Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

Does self-monitoring reduce blood pressure? Meta-analysis with meta-regression of randomized controlled trials

Introduction. Self-monitoring of blood pressure (BP) is an increasingly common part of hypertension management. The objectives of this systematic review were to evaluate the systolic and diastolic BP reduction, and achievement of target BP, associated with self-monitoring. Methods. MEDLINE, Embase, Cochrane database of systematic reviews, database of abstracts of clinical effectiveness, the health technology assessment database, the NHS economic evaluation database, and the TRIP database were searched for studies where the intervention included self-monitoring of BP and the outcome was change in office/ambulatory BP or proportion with controlled BP. Two reviewers independently extracted data. Meta-analysis using a random effects model was combined with meta-regression to investigate heterogeneity in effect sizes. Results. A total of 25 eligible randomized controlled trials (RCTs) (27 comparisons) were identified. Office systolic BP (20 RCTs, 21 comparisons, 5,898 patients) and diastolic BP (23 RCTs, 25 comparisons, 6,038 patients) were significantly reduced in those who self-monitored compared to usual care (weighted mean difference (WMD) systolic −3.82 mmHg (95% confidence interval −5.61 to −2.03), diastolic −1.45 mmHg (−1.95 to −0.94)). Self-monitoring increased the chance of meeting office BP targets (12 RCTs, 13 comparisons, 2,260 patients, relative risk = 1.09 (1.02 to 1.16)). There was significant heterogeneity between studies for all three comparisons, which could be partially accounted for by the use of additional co-interventions. Conclusion. Self-monitoring reduces blood pressure by a small but significant amount. Meta-regression could only account for part of the observed heterogeneity

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

Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population.

Background Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. Study design A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire. 1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa). The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication

Floral and insect-induced volatile formation in Arabidopsis lyrata ssp. petraea, a perennial, outcrossing relative of A. thaliana

Volatile organic compounds have been reported to serve some important roles in plant communication with other organisms, but little is known about the biological functions of most of these substances. To gain insight into this problem, we have compared differences in floral and vegetative volatiles between two closely related plant species with different life histories. The self-pollinating annual, Arabidopsis thaliana, and its relative, the outcrossing perennial, Arabidopsis lyrata, have markedly divergent life cycles and breeding systems. We show that these differences are in part reflected in the formation of distinct volatile mixtures in flowers and foliage. Volatiles emitted from flowers of a German A. lyrata ssp. petraea population are dominated by benzenoid compounds in contrast to the previously described sesquiterpene-dominated emissions of A. thaliana flowers. Flowers of A. lyrata ssp. petraea release benzenoid volatiles in a diurnal rhythm with highest emission rates at midday coinciding with observed visitations of pollinating insects. Insect feeding on leaves of A. lyrata ssp. petraea causes a variable release of the volatiles methyl salicylate, C11- and C16-homoterpenes, nerolidol, plus the sesquiterpene (E)-β-caryophyllene, which in A. thaliana is emitted exclusively from flowers. An insect-induced gene (AlCarS) with high sequence similarity to the florally expressed (E)-β-caryophyllene synthase (AtTPS21) from A. thaliana was identified from individuals of a German A. lyrata ssp. petraea population. Recombinant AlCarS converts the sesquiterpene precursor, farnesyl diphosphate, into (E)-β-caryophyllene with α-humulene and α-copaene as minor products indicating its close functional relationship to the A. thaliana AtTPS21. Differential regulation of these genes in flowers and foliage is consistent with the different functions of volatiles in the two Arabidopsis species

Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial

BACKGROUND: Exercise has been shown to be beneficial for selected patients with heart failure, but questions remain over its effectiveness, cost-effectiveness and uptake in a real world setting. This paper describes the design, rationale and recruitment for a randomised controlled trial that will explore the effectiveness and uptake of a predominantly home-based exercise rehabilitation programme, as well as its cost-effectiveness and patient acceptability. METHODS/DESIGN: Randomised controlled trial comparing specialist heart failure nurse care plus a nurse-led predominantly home-based exercise intervention against specialist heart failure nurse care alone in a multiethnic city population, served by two NHS Trusts and one primary care setting, in the United Kingdom. 169 English speaking patients with stable heart failure, defined as systolic impairment (ejection fraction ≤ 40%). with one or more hospital admissions with clinical heart failure or New York Heart Association (NYHA) II/III within previous 24-months were recruited. Main outcome measures at 1 year: Minnesota Living with Heart Failure Questionnaire, incremental shuttle walk test, death or admission with heart failure or myocardial infarction, health care utilisation and costs. Interviews with purposive samples of patients to gain qualitative information about acceptability and adherence to exercise, views about their treatment, self-management of their heart failure and reasons why some patients declined to participate. The records of 1639 patients managed by specialist heart failure services were screened, of which 997 (61%) were ineligible, due to ejection fraction>40%, current NYHA IV, no admission or NYHA II or more within the previous 2 years, or serious co-morbidities preventing physical activity. 642 patients were contacted: 289 (45%) declined to participate, 183 (39%) had an exclusion criterion and 169 (26%) agreed to randomisation. DISCUSSION: Due to safety considerations for home-exercise less than half of patients treated by specialist heart failure services were eligible for the study. Many patients had co-morbidities preventing exercise and others had concerns about undertaking an exercise programme

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals

BackgroundThe precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata.Methods and findingsA systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%–1.82%) and 0.41% (95% CI, 0.31%–0.53%) for &lt;65-year-olds. New AF detection rate increased progressively with age from 0.34% (&lt;60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (&lt;60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60–64 years; and 1,089 for &lt;60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples.ConclusionsPeople with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and &gt;70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations

Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

Abstract Background Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p Conclusion Once eligible for this trial, people from different ethnic groups were recruited in similar proportions. The reason for ineligibility in the BRUM study was the inability to support the range of minority languages.</p

Development and initial validation of a simple clinical decision tool to predict the presence of heart failure in primary care:The MICE (Male, Infarction, Crepitations, Edema) rule

Aims: Diagnosis of heart failure in primary care is often inaccurate, and access to and use of echocardiography is suboptimal. This study aimed to develop and provisionally validate a clinical prediction rule to optimize referral for echocardiography of people identified in primary care with suspected heart failure. Methods and results: A systematic review identified studies of diagnosis of heart failure set in primary care. The individual patient data for five of these studies were obtained. Logistic regression models to predict heart failure were developed on one of the data sets and validated on the others using area under the receiver operating characteristic curve (AUROC), and goodness-of-fit calibration plots. A model based upon four simple clinical features (Male, history of myocardial Infarction, Crepitations, Edema: MICE) and natriuretic peptide had good validity when applied to other data sets, with AUROCs between 0.84 and 0.93, and reasonable calibration. The rule performed well across the data sets, with sensitivity between 81 and 96 and specificity between 57 and 74.Conclusions: A simple clinical rule based upon gender, history of myocardial infarction, presence of ankle oedema, and presence of basal lung crepitations can discriminate between people with suspected heart failure who should be referred straight for echocardiography and people for whom referral should depend upon the result of a natriuretic peptide test. Prospective validation and an implementation evaluation of the rule is now warranted