at hospital discharge were benzodiazepines and related drugs (30%) and antidepressants (27%). 1116 out of 1280 patients completed follow-up and 413 (37%) experienced MRH. In 51 cases (12%), MRH was attributable to a PIM. There was no significant relationship between patients prescribed PIMs and overall MRH, hospital readmission or all-cause one-year mortality. Multiple PIMs at discharge was independently associated with an increased risk of ADR (OR 2.32, 95% CI 1.03-5.23). CONCLUSION: The prescribing of PIMs is common at hospital discharge of older adults in England. The 2015 Beers criteria have a limited clinical value to predict adverse outcomes following hospital discharge in this setting.

Can doctors identify older patients at risk of medication harm following hospital discharge? A multicentre prospective study in the UK.

AIMS: Medication-related harm (MRH) is common in older adults following hospital discharge. In resource-limited health systems, interventions to reduce this risk can be targeted at high-risk patients. This study aims to determine whether (1) doctors can predict which older patients will experience MRH requiring healthcare following hospital discharge, (2) clinical experience and confidence in prediction influence the accuracy of the prediction. METHODS: This was a multicentre observational prospective study involving five teaching hospitals in England between September 2013 and November 2015. Doctors discharging patients (aged ≥65 years) from medical wards predicted the likelihood of their patient experiencing MRH requiring healthcare (hospital readmission or community healthcare) in the initial 8-week period post-discharge. Patients were followed up by senior pharmacists to determine MRH occurrence. RESULTS: Data of 1066 patients (83%) with completed predictions and follow-up, out of 1280 recruited patients, were analysed. Patients had a median age of 82 years (65-103 years), and 58% were female. Most predictions (85%) were made by junior doctors with less than 5 years' clinical experience. There was no relationship between doctors' predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective of years of clinical experience. Doctors' predictions were more likely to be accurate when they reported higher confidence in their prediction, especially in predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P < 0.001). CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to predict MRH in older adults post-discharge.

Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial.

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2-4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.

The Association between Arterial Stiffness, Initial Stroke Severity, and 3-Week Outcomes in Patients with Ischemic Stroke.

OBJECTIVES: Vascular compliance is emerging as a useful cardiovascular risk factor. The aim of this study was to investigate the association between arterial stiffness and stroke severity at presentation and 3 weeks. METHODS: Forty two patients with acute ischemic stroke (55% male, mean age 71 years) were recruited over 15-months. Stroke subtypes were classified into lacunar circulation infarct (LACI), partial anterior circulation infarct (PACI), and posterior circulation infarct (POCI). Arterial stiffness was measured by QKD (defined as the time interval between the appearance of the Q wave [Q] on the ECG and the arrival of the diastolic Korotkoff [K] sound over the brachial artery in diastole [D]; QKD It is measured in milliseconds) using 24-hour ambulatory blood pressure (BP) and electrocardiogram monitoring. The measured QKD values were then corrected for a heart rate of 60 bpm and a systolic BP of 100 mm Hg (QKD100-60). Stroke severity was assessed on admission and at 3 weeks using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Regression analysis for all patients showed a weak non-significant correlation between arterial stiffness and stroke severity. However, on performing subgroup analysis using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, we found that in large-artery atherosclerosis, arterial stiffness predicted stroke severity significantly at baseline (r = .45, b = .093, P = .04), but not significant for cardio embolism or small-artery occlusion subtypes. QKD100-60 and stroke severity were not significantly associated in week 3. There was no difference in NIHSS scores at weeks 0 and 3, or in QKD100-60 between LACI, PACI, and POCI, or dipper versus non-dippers and reverse dippers. CONCLUSION: Further research is needed to explore the association between QKD and stroke severity.

Protocol for a Prospective (P) study to develop a model to stratify the risk (RI) of medication (M) related harm in hospitalized elderly (E) patients in the UK (The PRIME study).

BACKGROUND: Medication related harm (MRH) is a common cause of morbidity and hospital admission in the elderly, and has significant cost implications for both primary and secondary healthcare resources. The development of risk prediction models has become an increasingly common phenomenon in medicine and can be useful to guide objective clinical decision making, resource allocation and intervention. There are no risk prediction models that are widely used in clinical practice to identify elderly patients at high risk of MRH following hospital discharge. The aim of this study is to develop a risk prediction model (RPM) to identify elderly patients at high risk of MRH upon discharge from hospital, and to compare this with routine clinical judgment. METHODS/DESIGN: This is a multi-centre, prospective observational study following a cohort of patients for 8 weeks after hospital discharge. Data collection including patient characteristics, medication use, social factors and frailty will take place prior to patient discharge and then the patient will be followed up in the community over the next 8 weeks to determine if they have experienced MRH. Research pharmacists will determine whether patients have experienced MRH by prospectively reviewing records for unplanned emergency department attendance, hospital readmission and GP consultation related to MRH. Research pharmacists will also telephone patients directly to determine self-reported MRH, which patients may not have sought further medical attention for. The data collected will inform the development of a RPM which will be externally validated in a follow-up study. DISCUSSION: There are no RPMs that are used in clinical practice to help stratify elderly patients at high risk of MRH in the community following hospital discharge, despite this being a significant public health problem. This study plans to develop a clinically useful RPM that is better than routine clinical judgment. As this is a multi-centre study involving clinical settings that serve elderly people of heterogeneous sociodemographic background, it is anticipated that this RPM will be generalizable.